A Phase 3 Randomized Trial of Inotuzumab Ozogamicin (IND#:133494, NSC#: 772518) for Newly Diagnosed High-Risk B-ALL; Risk-Adapted Post-Induction Therapy for High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and Disseminated B-LLy
Conditions: Leukemia
Eligibility: B-ALL and MPAL patients must be enrolled on APEC14B1 and consented to eligibility studies (Part A) prior to treatment and enrollment on AALL1732. Note that central confirmation of MPAL diagnosis must occur within 22 days of enrollment for suspected MPAL patients. If not performed within this time frame, patients will be taken off protocol.
APEC14B1 is not a requirement for B-LLy patients but for institutional compliance every patient should be offered participation in APEC14B1. B-LLy patients may directly enroll on AALL1732.
Patients must be > 365 days and < 25 years of age
White blood cell count (WBC) criteria for patients with B-ALL (within 7 days prior to the start of protocol-directed systemic therapy):
Age 1-9.99 years: WBC >= 50,000/uL
Age 10-24.99 years: Any WBC
Age 1-9.99 years: WBC < 50,000/uL with:
Testicular leukemia
CNS leukemia (CNS3)
Steroid pretreatment.
White blood cell count (WBC) criteria for patients with MPAL (within 7 days prior to the start of protocol-directed systemic therapy):
Age 1-24.99 years: any WBC NOTE: Patients enrolled as suspected MPAL but found on central confirmatory testing to have B-ALL must meet the B-ALL criteria above (age, WBC, extramedullary disease, steroid pretreatment) to switch to the B-ALL stratum before the end of induction.
Patient has newly diagnosed B-ALL or MPAL (by World Health Organization [WHO] 2016 criteria) with >= 25% blasts on a bone marrow (BM) aspirate;
OR If a BM aspirate is not obtained or is not diagnostic of acute leukemia, the diagnosis can be established by a pathologic diagnosis of acute leukemia on a BM biopsy;
OR A complete blood count (CBC) documenting the presence of at least 1,000/uL circulating leukemic cells if a bone marrow aspirate or biopsy cannot be performed.
Patient has newly diagnosed B-LLy Murphy stages III or IV.
Patient has newly diagnosed B-LLy Murphy stages I or II with steroid pretreatment.
Note: For B-LLy patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to B-ALL. For tissue processed by other means (i.e., paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of B-LLy defined by the submitting institution will be accepted.
Central nervous system (CNS) status must be determined prior to enrollment based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment and cytoreduction. It is recommended that intrathecal cytarabine be administered at the time of the diagnostic lumbar puncture. This is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture. This is allowed prior to enrollment. Systemic chemotherapy must begin within 72 hours of this intrathecal therapy.
All patients and/or their parents or legal guardians must sign a written informed consent.
All institutional, Food and Drug Administration (FDA), and NCI requirements for human studies must be met.
Principal Investigator: Maggie Fader
Learn more at https://clinicaltrials.gov/study/NCT03959085.
Stopping Tyrosine Kinase Inhibitors (TKI) to Assess Treatment-Free Remission (TFR) in Pediatric Chronic Myeloid Leukemia - Chronic Phase (CML-CP)
Conditions: Leukemia
Principal Investigator: Maggie Fader
Learn more at https://clinicaltrials.gov/study/NCT03817398.
A Phase 3 Randomized Trial for Patients with De Novo AML Comparing Standard Therapy Including Gemtuzumab Ozogamicin (GO) to CPX-351 with GO, and the Addition of the FLT3 Inhibitor Gilteritinib for Patients with FLT3 Mutations
Conditions: Leukemia
Principal Investigator: Maggie Fader
Learn more at https://clinicaltrials.gov/study/NCT04293562.
An Open-Label Feasibility Study to Assess the Safety and Pharmacokinetics of Enasidenib in Pediatric Patients with Relapsed/Refractory Acute Myeloid Leukemia R/R-AML with an Isocitrate Dehydrogenase-2 IDH2 Mutation
Conditions: Leukemia
Eligibility: Patients must be >= 24 months and < 21 years of age at the time of study enrollment
Patient must have AML with an IDH2 mutation identified from a peripheral blood or bone marrow sample at the time of diagnosis and/or relapsed/refractory disease
Patient must have bone marrow assessment (aspiration or biopsy) with > 5% leukemic blasts by morphology and/or flow cytometry in at least one of the following clinical scenarios:
Second or greater relapse after chemotherapy or hematopoietic stem cell transplant (HSCT)
Refractory after >= 2 attempts at induction therapy
Relapsed patients
Must not have received prior re-induction therapy for this relapse
Each block of chemotherapy (i.e., cytarabine, daunorubicin and etoposide [ADE], cytarabine and mitoxantrone [MA]) is a separate re-induction attempt
Donor lymphocyte infusion (DLI) is considered a re-induction attempt
Refractory patients
Each attempt at induction therapy may include up to two chemotherapy courses
Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
Evaluation of cerebrospinal fluid (CSF) is only required if there is a clinical suspicion of central nervous system (CNS) involvement by leukemia during eligibility screening. Should a patient be found to have CNS2 or CNS3 status by CSF prior to eligibility screening, patient may receive intrathecal chemotherapy > 72 hours prior to starting study drug. CNS1 status must be established before starting study drug
Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately
Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive. The duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
>= 14 days must have elapsed after the completion of other cytotoxic therapy with the exception of hydroxyurea. Additionally, patients must have fully recovered from all acute toxic effects of prior therapy. NOTE: Cytoreduction with hydroxyurea must be discontinued >= 24 hours prior to the start of protocol therapy
Intrathecal chemotherapy must be completed >= 72 hours prior to the start of the first cycle of treatment
Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent. The duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair and the study research coordinator
Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
Stem cell Infusions (with or without total body irradiation [TBI]):
Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion:
>= 60 days after infusion for bone marrow or stem cell transplant and
>= 4 weeks after infusion for any stem cell infusion including DLI or boost infusion
There must be no evidence of graft versus host disease (GVHD)
Autologous stem cell infusion including boost infusion: >= 42 days
Cellular Therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
XRT/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-metaiodobenzylguanidine [MIBG]): >= 42 days after systemically administered radiopharmaceutical therapy
Study-specific limitations on prior therapy: small molecule investigational agents: >= 14 days or > 5 half-lives must have elapsed from the last dose of the agent, whichever is greater
Platelet count >= 20,000/mm^3 (may receive platelet transfusions)
Hemoglobin >= 8.0 g/dL at baseline (may receive red blood cell [RBC] transfusions)
Creatinine clearance or radioisotope glomerular filtration rate [GFR] >= 70 ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
Age: Maximum serum creatinine (mg/dL)
2 to < 6 years: 0.8 (male and female)
6 to < 10 years: 1 (male and female)
10 to < 13 years: 1.2 (male and female)
13 to < 16 years: 1.5 (male); 1.4 (female)
>= 16 years: 1.7 (male); 1.4 (female)
Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 225 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L
Serum albumin >= 2 g/dL
Left ventricular ejection fraction of >= 50% by echocardiogram
Principal Investigator: Maggie Fader
Learn more at https://clinicaltrials.gov/study/NCT04203316.
Pediatric Acute Leukemia (PedAL) Screening Trial – Developing New Therapies for Relapsed Leukemias
Conditions: Leukemia
Eligibility: Patients must be less than 22 years of age at the time of study enrollment
Patient must have one of the following at the time of study enrollment:
Patient has known or suspected relapsed/refractory (including primary refractory) AML as defined in protocol
- This includes isolated myeloid sarcoma
Patient has known or suspected relapsed/refractory (including primary refractory) myeloid leukemia of Down syndrome (ML-DS)
Patient has known or suspected relapsed ALL as defined in protocol that meets one of the following criteria:
- Second or greater B-ALL medullary relapse, excluding KMT2Ar - Any first or greater B-ALL medullary relapse involving KMT2Ar - Any first or greater T-ALL medullary relapse with or without KMT2Ar
Patient has known or suspected relapsed/refractory (including primary refractory) mixed phenotype acute leukemia (MPAL) as defined in protocol
Patient has known or suspected de novo or relapsed/refractory (including primary refractory) treatment-related AML (t-AML)
Patient has known or suspected de novo or relapsed/refractory (including primary refractory) myelodysplastic syndrome (MDS) or treatment-related myelodysplastic syndrome (t-MDS)
- Note: Relapsed/refractory disease includes stable disease, progressive disease, and disease relapse.
Patient has known or suspected de novo or relapsed/refractory (including primary refractory) juvenile myelomonocytic leukemia (JMML)
- Note: Relapsed/refractory disease includes stable disease, progressive disease, and disease relapse.
All patients and/or their parents or legal guardians must sign a written informed consent
All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Principal Investigator: Maggie Fader
Learn more at https://clinicaltrials.gov/study/NCT04726241.
A Phase 2 Study of Dabrafenib (NSC# 763760) with Trametinib (NSC# 763093) after Local Irradiation in Newly-Diagnosed BRAFV600-Mutant High-Grade Glioma (HGG)
Conditions: Glioma
Principal Investigator: Maggie Fader
Learn more at https://pubmed.ncbi.nlm.nih.gov/34838156/.
A Phase 3 Randomized Study of Selumetinib (IND # 77782) versus Carboplatin/Vincristine in Newly Diagnosed or Previously Untreated Neurofibromatosis Type 1 (NF1) Associated Low-Grade Glioma (LGG)
Conditions: Glioma
Principal Investigator: Ziad Khatib
Learn more at https://clinicaltrials.gov/study/NCT03871257.
A Phase 3 Randomized Non-Inferiority Study of Carboplatin and Vincristine versus Selumetinib (NSC# 748727, IND# 77782) in Newly Diagnosed or Previously Untreated Low-Grade Glioma (LGG) not associated with BRAFV600E Mutations or Systemic Neurofibromatosis Type 1 (NF1)
Conditions: Glioma
Eligibility: Patients must be >= 3 years and < 30 years at the time of study enrollment
- Patients must be newly diagnosed with localized primary CNS NGGCT of the suprasellar
and/or pineal region by pathology and/or serum or cerebrospinal fluid (CSF)
elevation of AFP above institutional normal or > 10 ng/mL or human chorionic
gonadotropin (hCG) beta > 100 mIU/mL as confirmed by Rapid Central Marker Screening
Review on APEC14B1-CNS. Suprasellar, pineal and bifocal tumors are included. (CSF
tumor markers and cytology must be within 31 days prior to enrollment and start of
protocol therapy [repeat if necessary]. Serum tumor markers, AFP and hCGbeta must be
within 7 days prior to enrollment and start of protocol therapy [repeat if
necessary]). Basal ganglia or other primary sites are excluded
- Patients with any of the following pathological elements are eligible: endodermal
sinus (yolk sac), embryonal carcinoma, choriocarcinoma, malignant/immature teratoma
and mixed germ cell tumor (GCT) (i.e., may include some pure germinoma) if malignant
elements listed above are present. Patients with only mature teratoma are excluded.
Patients with pure germinoma admixed with mature teratoma are excluded (would be
eligible for pure germinoma protocols)
- Patients must have a cranial MRI with and without gadolinium at diagnosis/prior to
enrollment. If surgical resection is performed, patients must have pre-operative and
post operative brain MRI with and without gadolinium. The post operative brain MRI
should be obtained within 72 hours of surgery. If patient has a biopsy only,
post-operative brain MRI is recommended but not required (within 31 days prior to
study enrollment and start of protocol therapy )
- Patients must have a spine MRI with gadolinium obtained at diagnosis/prior to
enrollment. Spine MRI with and without gadolinium is recommended (within 31 days
prior to study enrollment and start of protocol therapy)
- Lumbar CSF must be obtained prior to study enrollment unless medically
contraindicated. If a patient undergoes surgery and lumbar CSF cytology cannot be
obtained at the time of surgery, then it should be performed at least 10 days
following surgery and prior to study enrollment. False positive cytology can occur
within 10 days of surgery
- Patients must have RAPID CENTRAL TUMOR MARKER REVIEW CSF tumor markers obtained
prior to enrollment unless medically contraindicated. Ventricular CSF obtained at
the time of CSF diversion procedure (if performed) is acceptable for tumor markers
but lumbar CSF is preferred. In case CSF diversion and biopsy/surgery are combined,
CSF tumor markers should be collected first
- Peripheral absolute neutrophil count (ANC) >= 1000/uL (within 7 days prior to
enrollment)
Principal Investigator: Ziad Khatib
Learn more at https://www.cancer.gov/research/participate/clinical-trials-search/v?id=NCT04166409&r=1.
A Phase 3 Randomized, Placebo-Controlled Trial Evaluating Memantine (IND# 149832) for Neurocognitive Protection in Children Undergoing Cranial Radiotherapy as Part of Treatment for Primary Central Nervous System Tumors
Conditions: Central Nervous System Tumors
Principal Investigator: Ziad Khatib
Learn more at https://clinicaltrials.gov/study/NCT04939597.
A Phase 2 Trial of Chemotherapy followed by Response-Based Whole Ventricular & Spinal Canal Irradiation (WVSCI) for Patients with Localized Non-Germinomatous Central Nervous System Germ Cell Tumor
Conditions: Central Nervous System Tumors
Principal Investigator: Ziad Khatib
Learn more at https://clinicaltrials.gov/study/NCT04684368.
A Phase 3 Study of Sodium Thiosulfate for Reduction of Cisplatin-Induced Ototoxicity in Children with Average-Risk Medulloblastoma and Reduced Therapy in Children with Medulloblastoma with Low-Risk Features
Conditions: Medulloblastoma
Eligibility: PRE-ENROLLMENT: Patients must be greater than or equal to 3 years and less than 22 years of age at the time of enrollment on Step 0
PRE-ENROLLMENT: Patient is suspected to have newly-diagnosed medulloblastoma by institutional diagnosis
Principal Investigator: Ziad Khatib
Learn more at https://clinicaltrials.gov/study/NCT05382338.
A Phase 3 Randomized Controlled Trial Comparing Open vs Thoracoscopic Management of Pulmonary Metastases in Patients with Osteosarcoma
Conditions: Sarcoma
Eligibility: Patients must be < 40 years of age at the time of enrollment.
Patients must have a body surface area of >= 0.8 m^2 at the time of enrollment.
Patients must have histologic diagnosis (by institutional pathologist) of newly diagnosed high grade osteosarcoma. Primary tumors of all extremity and axial sites are eligible as long as diagnosis of high-grade osteosarcoma is established. Osteosarcoma as a second malignancy is eligible if no prior exposure to systemic chemotherapies.
Feasibility Phase:
Patients must have metastatic disease and a resectable primary tumor. Designation of a primary tumor as resectable will be determined at the time of diagnosis by the institutional multidisciplinary team.
For this study, metastatic disease is defined as one or more of the following:
Lesions which are discontinuous from the primary tumor, are not regional lymph nodes, and do not share a bone or body cavity with the primary tumor. Skip lesions in the same bone as the primary tumor do not constitute metastatic disease. Skip lesions in an adjacent bone are considered bone metastases.
Lung metastases: defined as biopsy-proven metastasis or the presence of one or more pulmonary lesions >= 5 mm, OR multiple pulmonary lesions >= 3 mm or greater in size.
Bone metastases: Areas suspicious for bone metastasis based on fludeoxyglucose F-18 (18F-FDG)-positron emission tomography (PET) scan (or whole body technetium-99 bone scan if 18F-FDG-PET is unavailable at the treating institution) require confirmatory biopsy or supportive anatomic imaging of at least one suspicious site with either magnetic resonance imaging (MRI) or computed tomography (CT) (whole body 18F-FDG-PET/CT or 18F-FDG-PET/MR scans are acceptable).
Principal Investigator: Ziad Khatib
Learn more at https://clinicaltrials.gov/study/NCT05235165.
A Feasibility and Randomized Phase 2/3 Study of the VEFGR2/MET Inhibitor Cabozantinib in Combination with Cytotoxic Chemotherapy for Newly Diagnosed Osteosarcoma
Conditions: Sarcoma
Principal Investigator: Ziad Khatib
Learn more at https://clinicaltrials.gov/study/NCT05691478.
A Prospective Phase 3 Study of Patients with Newly Diagnosed Very Low-risk and Low-risk Fusion Negative Rhabdomyosarcoma
Conditions: Sarcoma
Eligibility: All patients must be enrolled on APEC14B1 (NCT02402244) and consented to the Molecular Characterization Initiative (Part A) prior to enrollment and treatment on ARST2032 (this trial).
Patients must be =< 21 years at the time of enrollment.
Patients must have newly diagnosed embryonal rhabdomyosarcoma (ERMS), spindle cell/sclerosing RMS, or FOXO1 fusion negative alveolar rhabdomyosarcoma (ARMS) (institutional FOXO1 fusion results are acceptable). RMS types included under ERMS include those classified in the 1995 International Classification of Rhabdomyosarcoma (ICR) as ERMS (classic, spindle cell, and botryoid variants), which are reclassified in the 2020 World Health Organization (WHO) classification as ERMS (classic, dense and botryoid variants) and spindle cell/sclerosing RMS (encompassing the historical spindle cell ERMS variant and the newly recognized sclerosing RMS variant). Enrollment in APEC14B1 is required for all patients.
All patients will be evaluated for stage and clinical group. Note that clinical group designation assigned at the time of enrollment on study remains unchanged regardless of any second-look operation that may be performed.
Patients will be eligible for the very low-risk stratum (Regimen VA) if they have Stage 1, CG I disease.
Patients will be eligible for the low-risk stratum (Regimen VAC/VA) if they have Stage 1, CG II disease, Stage 2, CG I or II disease, or Stage 1, CG III (orbit only) disease.
Paratesticular Tumors: Staging ipsilateral retroperitoneal lymph node sampling (SIRLNS) is required for all patients >= 10 years of age with paratesticular tumors who do not have gross nodal involvement on imaging.
Extremity Tumors: Regional lymph node sampling is required for histologic evaluation in patients with extremity tumors.
Clinically or radiographically enlarged nodes must be sampled for histologic evaluation.
Patients must have a Lansky (for patients =< 16 years of age) or Karnofsky (for patients > 16 years of age) performance status score of >= 50. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing performance score.
Peripheral absolute neutrophil count (ANC) >= 750/uL (within 7 days prior to enrollment).
Platelet count >= 75,000/uL (transfusion independent) (within 7 days prior to enrollment).
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine (within 7 days prior to enrollment) based on age/gender as follows:
Age: 1 month to < 6 months; Maximum serum creatinine (mg/dL): 0.4 (male) : 0.4 (female)
Age: 6 months to < 1 year; Maximum serum creatinine (mg/dL): 0.5 (male) : 0.5 (female)
Age: 1 to < 2 years; Maximum serum creatinine (mg/dL): 0.6 (male) : 0.6 (female)
Age: 2 to < 6 years; Maximum serum creatinine (mg/dL): 0.8 (male) : 0.8 (female)
Age: 6 to < 10 years; Maximum serum creatinine (mg/dL): 1 (male) : 1 (female)
Age: 10 to < 13 years; Maximum serum creatinine (mg/dL): 1.2 (male) : 1.2 (female)
Age: 13 to < 16 years; Maximum serum creatinine (mg/dL): 1.5 (male) : 1.4 (female)
Age >= 16 years; Maximum serum creatinine (mg/dL): 1.7 (male) : 1.4 (female)
Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment), and
If there is evidence of biliary obstruction by the tumor, then the total bilirubin must be < 3 x ULN for age.
Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L.
Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L
If there is evidence of biliary obstruction by the tumor, then the total bilirubin must be < 3 x ULN for age
Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
All patients and/or their parents or legal guardians must sign a written informed consent.
All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.
Principal Investigator: Maggie Fader
Learn more at https://clinicaltrials.gov/study/NCT05304585.
A Phase 3 Study of Active Surveillance for Low risk and a Randomized Trial of Carboplatin vs. Cisplatin for Standard Risk Pediatric and Adult Patients with Germ Cell Tumors
Conditions: Germ Cell Tumor
Eligibility: There is no age limit for the low risk stratum (stage I ovarian immature teratoma and stage I non-seminoma or seminoma malignant GCT [all sites])
Standard risk 1: Patients must be < 11 years of age at enrollment
Standard risk 2: Patients must be >= 11 and < 25 years of age at enrollment
Patients enrolling on one of the low risk arms must be newly diagnosed with a stage I germ cell tumor; for the standard risk arms, patients must be newly diagnosed with metastatic germ cell tumor (stage II or higher); histologic confirmation of a primary extracranial germ cell tumor in any of the categories outlined below is required of all patients at enrollment except for those who were initially diagnosed with stage I non-seminoma malignant GCT and later recur during observation post surgery off study; for these patients, if elevated tumor markers rise to > 5 x upper limit of normal (ULN) on at least 2 measurements taken at least 1 week apart, a diagnostic biopsy is not required for enrollment
Low risk stage I immature teratoma (IT); site: ovarian; stage: Children's Oncology Group (COG) stage I, Federation of Gynecology and Obstetrics (FIGO) stage IA and IB; grade: 2 or 3; histology: pure immature teratoma (may contain microscopic foci of yolk sac tumor), mixed immature and mature teratoma, (no pathological evidence of MGCT); tumor markers: alpha-FP =< 1,000 ng/mL, beta-HCG institutional normal; all ages
Low risk stage I non-seminoma MGCT; site: ovarian, testicular, or extragonadal; stage: COG stage I, FIGO stage IA and IB, American Joint Committee on Cancer (AJCC) testicular stage IA, IB and IS; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma (pure or mixed); all ages
Low risk stage I seminoma-MGCT; site: testicular; stage: COG stage I; AJCC testicular stage IA IB, and IS; histology: may contain immature/mature teratoma; may NOT contain yolk sac tumor, embryonal carcinoma, or choriocarcinoma; all ages
Standard risk 1 (SR1); site: ovarian, testicular, or extragonadal; stage: COG stage II-IV, FIGO stage IC, FIGO stage II-IV (International Germ Cell Consensus Classification [IGCCC] criteria DO NOT apply); histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) < 11
Standard risk 2 (SR2)
Site: ovarian; stage: COG stage II and III, FIGO stage IC, II and III; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) >= 11 and < 25
Site: testicular; stage: COG stage II-IV, AJCC stage II, III, IGCCC good risk; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; tumor markers: must be IGCCC good risk; post op: alpha-FP < 1,000 ng/mL, beta-HCG < 5,000 IU/mL and lactate dehydrogenase (LDH) < 3.0 x normal; age (years) >= 11 and < 25
Site: extragonadal; stage: COG stage II; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) >= 11 and < 25
Principal Investigator: Maggie Fader
Learn more at https://clinicaltrials.gov/study/NCT03067181.
Phase 3 Accelerated BEP Trial: A Randomized Phase 3 Trial of Accelerated Versus Standard BEP Chemotherapy for Patients With Intermediate and Poor-Risk Metastatic Germ Cell Tumors
Conditions: Germ Cell Tumor
Eligibility: Age ≥ 11 years and ≤ 45 years on the date of randomisation
Histologically or cytologically confirmed germ cell tumour (non-seminoma or seminoma); or Exceptionally raised tumour markers (AFP ≥ 1000ng/mL and/or HCG ≥ 5000 IU/L) without histologic or cytologic confirmation in the rare case where pattern of metastases consistent with GCT, high tumour burden, and a need to start therapy urgently
Primary arising in testis, ovary, retro-peritoneum, or mediastinum
Metastatic disease or non-testicular primary
Intermediate or poor prognosis as defined by IGCCC classification3 (modified with different LDH criteria for intermediate risk non-seminoma, and inclusion of ovarian primaries). (See protocol for more information).
Adequate bone marrow function with ANC ≥1.0 x 10^9/L, Platelet count ≥100 x 10^9/L
Adequate liver function where bilirubin must be ≤1.5 x ULN, except participants with Gilbert's Syndrome where bilirubin must be ≤2.0 x ULN; ALT and AST must be ≤2.5 x ULN, except if the elevations are due to hepatic metastases, in which case ALT and AST must be ≤ 5 x ULN
Adequate renal function with estimated creatinine clearance of ≥60 ml/min according to the Cockcroft-Gault formula, unless calculated to be < 60 ml/min or borderline in which case GFR should be formally measured, eg. with EDTA scan
Principal Investigator: Maggie Fader
Learn more at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6114870/.
Pediatric Hepatic Malignancy International Therapeutic Trial (PHITT) – Phase 2/3
Conditions: Hepatic Malignancy
Eligibility: Age ≥ 11 years and ≤ 45 years on the date of randomisation
Histologically or cytologically confirmed germ cell tumour (non-seminoma or seminoma); or Exceptionally raised tumour markers (AFP ≥ 1000ng/mL and/or HCG ≥ 5000 IU/L) without histologic or cytologic confirmation in the rare case where pattern of metastases consistent with GCT, high tumour burden, and a need to start therapy urgently
Primary arising in testis, ovary, retro-peritoneum, or mediastinum
Metastatic disease or non-testicular primary
Intermediate or poor prognosis as defined by IGCCC classification3 (modified with different LDH criteria for intermediate risk non-seminoma, and inclusion of ovarian primaries). (See protocol for more information).
Adequate bone marrow function with ANC ≥1.0 x 10^9/L, Platelet count ≥100 x 10^9/L
Adequate liver function where bilirubin must be ≤1.5 x ULN, except participants with Gilbert's Syndrome where bilirubin must be ≤2.0 x ULN; ALT and AST must be ≤2.5 x ULN, except if the elevations are due to hepatic metastases, in which case ALT and AST must be ≤ 5 x ULN
Adequate renal function with estimated creatinine clearance of ≥60 ml/min according to the Cockcroft-Gault formula, unless calculated to be < 60 ml/min or borderline in which case GFR should be formally measured, eg. with EDTA scan
Principal Investigator: Ziad Khatib
Learn more at https://clinicaltrials.gov/study/NCT03017326.
A Randomized Phase 3 Interim Response Adapted Trial Comparing Standard Therapy with Immuno-oncology Therapy for Children and Adults with Newly Diagnosed Stage I and II Classic Hodgkin Lymphoma
Conditions: Hodgkin's Lymphoma
Principal Investigator: Ziad Khatib
Learn more at https://clinicaltrials.gov/study/NCT05675410.
Treatment of Newly Diagnosed Diffuse Anaplastic Wilms Tumors (DAWT) and Relapsed Favorable Histology Wilms Tumors (FHWT)
Conditions: Wilms Tumor
Principal Investigator: Ziad Khatib
Learn more at https://clinicaltrials.gov/study/NCT04322318.
Prospective Cohort Study to Evaluate Immunologic Response Following COVID-19 Vaccination in Children, Adolescents and Young Adults with Cancer
Conditions: Childhood Cancer
Eligibility: A patient enrolling prior to their first COVID-19 vaccine dose is eligible only if it is feasible to collect required baseline study specimens within protocol mandated time period prior to the initial COVID-19 vaccine dose; or a patient who already received a COVID-19 vaccine is eligible only if feasible to collect at least one post-first-dose follow-up specimen (i.e., at minimum, collection of the 24m PFD follow-up specimen must be feasible as per timing requirements * Note: for this observational study, the vaccine timing and regimen will proceed according to local discretion. Patients enrolled prior to their first COVID-19 vaccine dose who do not receive initial vaccine dose within 3 months after enrollment will be taken off study
Principal Investigator: Ziad Khatib
Learn more at https://clinicaltrials.gov/study/NCT05228275.
Phase 2 Study of Tovorafenib (DAY101) in Relapsed and Refractory Langerhans Cell Histiocytosis
Conditions: Langerhans Cell Histiocytosis
Eligibility: 180 days- < 22 years (at time of study enrollment)
Patient must have a body surface area of ≥ 0.3 m^2
Patients with progressive, relapsed, or recurrent LCH with measurable disease at study entry
Patients must have had histologic verification of LCH (from either original diagnosis or relapse/progression) at the time of study entry (must be obtained within 28 days prior to enrollment and start of protocol therapy) (repeat if necessary)
Tissue confirmation of relapse is recommended but not required
Pathology report must be submitted for central confirmation of diagnosis within 7 days of enrollment.
Formalin-fixed paraffin-embedded (FFPE) blocks or unstained slides (initial diagnosis and/or subsequent biopsies) will be required for retrospective central confirmation of diagnosis and molecular studies
Patients with mixed histiocytic disorders (e.g. LCH with juvenile xanthogranuloma) may be included
Patients must have measurable disease, documented by radiographic imaging (LCH- specific response criteria (must be obtained within 28 days prior to enrollment and start of protocol therapy) (repeat if necessary).
Patients must have progressive or refractory disease or experience relapse after at least one previous systemic treatment strategy
Pathogenic somatic mutation detected in genes encoding tyrosine kinase receptors (CSFR1, ERBB3 or ALK), RAS or RAF (may be from original or subsequent biopsy or peripheral blood/bone marrow aspirate). Clinical mutation reports may include quantitative polymerase chain reaction (PCR) (e.g. BRAFV600E) and/or Sanger or next generation sequencing. Immunohistochemistry (e.g. VE1 antibody for BRAFV600E) alone is not sufficient
Participant must be able to take an enteral dose and formulation of medication. Study medication is only available as an oral suspension or tablet, which may be taken by mouth or other enteral route such as nasogastric, jejunostomy, or gastric tube
Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50% for patients =< 16 years of age
Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
Myelosuppressive chemotherapy: Patients must not have received within 14 days of entry onto this study
Investigational agent or any other anticancer therapy not defined above: Patients must not have received any investigational agent or any other anticancer therapy (including MAPK pathway inhibitor) for at least 14 days prior to planned start of tovorafenib (DAY101)
Radiation therapy (RT): Patient must not have received RT within 2 weeks after the last dose fraction of RT
Patients must have fully recovered from any prior surgery
Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, targeted inhibitor, and/or radiotherapy with toxicities reduced to grade 1 or less (Common Terminology Criteria for Adverse Events [CTCAE] version 5.0)
Steroids: =< 0.5 mg/kg/day of prednisone equivalent (maximum 20 mg/day) averaged during the month prior to study enrollment is permissible
Strong inducers or inhibitors of CYP2C8 are prohibited for 14 days before the first dose of tovorafenib (DAY101) and from planned administration for the duration of study participation
Medications that are breast cancer resistant protein (BCRP) substrates that have a narrow therapeutic index are prohibited for 14 days before the first dose of tovorafenib (DAY101) and for the duration of study participation
Peripheral absolute neutrophil count (ANC) >= 750/uL unless secondary to bone marrow involvement, in such cases bone marrow involvement must be documented (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)
Platelet count >= 75,000/uL (unsupported/without transfusion within the past 7 days) (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)
Patients with marrow disease must have platelet count of >= 75,000/uL (transfusion support allowed) and must not be refractory to platelet transfusions. Bone marrow involvement must be documented
Hemoglobin >= 8 g/dL (unsupported/without transfusion within the past 7 days). Patients with marrow disease must have hemoglobin >= 8 g/dL (transfusion support allowed). Bone marrow involvement must be documented
Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g., Neulasta [registered trademark]) or 7 days for short-acting growth factor
A serum creatinine based on age/gender as follows (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)
Age: 6 months to < 1 year; Maximum Serum Creatinine (mg/dL):= 0.5 mg/dl (male and female)
Age: 1 to < 2 years; Maximum Serum Creatinine (mg/dL): = 0.6 mg/dl (male and female)
Age: 2 to < 6 years; Maximum Serum Creatinine (mg/dL): = 0.8 mg/dl (male and female)
Age: 6 to < 10 years; Maximum Serum Creatinine (mg/dL): = 1.0 mg/dl (male and female)
Age: 10 to < 13 years; Maximum Serum Creatinine (mg/dL): = 1.2 mg/dl (male and female)
13 to < 16 years; Maximum Serum Creatinine (mg/dL): = 1.5 mg/dl (male) and 1.4 mg/dl (female)
Age: >= 16 years; Maximum Serum Creatinine (mg/dL): = 1.7 mg/dl (male) and 1.4 mg/dl (female)
OR- a 24 hour urine creatinine clearance >= 50 mL/min/1.73 m^2
OR- a glomerular filtration rate (GFR) >= 50 mL/min/1.73 m^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)
Alanine aminotransferase (ALT) =< 3 x ULN for age (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)
Serum albumin >= 2 g/dl must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)
For patients with liver disease caused by their histiocytic disorder (as evaluated on radiographic imaging or biopsy): patients may be enrolled with abnormal bilirubin, aspartate aminotransferase (AST), ALT and albumin with documentation of histiocytic liver disease
Fractional shortening (FS) of >= 25% or ejection fraction of >= 50%, as determined by echocardiography or multigated acquisition scan (MUGA) within 28 days prior to study enrollment. Depending on institutional standard, either FS or left ventricular ejection fraction (LVEF) is adequate for enrollment if only one value is measured; if both values are measured, then both values must meet criteria above (must be obtained within 28 days prior to enrollment and start of protocol therapy) (repeat if necessary)
No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% if there is clinical indication for determination; unless it is due to underlying pulmonary LCH
Central Nervous System Function Defined As:
Patients with seizure disorder may be enrolled if well controlled
Central nervous system (CNS) toxicity =< Grade 2
Human immunodeficiency virus (HIV) infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial unless antiretroviral therapy interacts with the metabolism of tovorafenib (DAY101) and cannot safely be changed to antivirals that do not interact with study medication
Exclusion Criteria:
Principal Investigator: Ziad Khatib
Learn more at https://clinicaltrials.gov/study/NCT05828069.
A Single Arm, Open-Label, Phase 1b Trial of Epcoritamab in Pediatric Patients with Relapsed/ Refractory Aggressive Mature B-cell Neoplasms
Conditions: B-Cell Neioplasms
Eligibility: Participants >= 1 and < 18 years old at time of primary diagnosis with Burkitt's or Burkitt-like lymphoma/leukemia, diffuse large B-cell lymphoma (DLBCL), or other aggressive mature (CD20+) B-cell lymphomas. Participants up to 25 years of age with Burkitt's or Burkitt-like lymphoma/leukemia are also eligible.
Disease pathologically confirmed (tumor tissue) by local testing.
Relapsed or primary refractory disease meeting any of the following criteria:
Progressive disease at any time during second-line chemoimmunotherapy (CIT).
Best response of stable disease (SD) after a minimum of 2 cycles of second-line CIT.
Best response of partial response (PR) after a minimum of 3 cycles of second-line CIT.
Complete Response (CR) after a minimum of 3 cycles of second-line CIT therapy but unfit or ineligible for consolidation with cell therapy.
Not in CR and unable to initiate or tolerate (i.e., must discontinue) second-line CIT.
Have received cell therapy (allogeneic or autologous transplant or chimeric antigen receptor T-cell (CAR-T) therapy) as consolidation but have not obtained or maintained a CR.
Recovery from toxic effects of prior chemoimmunotherapy.
Performance status by Lansky (< 16 years old at evaluation) or Karnofsky (>= 16 years old at evaluation) score >= 50 or Eastern Cooperative Oncology Group (ECOG) score <= 2 .
Adequate bone marrow, hepatic, and renal function.
Principal Investigator: Maggie Fader
Learn more at https://clinicaltrials.gov/study/NCT05206357.
Newly Diagnosed Children (<10 y/o) With Medulloblastoma and Other CNS Embryonal Tumors: Clinical and Molecular Risk-Tailored Intensive and Compressed Induction Chemotherapy Followed by Consolidation With Either Single Cycle (Low-Risk Patients) Or Randomization (High Risk Patients) To Either Single-Cycle Or To Three Tandem Cycles Of Marrow-Ablative Chemotherapy With Autologous Hematopoietic Progenitor Cell Rescue
Conditions: Medulloblastoma
Principal Investigator: Ziad Khatib
Learn more at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237968/.
A Two-staged, Phase 2/3, Randomized, Multicenter Study to Evaluate the Efficacy and Safety of REC-2282 in Participants With Progressive NF2 Mutated Meningiomas
Conditions: Meningioma
Eligibility: 12 years of age and weighing at least 40 kg
Progressive meningioma that is amenable to volumetric analysis
Has either 1) sporadic meningioma with confirmed NF2 mutation; or, 2) confirmed diagnosis of NF2 disease (revised Manchester criteria); or, 3) at least one NF2-related tumor (with pathogenic germline or proven mosaic NF2 variant)
Adequate bone marrow function
Has provided written informed consent/assent to participate in the study
Exclusion Criteria
Progressive disease associated with significant or disabling clinical symptoms likely to require surgery or radiation therapy within the next 3 months.
Received prior surgery, radiosurgery, or laser interstitial thermal therapy in the target tumor, or immediately adjacent to the target tumor within 6 months prior to screening.
Received an anti- tumor agent for meningioma within 3 months, or 5 half-lives (whichever is longer), prior to screening.
History of an active malignancy within the previous 3 years except for localized cancers that are considered cured, and, in the opinion of the investigator, present a low risk of recurrence.
Received another investigational drug within 30 days prior to screening
Pregnant, lactating, or is planning to attempt to become pregnant or impregnate someone during this study or within 90 days after the last dose of IMP.
Principal Investigator: Ziad Khatib
CRA: Michelin Janvier
Learn more at https://clinicaltrials.gov/study/NCT05130866.
A Study Using Molecular Guided Therapy with Induction Chemotherapy followed by a Randomized Controlled Trial of standard immunotherapy with or without DFMO followed by DFMO maintenance for Subjects with Newly Diagnosed High-Risk Neuroblastoma
Conditions: Neuroblastoma
Eligibility: All patients must have a pathologically confirmed diagnosis of neuroblastoma, be age ≤ 21 years at initial diagnosis, and classified as high risk by the criteria used by COG or SIOPEN at the time of diagnosis. Exception: patients who are initially diagnosed as non-high-risk neuroblastoma, but later converted (and/or relapsed) to high risk neuroblastoma are also eligible.
Previous Therapy- subjects must fit into one of the strata categories listed in section 10.5 to be eligible to enroll on Part B of this study.
Pre-enrollment tumor survey:
Prior to enrollment on Part B, a determination of mandatory disease staging must be performed. Tumor imaging studies including CT or MRI, MIBG or PET, and VMA/HVA (PET scan should be done for patients with prior disease that was MIBG non-avid). Bone marrow aspirates and biopsies are required.
This disease assessment is required for eligibility and should be done preferably within 2 weeks, but must be done within a maximum of 4 weeks before first dose of study drug.
Timing- Enrollment to occur prior to Day + 120 post-transplant, preferably when the subject is within 28 days after completing local radiation therapy (if given).
Principal Investigator: Guillermo De Angulo
Learn more at https://clinicaltrials.gov/study/NCT02559778.
OKlahoma Nitrone-007: novel treatment for diffuse intrinsic pontine glioma
Conditions: Diffuse Midline Glioma
Principal Investigator: Ossama Maher
Learn more at https://clinicaltrials.gov/study/NCT05518838.
NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) - Phase 2 Subprotocol of LOXO-101 (Larotrectinib) in Patients With Tumors Harboring Actionable NTRK Fusions
Conditions: Solid tumors, non-Hodgkin lymphoma, or histiocytic disorders
Principal Investigator: Ziad Khatib
Learn more at https://clinicaltrials.gov/study/NCT03213704.
NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice)- Phase 2 Subprotocol of Ensartinib in Patients With Tumors Harboring ALK or ROS1 Genomic Alterations
Conditions: Solid tumors, non-Hodgkin lymphoma, or histiocytic disorders
Principal Investigator: Maggie Fader
Learn more at https://clinicaltrials.gov/study/NCT03213652.
NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) - Phase 2 Subprotocol of AG-120 (Ivosidenib) in Patients With Tumors Harboring IDH1 Mutations
Conditions: Solid tumors
Principal Investigator: Ziad Khatib
Learn more at https://clinicaltrials.gov/study/NCT04195555.
NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice)- Phase 2 Subprotocol of Tipifarnib in Patients With Tumors Harboring HRAS Genomic Alterations
Conditions: Tumor with Genomic Alterations
Principal Investigator: Ziad Khatib
Learn more at https://clinicaltrials.gov/study/NCT04284774.
NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) - Phase 2 Subprotocol of LOXO-292 in Patients With Tumors Harboring RET Gene Alterations
Conditions: Solid tumors
Principal Investigator: Ziad Khatib
Learn more at https://clinicaltrials.gov/study/NCT04320888.
Key Adverse Events after Childhood Cancer
Principal Investigator: Maggie Fader
Learn more at https://www.clinicaltrials.gov/study/NCT00082745.
Treatment of Newly Diagnosed Diffuse Anaplastic Wilms Tumors (DAWT) and Relapsed Favorable Histology Wilms Tumors (FHWT)
Conditions: Wilms Tumor
Eligibility: Patients with newly diagnosed stages 2 - 4 diffuse anaplastic Wilms tumor must be enrolled on AREN03B2 and have received an initial risk assignment showing DAWT (if anaplasia first identified at diagnostic, pre-treatment nephrectomy or biopsy) or a delayed nephrectomy classification showing DAWT (if anaplasia first noted at delayed nephrectomy) prior to enrollment on AREN1921. Prior enrollment on AREN03B2 is not an eligibility requirement for patients with relapsed favorable histology Wilms tumor.
Patients must be =< 30 years old at study enrollment
Patients with the following diagnoses are eligible for this study:
Newly diagnosed stages 2 - 4 diffuse anaplastic Wilms tumor as confirmed by central review
Favorable histology Wilms tumor at first relapse. Relapsed FHWT patients must have previously achieved remission for their initial FHWT diagnosis to be eligible for this study. The relapse risk groups are defined as follows, regardless of radiation therapy:
Standard-Risk relapse: Patients who received two chemotherapy agents for frontline therapy; primarily actinomycin D and vincristine
High-Risk relapse: Patients who received three chemotherapy agents for frontline therapy; primarily vincristine, actinomycin D and doxorubicin or vincristine, actinomycin D and irinotecan
Very High-Risk relapse: Patients who received four or more chemotherapy agents as part of initial therapy; primarily regimen M or its variations
Patients with newly diagnosed DAWT must have had histologic verification of the malignancy. For relapsed FHWT patients, biopsy to prove recurrence is encouraged, but not required
Note: For relapsed FHWT patients, an institutional pathology report confirming favorable histology Wilms tumor (from relapse, if available, or from original diagnosis) must be available for upload prior to initiation of protocol therapy
Patients with newly diagnosed Stages 2 - 4 diffuse anaplastic Wilms tumor must be enrolled on AREN1921 within 2 weeks of the tumor-directed surgery or biopsy procedure that first confirms a diagnosis of DAWT, whether at initial diagnostic procedure or delayed nephrectomy (such surgery/biopsy is day 0). For patients who received prior therapy for presumed favorable histology Wilms tumor, later confirmed to have diffuse anaplastic Wilms tumor at subsequent review of the initial biopsy
Patients with newly diagnosed DAWT who undergo upfront nephrectomy must have at least 1 lymph node sampled prior to study enrollment
Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
Patients must have a life expectancy of >= 8 weeks
Diffuse Anaplastic Wilms Tumor: Patients with diffuse anaplastic histology must have had no prior systemic therapy, except in the following situations:
Patients with diffuse anaplastic Wilms tumor who received no more than 12 weeks of pre nephrectomy chemotherapy for what was originally presumed to be favorable histology Wilms tumor, subsequently confirmed to be diffuse anaplastic Wilms tumor at delayed nephrectomy
Patients with diffuse anaplastic Wilms tumor who received no more than 6 weeks of chemotherapy following upfront biopsy, initiated within 14 days of biopsy, for presumed favorable histology Wilms tumor based on institutional review, but subsequently corrected to diffuse anaplastic Wilms tumor based on the AREN03B2 initial risk assignment results (if available per current version of AREN03B2)
Treatment consisting of vincristine/doxorubicin/cyclophosphamide initiated on an emergent basis and within allowed timing as described
Note: Patients who received prior therapy for presumed favorable histology Wilms tumor, later identified to have diffuse anaplastic Wilms tumor as per above, must begin study treatment starting at cycle 3 (week 7) of regimen UH 3. Patients who received emergency radiation to preserve organ function are eligible as noted. Patients who received radiation as part of standard of care for presumed newly diagnosed favorable histology Wilms tumor, along with chemotherapy as noted above, prior to identification of diffuse anaplasia, are also eligible
Relapsed Favorable Histology Wilms Tumor: Patients must not have received prior chemotherapy for their relapsed favorable histology Wilms tumor diagnosis. In addition, patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
Principal Investigator: Maggie Fader
Learn more at https://clinicaltrials.gov/study/NCT04322318.
Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
Conditions: Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders
Principal Investigator: Maggie Fader
CRA: Michelin Janvier
Learn more at https://www.clinicaltrials.gov/study/NCT03155620.
Thoracotomy Versus Thoracoscopic Management of Pulmonary Metastases in Patients With Osteosarcoma
Conditions: Sarcoma
Principal Investigator: Maggie Fader
Learn more at https://clinicaltrials.gov/study/NCT05235165.
Chemotherapy for the Treatment of Patients with Newly Diagnosed Very Low-Risk and Low Risk Fusion Negative Rhabdomyosarcoma
Conditions: Sarcoma
Oncology
Eligibility:
- Patients must be =< 21 years at the time of enrollment.
- Patients must have newly diagnosed embryonal rhabdomyosarcoma (ERMS), spindle cell/sclerosing RMS, or FOXO1 fusion negative alveolar rhabdomyosarcoma (ARMS) (institutional FOXO1 fusion results are acceptable). RMS types included under ERMS include those classified in the 1995 International Classification of Rhabdomyosarcoma (ICR) as ERMS (classic, spindle cell, and botryoid variants), which are reclassified in the 2020 World Health Organization (WHO) classification as ERMS (classic, dense and botryoid variants) and spindle cell/sclerosing RMS (encompassing the historical spindle cell ERMS variant and the newly recognized sclerosing RMS variant). Enrollment in APEC14B1 is required for all patients. * All patients will be evaluated for stage and clinical group. Note that clinical group designation assigned at the time of enrollment on study remains unchanged regardless of any second-look operation that may be performed. ** Patients will be eligible for the very low-risk stratum (Regimen VA) if they have Stage 1, CG I disease. ** Patients will be eligible for the low-risk stratum (Regimen VAC/VA) if they have Stage 1, CG II disease, Stage 2, CG I or II disease, or Stage 1, CG III (orbit only) disease. * Paratesticular Tumors: Staging ipsilateral retroperitoneal lymph node sampling (SIRLNS) is required for all patients >= 10 years of age with paratesticular tumors who do not have gross nodal involvement on imaging. * Extremity Tumors: Regional lymph node sampling is required for histologic evaluation in patients with extremity tumors. * Clinically or radiographically enlarged nodes must be sampled for histologic evaluation.
- Patients must have a Lansky (for patients =< 16 years of age) or Karnofsky (for patients > 16 years of age) performance status score of >= 50. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing performance score.
- Peripheral absolute neutrophil count (ANC) >= 750/uL (within 7 days prior to enrollment).
- Platelet count >= 75,000/uL (transfusion independent) (within 7 days prior to enrollment).
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine (within 7 days prior to enrollment) based on age/gender as follows: * Age: 1 month to < 6 months; Maximum serum creatinine (mg/dL): 0.4 (male) : 0.4 (female) * Age: 6 months to < 1 year; Maximum serum creatinine (mg/dL): 0.5 (male) : 0.5 (female) * Age: 1 to < 2 years; Maximum serum creatinine (mg/dL): 0.6 (male) : 0.6 (female) * Age: 2 to < 6 years; Maximum serum creatinine (mg/dL): 0.8 (male) : 0.8 (female) * Age: 6 to < 10 years; Maximum serum creatinine (mg/dL): 1 (male) : 1 (female) * Age: 10 to < 13 years; Maximum serum creatinine (mg/dL): 1.2 (male) : 1.2 (female) * Age: 13 to < 16 years; Maximum serum creatinine (mg/dL): 1.5 (male) : 1.4 (female) * Age >= 16 years; Maximum serum creatinine (mg/dL): 1.7 (male) : 1.4 (female)
- Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment), and * If there is evidence of biliary obstruction by the tumor, then the total bilirubin must be < 3 x ULN for age. * Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L.
- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L * If there is evidence of biliary obstruction by the tumor, then the total bilirubin must be < 3 x ULN for age * Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
- All patients and/or their parents or legal guardians must sign a written informed consent.
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.
Exclusion Criteria
- Patients who have received prior chemotherapy and/or radiation therapy for cancer prior to enrollment. Surgical resection alone of previous cancer(s) is permitted.
- Patients who have received chemotherapy or radiation for non-malignant conditions (e.g., autoimmune diseases) are eligible. Patients must discontinue chemotherapy for non-malignant conditions prior to starting protocol therapy.
- Vincristine is sensitive substrate of the CYP450 3A4 isozyme. Patients must not have received drugs that are moderate to strong CYP3A4 inhibitors and inducers within 7 days prior to study enrollment.
- Patients unable to undergo radiation therapy, if necessary, as specified in the protocol.
- Evidence of uncontrolled infection.
- Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
- Lactating females who plan to breastfeed their infants.
- Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation.
Principal Investigator: Maggie Fader
Learn more at
https://www.cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-01012&r=1.
NIH Ex-Vivo (FIU) Adopting a Functional Precision Medicine Approach to Reduce Cancer Disparities in Hispanic and Black Children of Miami
Conditions: Cancers
Principal Investigator: Maggie Fader
Learn more at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138443/.
Prospective Non-Interventional Study in Patients with Locally Advanced or Metastatic TRK Fusion Cancer Treated With Larotrectinib
Conditions: Tumors
Cancer
Principal Investigator: Ossama Maher
Learn more at https://clinicaltrials.gov/study/NCT04142437.
Managed Access Program (MAP) Cohort Treatment Plan CCTL019B2003I to provide access for patients with out of specification leukapheresis product and/or out of specification manufactured tisagenlecleucel (CTL019; Kymriah®)
Conditions: Leukemia
Oncology
Eligibility: Patient with B-cell acute lymphoblastic leukemia (ALL) or large B-cell lymphoma who were, per the treating physician assessment, eligible for treatment with tisagenlecleucel per the approved prescribing information (PI).
As per US PI, the approved indications are:
Patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse.
Adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high grade B-cell lymphoma and DLBCL arising from follicular lymphoma.
For other countries, please follow the locally approved PI or Summary of Product Characteristics (SmPC).
Has a patient specific batch of tisagenlecleucel allocated, however, either the incoming apheresis material is out of specification due to failure to meet acceptance specifications or the final manufactured product is out of specification due to failure to meet the commercial release specifications or other specification within the prescribing information. Attributes that may be out of specification:
Incoming leukapheresis: such as leukapheresis shelf life, T-cell percentage, absolute total nucleated cells, absolute T-cell count, and patient's viral testing including hepatitis B, hepatitis C, and HIV.
Final product: such as appearance (color), CAR identity, purity (T-cell percentage, cell viability, transduction efficiency by CAR quantitative PCR), impurities (residual beads, percentage of viable B-cells), quantity (for dose refer to Section 4), potency (CAR expression by flow cytometry and release of IFN? in response to CD19-expressing target cells), Safety: bacterial endotoxins, sterility, mycoplasma, VSV-G DNA)
Out of specification material has not been deemed to pose an undue safety risk to the patient
Is suffering from a serious or life-threatening disease or condition
Repeat leukapheresis is not clinically appropriate per the treating physician assessment
Does not have access to a comparable or satisfactory alternative treatment (i.e., comparable or satisfactory treatment is not available or does not exist)
Is not eligible for participation in any of the IMP's ongoing clinical trials or has recently completed a clinical trial that has been terminated and, after considering other options (e.g., trial extensions, amendments, etc.), the clinical team has determined that treatment is necessary and there are no other feasible alternatives for the patient
Principal Investigator: Guillermo De Angulo
Learn more at https://clinicaltrials.gov/study/NCT03601442.
Ex Vivo Drug Sensitivity Testing and Mutation Profiling
Conditions: Tumors
Principal Investigator: Maggie Fader
Learn more at https://classic.clinicaltrials.gov/ct2/show/NCT03860376.
A Randomized Phase 3 Interim Response Adapted Trial Comparing Standard Therapy with Immuno-oncology Therapy for Children and Adults with Newly Diagnosed Stage I and II Classic Hodgkin Lymphoma
Conditions: Hodgkin's Lymphoma
Eligibility: Patients must be 5 to 60 years of age at the time of enrollment.
3.2.2 Diagnosis
3.2.2.1 Patients with newly diagnosed untreated histologically confirmed classic Hodgkin lymphoma (cHL) (nodular sclerosis, mixed cellularity, lymphocyte-rich, or lymphocyte-depleted, or not otherwise specified (NOS)) with Stage I or II disease.
3.2.2.2 Patients must have bidimensionally measurable disease (at least one lesion with longest diameter ≥ 1.5 cm).
3.2.2.3 Patients must have a whole body or limited whole body PET scan performed within 42 days prior to enrollment. PET-CT is strongly preferred. PET-MRI allowed if intravenous contrast enhanced CT is also obtained.
3.2.2.4 Pediatric patients (age 5-17 years) must have an upright PA CXR for assessment of bulky mediastinal disease. Adult patients must have either a CXR or CT chest.
3.2.3 Performance Score
• Patients ≥ 18 years must have a performance status corresponding to Zubrod scores of 0, 1 or 2.
• Patients ≤ 17 years of age must have a Lansky performance score of ≥ 50.
See Appendix IV for details.
3.2.4 Organ Function Requirements
Please note that eligibility criteria and the timing of documentation prior to enrollment differ by age.
3.2.4.1 Adequate renal function defined as:
• For pediatric patients (age 5-17 years):
A serum creatinine* based on age/gender as follows: (See protocol)
OR - a 24 hour urine Creatinine clearance ≥ 50 mL/min/1.73 m2
OR - a GFR ≥ 50 mL/min/1.73 m2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard).
Note: Estimated GFR (eGFR) from serum or plasma creatinine, cystatin C or other estimates are not acceptable for determining eligibility.
• For adult patients (age 18 years or older):
Creatinine clearance ≥ 30 mL/min, as estimated by the Cockcroft and Gault formula or a 24-hour urine collection. The creatinine value used in the calculation must have been obtained within 28 days prior to registration. Estimated creatinine clearance is based on actual body weight.
Estimated creatinine clearance = (140 - age) x weight in kg †
72 x creatinine* (mg/dl)
Multiply this number by 0.85 if the participant is a female.
† The kilogram weight is the participant weight with an upper limit of 140% of the ideal body weight (IBW).
* Actual lab serum or plasma creatinine value with a minimum of 0.7 mg/dL.
3.2.4.2 Adequate liver function* defined as:
• Total bilirubin ≤ 2 x ULN, and
• AST and ALT ≤ 3 x ULN
Principal Investigator: Maggie Fader
Learn more at https://clinicaltrials.gov/study/NCT05675410.