SJiMB21: Phase 2 Study of Molecular and Clinical Risk-Directed Therapy for Infants and Young Children With Newly Diagnosed Medulloblastoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 130
- 试验地点
- 10
- 主要终点
- Progression free survival of G3/G4 infant (0-2.99 years) medulloblastoma patients treated with systemic chemotherapy and delayed risk-adapted CSI augmented with carboplatin.
研究概览
简要总结
This is a multi-center, multinational phase 2 trial that aims to explore the use of molecular and clinical risk-directed therapy in treatment of children 0-4.99 years of age with newly diagnosed medulloblastoma.
详细描述
The objectives of this study are:
Primary Objectives
- To estimate the progression free survival of SHH-2 infant (0-2.99 years) and young child (3-4.99 years) medulloblastoma patients treated with systemic HD-MTX- based chemotherapy only.
- To estimate the progression free survival of SHH-1 infant (0-2.99 years) medulloblastoma patients treated with systemic HD-MTX-based chemotherapy augmented with IVT-MTX.
- To estimate the progression free survival of G3/G4 infant (0-2.99 years) medulloblastoma patients treated with systemic chemotherapy and delayed risk- adapted CSI augmented with carboplatin.
- To compare cognitive outcomes among infants (0-2.99 years) and young children (3-4.99 years) treated with systemic chemotherapy only to patients treated with systemic chemotherapy and intra-ventricular chemotherapy or delayed risk- adapted craniospinal irradiation.
Secondary Objectives
- To investigate change in neurocognitive performance among infants (0-2.99 years) and young children (3-4.99 years) treated for medulloblastoma, and examine the impact of demographic factors (e.g., age at treatment, gender, and socioeconomic status), disease-related factors (e.g., presence of hydrocephalus, posterior fossa syndrome) and variants of proposed treatment regimen (e.g., systemic chemotherapy with or without IVT-MTX, radiation dosimetry to key brain structures, treatment-related ototoxicity) on cognitive late effects.
- To investigate which familial factors (e.g., family cohesion, family coping with medical management, parent-child interaction style) and environmental factors (e.g., parental verbal abilities, home literacy, adherence with rehabilitative therapies, participation in early intervention, school advocacy) associate with socioeconomic status and examine the impact of these factors on cognitive late effects.
- To evaluate the feasibility and acceptability of a caregiver education program paired with interactive neurodevelopmental games used to improve parent-child interactions, cognitive and social-emotional functioning in infants undergoing treatment for medulloblastoma. (funded by NCI via the R21CA280187)
- To estimate the magnitude of change in parent-child interactions following participation in a caregiver education paired with interactive neurodevelopmental games. (funded by NCI via the R21CA280187)
- To estimate the magnitude of change in cognition and social-emotional development associated with a caregiver education program combined with interactive neurodevelopmental games. (funded by NCI via the R21CA280187)
- To determine the extent of inter- and intra-patient variability in the plasma pharmacokinetics of high-dose systemic methotrexate, cyclophosphamide, vincristine, and topotecan in infants and young children with medulloblastoma, to assess potential covariates to explain this variability, and to explore associations between clinical effects and methotrexate, cyclophosphamide, vincristine, and topotecan pharmacokinetics.
- To determine the extent of inter- and intra-patient pharmacokinetic variability of methotrexate in ventricular CSF after intraventricular methotrexate dose administration in infants with medulloblastoma, and to explore associations between methotrexate CSF pharmacokinetics and clinical effects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 59 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Screening Phase (All Patients)
- •Participants with presumptive/suspected newly diagnosed medulloblastoma.
- •Participant meets one of the following criteria at the time of screening:
- •Age < 36 months OR Age ≥ 36 months and < 60 months with presumptive/suspected non-metastatic disease
- •Participant must have adequate tumor tissue from primary tumor for central review of pathology and molecular classification by methylation and IHC
- •Participant must be able to begin treatment as outlined in the protocol within 36 days of definitive surgery (day of surgery is Day 0). In case a second surgery is clinically indicated to remove the residual tumor prior to starting treatment, the second surgery will be considered as the definitive surgery (Day 0).
- •Parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines.
排除标准
- •Screening Phase
- •Participants with other clinically significant medical disorders (i.e., serious infections or significant cardiac, pulmonary, hepatic, psychiatric, or other organ dysfunction) that could compromise their ability to tolerate protocol therapy or would interfere with the study procedure.
- •Inclusion Criteria - Study Enrollment (All Patients)
- •Participant must be < 60 months of age at time of enrollment.
- •Note: Each treatment stratum has additional specific age requirements
- •Participant must have confirmation of newly diagnosed medulloblastoma per Central Review:
- •Central review includes histopathology, IHC and St. Jude Clinical Genomic Methylation Profiling conducted on MLPNet. If tissue or the extracted DNA does not meet quality control criteria for methylation analysis or if methylation classifier is unable assign molecular group/subgroup within the assigned classifier (MLPNet) parameters, then IHC will be used to define molecular group of these cases. IHC cannot be used to determine molecular subgroup. Therefore, IHC defined SHH patients will be enrolled on Stratum S-1 under "SHH-NOS", and all NWNS and indeterminate molecular group will be enrolled on stratum N.
- •Note: Diagnosis of medulloblastoma, as well as group and subgroup assignment, will be done by central pathology review at St. Jude only. No outside testing is allowed for trial enrollment.
- •Participant must have disease staged by MRI of the brain and spine and by cytologic examination of CSF* and be placed into the following categories:
- •M0: no evidence of metastatic disease.
- •must include a negative CSF cytology result
- •M1: Tumor cells found in the CSF but no other evidence of metastasis
- •M2: Intracranial tumor beyond the primary tumor site
- •M3: Metastatic disease in the spine
- •M4: Extraneural metastatic disease
- •*All participants are to undergo CSF cytologic examination regardless of presence or absence of gross metastatic disease unless procedure is medically contraindicated. CSF is to be obtained by lumbar puncture (LP) performed at least 10 days after surgery. If LP is medically contraindicated, ventricular CSF from a shunt or Ommaya reservoir may be used for staging but this is not the preferred option due to lower sensitivity. If LP is medically contraindicated and the patient doesn't have a shunt or reservoir for CSF sampling, the treating physician should reach out to PI or Co-PI regarding decision on enrollment to SJiMB
- •The decision to enroll without CSF cytology will be made on case-by-case basis.
- •Note: Participants who have M2 disease and positive CSF will be assigned to M
- •Note: Participants will be assigned to the highest stage number for which they meet eligibility.
- •Note: Treatment stratums may have additional stage requirements.
- •Patient must have received no previous radiotherapy, chemotherapy, or other brain tumor-directed therapy other than corticosteroid therapy and surgery.
- •Participant must have a Lansky performance score of > 30 (except for patients with posterior fossa syndrome.
- •Participant must have adequate organ function prior to study entry, as defined by:
- •Absolute neutrophil counts (ANC) >750/mm^3
- •Platelet count ≥ 50,000/mm^3 without support of a platelet transfusion within 7 days
- •Hemoglobin ≥8.0 g/dL (with or without support of a blood transfusion).
- •Normal liver function as defined by Alanine aminotransferase (ALT) concentration ≤ 3 x 45 U/L and total bilirubin ≤ 3 x 1.
- •Adequate renal function as defined by a serum creatinine concentration:
- •Age - 0 to <1year; Maximum Serum Creatinine (mg/dl) - Male 0.5; Female 0.5
- •Age - 1 to < 2years; Maximum Serum Creatinine (mg/dl) - Male 0.6; Female 0.6
- •Age - 1 to < 2yearsr; Maximum Serum Creatinine (mg/dl) - Male 0.8; Female 0.8
- •Participant's parent or legal guardian has the ability to understand and the willingness to sign a written informed consent document according to institutional guidelines.
- •Inclusion Criteria - Stratum S-2
- •Participant must have confirmed diagnosis of the following medulloblastoma molecular group and subgroup per Central Review.
- •Medulloblastoma SHH-2
- •Participant must meet one of the following criteria at time of enrollment:
- •Age <36 months OR Age ≥ 36 months and < 60 months with non-metastatic disease (M0) Inclusion Criteria - Stratum S-1
- •Participant must have confirmed diagnosis of one of the following medulloblastoma molecular subgroups per Central Review.
- •Medulloblastoma SHH-1
- •Medulloblastoma SHH-3
- •Medulloblastoma SHH-4
- •Medulloblastoma SHH-NOS
- •Includes medulloblastoma cases that could not be assigned to a molecular subgroup using the DNA methylation classifier, but which are in the SHH group and/or cases defined as SHH by IHC.
- •Participant must be < 36 months of age at time of enrollment
- •Note: Patients who are < 36 months of age, regardless of metastatic status (M0/M+), are eligible for enrollment on stratum S-
- •Inclusion Criteria - Stratum N
- •Participant must have confirmed diagnosis of one of the following medulloblastoma molecular subgroups per Central Review.
- •Medulloblastoma G3
- •Medulloblastoma G4
- •Medulloblastoma - Not classified into SHH (i.e., NWNS or indeterminate)
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研究组 & 干预措施
Stratum S-2
Patients with Sonic Hedgehog subgroup 2 (SHH-2), 0-2.99 years, or M0 and 3-4.99 years, will receive systemic high-dose methotrexate (HD-MTX) and conventional chemotherapy.
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Pegfilgrastim, Filgrastim
干预措施: Surgical resection (Procedure)
Stratum S-2
Patients with Sonic Hedgehog subgroup 2 (SHH-2), 0-2.99 years, or M0 and 3-4.99 years, will receive systemic high-dose methotrexate (HD-MTX) and conventional chemotherapy.
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Pegfilgrastim, Filgrastim
干预措施: Cisplatin (Drug)
Stratum S-2
Patients with Sonic Hedgehog subgroup 2 (SHH-2), 0-2.99 years, or M0 and 3-4.99 years, will receive systemic high-dose methotrexate (HD-MTX) and conventional chemotherapy.
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Pegfilgrastim, Filgrastim
干预措施: Vincristine (Drug)
Stratum S-2
Patients with Sonic Hedgehog subgroup 2 (SHH-2), 0-2.99 years, or M0 and 3-4.99 years, will receive systemic high-dose methotrexate (HD-MTX) and conventional chemotherapy.
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Pegfilgrastim, Filgrastim
干预措施: Carboplatin (Drug)
Stratum S-2
Patients with Sonic Hedgehog subgroup 2 (SHH-2), 0-2.99 years, or M0 and 3-4.99 years, will receive systemic high-dose methotrexate (HD-MTX) and conventional chemotherapy.
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Pegfilgrastim, Filgrastim
干预措施: Topotecan (Drug)
Stratum S-1
Patients with SHH-1, SHH-3, SHH-4, or SHH-Not otherwise specified (NOS), 0-2.99 years, will receive intraventricular methotrexate (IVT-MTX) in parallel with systemic HD-MTX and conventional chemotherapy.
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Pegfilgrastim, Filgrastim
干预措施: Methotrexate (Drug)
Stratum S-1
Patients with SHH-1, SHH-3, SHH-4, or SHH-Not otherwise specified (NOS), 0-2.99 years, will receive intraventricular methotrexate (IVT-MTX) in parallel with systemic HD-MTX and conventional chemotherapy.
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Pegfilgrastim, Filgrastim
干预措施: Cisplatin (Drug)
Stratum S-1
Patients with SHH-1, SHH-3, SHH-4, or SHH-Not otherwise specified (NOS), 0-2.99 years, will receive intraventricular methotrexate (IVT-MTX) in parallel with systemic HD-MTX and conventional chemotherapy.
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Pegfilgrastim, Filgrastim
干预措施: Vincristine (Drug)
Stratum S-1
Patients with SHH-1, SHH-3, SHH-4, or SHH-Not otherwise specified (NOS), 0-2.99 years, will receive intraventricular methotrexate (IVT-MTX) in parallel with systemic HD-MTX and conventional chemotherapy.
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Pegfilgrastim, Filgrastim
干预措施: Topotecan (Drug)
Stratum S-1
Patients with SHH-1, SHH-3, SHH-4, or SHH-Not otherwise specified (NOS), 0-2.99 years, will receive intraventricular methotrexate (IVT-MTX) in parallel with systemic HD-MTX and conventional chemotherapy.
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Pegfilgrastim, Filgrastim
干预措施: Pegfilgrastim (Drug)
Stratum S-1
Patients with SHH-1, SHH-3, SHH-4, or SHH-Not otherwise specified (NOS), 0-2.99 years, will receive intraventricular methotrexate (IVT-MTX) in parallel with systemic HD-MTX and conventional chemotherapy.
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Pegfilgrastim, Filgrastim
干预措施: Filgrastim (Drug)
Stratum N
Patients with Medulloblastoma (MB) group 3 or group 4 (G3/G4) or MB [including Non-WNT non-SHH medulloblastoma (NWNS) NOS or otherwise indeterminate cases] (0-2.99 years) will receive systemic HD-MTX and conventional chemotherapy only for radiation delaying purposes. At 3 years of age, these patients will receive risk-stratified craniospinal irradiation (CSI).
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Etoposide, Pegfilgrastim, Filgrastim, Radiation
干预措施: Surgical resection (Procedure)
Stratum N
Patients with Medulloblastoma (MB) group 3 or group 4 (G3/G4) or MB [including Non-WNT non-SHH medulloblastoma (NWNS) NOS or otherwise indeterminate cases] (0-2.99 years) will receive systemic HD-MTX and conventional chemotherapy only for radiation delaying purposes. At 3 years of age, these patients will receive risk-stratified craniospinal irradiation (CSI).
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Etoposide, Pegfilgrastim, Filgrastim, Radiation
干预措施: Methotrexate (Drug)
Stratum N
Patients with Medulloblastoma (MB) group 3 or group 4 (G3/G4) or MB [including Non-WNT non-SHH medulloblastoma (NWNS) NOS or otherwise indeterminate cases] (0-2.99 years) will receive systemic HD-MTX and conventional chemotherapy only for radiation delaying purposes. At 3 years of age, these patients will receive risk-stratified craniospinal irradiation (CSI).
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Etoposide, Pegfilgrastim, Filgrastim, Radiation
干预措施: Cisplatin (Drug)
Stratum N
Patients with Medulloblastoma (MB) group 3 or group 4 (G3/G4) or MB [including Non-WNT non-SHH medulloblastoma (NWNS) NOS or otherwise indeterminate cases] (0-2.99 years) will receive systemic HD-MTX and conventional chemotherapy only for radiation delaying purposes. At 3 years of age, these patients will receive risk-stratified craniospinal irradiation (CSI).
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Etoposide, Pegfilgrastim, Filgrastim, Radiation
干预措施: Cyclophosphamide (Drug)
Stratum N
Patients with Medulloblastoma (MB) group 3 or group 4 (G3/G4) or MB [including Non-WNT non-SHH medulloblastoma (NWNS) NOS or otherwise indeterminate cases] (0-2.99 years) will receive systemic HD-MTX and conventional chemotherapy only for radiation delaying purposes. At 3 years of age, these patients will receive risk-stratified craniospinal irradiation (CSI).
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Etoposide, Pegfilgrastim, Filgrastim, Radiation
干预措施: Carboplatin (Drug)
Stratum N
Patients with Medulloblastoma (MB) group 3 or group 4 (G3/G4) or MB [including Non-WNT non-SHH medulloblastoma (NWNS) NOS or otherwise indeterminate cases] (0-2.99 years) will receive systemic HD-MTX and conventional chemotherapy only for radiation delaying purposes. At 3 years of age, these patients will receive risk-stratified craniospinal irradiation (CSI).
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Etoposide, Pegfilgrastim, Filgrastim, Radiation
干预措施: Etoposide (Drug)
Stratum N
Patients with Medulloblastoma (MB) group 3 or group 4 (G3/G4) or MB [including Non-WNT non-SHH medulloblastoma (NWNS) NOS or otherwise indeterminate cases] (0-2.99 years) will receive systemic HD-MTX and conventional chemotherapy only for radiation delaying purposes. At 3 years of age, these patients will receive risk-stratified craniospinal irradiation (CSI).
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Etoposide, Pegfilgrastim, Filgrastim, Radiation
干预措施: Topotecan (Drug)
Stratum N
Patients with Medulloblastoma (MB) group 3 or group 4 (G3/G4) or MB [including Non-WNT non-SHH medulloblastoma (NWNS) NOS or otherwise indeterminate cases] (0-2.99 years) will receive systemic HD-MTX and conventional chemotherapy only for radiation delaying purposes. At 3 years of age, these patients will receive risk-stratified craniospinal irradiation (CSI).
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Etoposide, Pegfilgrastim, Filgrastim, Radiation
干预措施: Pegfilgrastim (Drug)
Stratum N
Patients with Medulloblastoma (MB) group 3 or group 4 (G3/G4) or MB [including Non-WNT non-SHH medulloblastoma (NWNS) NOS or otherwise indeterminate cases] (0-2.99 years) will receive systemic HD-MTX and conventional chemotherapy only for radiation delaying purposes. At 3 years of age, these patients will receive risk-stratified craniospinal irradiation (CSI).
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Etoposide, Pegfilgrastim, Filgrastim, Radiation
干预措施: Irradiation (Radiation)
Cognitive Study Group I (educational video and games)
Educational video and games
干预措施: Educational and Media Intervention (Other)
Stratum S-2
Patients with Sonic Hedgehog subgroup 2 (SHH-2), 0-2.99 years, or M0 and 3-4.99 years, will receive systemic high-dose methotrexate (HD-MTX) and conventional chemotherapy.
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Pegfilgrastim, Filgrastim
干预措施: Methotrexate (Drug)
Stratum S-2
Patients with Sonic Hedgehog subgroup 2 (SHH-2), 0-2.99 years, or M0 and 3-4.99 years, will receive systemic high-dose methotrexate (HD-MTX) and conventional chemotherapy.
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Pegfilgrastim, Filgrastim
干预措施: Filgrastim (Drug)
Stratum S-1
Patients with SHH-1, SHH-3, SHH-4, or SHH-Not otherwise specified (NOS), 0-2.99 years, will receive intraventricular methotrexate (IVT-MTX) in parallel with systemic HD-MTX and conventional chemotherapy.
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Pegfilgrastim, Filgrastim
干预措施: Cyclophosphamide (Drug)
Stratum S-1
Patients with SHH-1, SHH-3, SHH-4, or SHH-Not otherwise specified (NOS), 0-2.99 years, will receive intraventricular methotrexate (IVT-MTX) in parallel with systemic HD-MTX and conventional chemotherapy.
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Pegfilgrastim, Filgrastim
干预措施: Ommaya/VPS (Procedure)
Stratum S-1
Patients with SHH-1, SHH-3, SHH-4, or SHH-Not otherwise specified (NOS), 0-2.99 years, will receive intraventricular methotrexate (IVT-MTX) in parallel with systemic HD-MTX and conventional chemotherapy.
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Pegfilgrastim, Filgrastim
干预措施: Surgical resection (Procedure)
Stratum S-2
Patients with Sonic Hedgehog subgroup 2 (SHH-2), 0-2.99 years, or M0 and 3-4.99 years, will receive systemic high-dose methotrexate (HD-MTX) and conventional chemotherapy.
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Pegfilgrastim, Filgrastim
干预措施: Cyclophosphamide (Drug)
Cognitive Study Group II (standard-of-care control)
Standard-of-care (SOC) followed by educational video and games
干预措施: SOC, Educational and Media Intervention (Other)
Stratum S-2
Patients with Sonic Hedgehog subgroup 2 (SHH-2), 0-2.99 years, or M0 and 3-4.99 years, will receive systemic high-dose methotrexate (HD-MTX) and conventional chemotherapy.
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Pegfilgrastim, Filgrastim
干预措施: Pegfilgrastim (Drug)
Stratum S-1
Patients with SHH-1, SHH-3, SHH-4, or SHH-Not otherwise specified (NOS), 0-2.99 years, will receive intraventricular methotrexate (IVT-MTX) in parallel with systemic HD-MTX and conventional chemotherapy.
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Pegfilgrastim, Filgrastim
干预措施: Carboplatin (Drug)
Stratum N
Patients with Medulloblastoma (MB) group 3 or group 4 (G3/G4) or MB [including Non-WNT non-SHH medulloblastoma (NWNS) NOS or otherwise indeterminate cases] (0-2.99 years) will receive systemic HD-MTX and conventional chemotherapy only for radiation delaying purposes. At 3 years of age, these patients will receive risk-stratified craniospinal irradiation (CSI).
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Etoposide, Pegfilgrastim, Filgrastim, Radiation
干预措施: Vincristine (Drug)
Stratum N
Patients with Medulloblastoma (MB) group 3 or group 4 (G3/G4) or MB [including Non-WNT non-SHH medulloblastoma (NWNS) NOS or otherwise indeterminate cases] (0-2.99 years) will receive systemic HD-MTX and conventional chemotherapy only for radiation delaying purposes. At 3 years of age, these patients will receive risk-stratified craniospinal irradiation (CSI).
Interventions: Surgery, Methotrexate, Cisplatin, Vincristine, Cyclophosphamide, Carboplatin, Topotecan, Etoposide, Pegfilgrastim, Filgrastim, Radiation
干预措施: Filgrastim (Drug)
结局指标
主要结局
Progression free survival of G3/G4 infant (0-2.99 years) medulloblastoma patients treated with systemic chemotherapy and delayed risk-adapted CSI augmented with carboplatin.
时间窗: Up to 7 years after enrollment with PFS estimation occurring 2 years after treatment initiation of last patient
Progression free survival (PFS) will be measured from treatment initiation to the earliest of disease progression or death from any cause in stratum S-N eligible patients who receive at least 1 dose of the chemotherapy regimen. Patients who have not experienced one of these events will be censored at their last date of contact. The Kaplan-Meier estimate of PFS at two years will be computed. PFS will be compared to St. Jude historical cohorts using hazard ratios with 95% confidence intervals.
Executive function among infants and young children treated with systemic chemotherapy only compared to patients treated with systemic chemotherapy and intra-ventricular chemotherapy or delayed risk-adapted craniospinal irradiation
时间窗: Baseline through 5 years after enrollment
Change from baseline over time in executive functions will be assessed using different instruments as age appropriate. The Behavior Rating Inventory of Executive Function \[BRIEF-P (ages 2-5:11) and BRIEF-2 (ages 6-18)\] will assess behavioral manifestations of executive function. Longitudinal analyses will be conducted using mixed models.
Progression free survival of SHH-1 infant (0-2.99 years) medulloblastoma patients treated with systemic HD-MTX-based chemotherapy augmented with IVT-MTX.
时间窗: Up to 7 years after enrollment with PFS estimation occurring 2 years after treatment initiation of last patient
Progression free survival (PFS) will be measured from treatment initiation to the earliest of disease progression or death from any cause in stratum S-1 eligible SHH-1 patients who receive at least 1 dose of the chemotherapy regimen. Patients who have not experienced one of these events will be censored at their last date of contact. The Kaplan-Meier estimate of PFS at two years will be computed. PFS will be compared to St. Jude historical cohorts using hazard ratios with 95% confidence intervals.
IQ among infants and young children treated with systemic chemotherapy only compared to patients treated with systemic chemotherapy and intra-ventricular chemotherapy or delayed risk-adapted craniospinal irradiation
时间窗: Baseline through 5 years after enrollment
Change from baseline over time in intellectual function (IQ) will be assessed using different instruments as age appropriate. IQ will be measured in children 0-3:6 years of age using Bayley Scales of Infant and Toddler Development, Fourth Edition (Bayley-4), in children 3.0-5.11 years of age using Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV), and in children 6-10 years of age using Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V). Longitudinal analyses will be conducted using mixed models.
Health-related quality of life among infants and young children treated with systemic chemotherapy only compared to patients treated with systemic chemotherapy and intra-ventricular chemotherapy or delayed risk-adapted craniospinal irradiation
时间窗: Baseline through 5 years after enrollment
Changes from baseline over time in health-related quality of life will be assessed using the PedsQL (ages 2 and older). Longitudinal analyses will be conducted using mixed models.
Progression free survival of SHH-2 infant (0-2.99 years) and young child (3-4.99 years) medulloblastoma patients treated with systemic HD-MTX-based chemotherapy only.
时间窗: Up to 7 years after enrollment with PFS estimation occurring 2 years after treatment initiation of last patient
Progression free survival (PFS) will be measured from treatment initiation to the earliest of disease progression or death from any cause in stratum S-2 eligible M0 patients who receive at least 1 dose of the chemotherapy regimen. Patients who have not experienced one of these events will be censored at their last date of contact. The Kaplan-Meier estimate of PFS at two years will be computed. PFS will be compared to St. Jude historical cohorts using hazard ratios with 95% confidence intervals.
次要结局
- Change in executive function among infants (0-2.99 years) and young children (3-4.99 years) treated for medulloblastoma(Baseline through 5 years after enrollment)
- Evaluate intervention feasibility by measuring the rate of participants completing a caregiver education combined with interactive. neurodevelopmental games.(Baseline through 6 months after enrollment)
- Change in health-related quality of life among infants (0-2.99 years) and young children (3-4.99 years) treated for medulloblastoma(Baseline through 5 years after enrollment)
- Association of familial factors and environmental factors with socioeconomic status(Baseline through 5 years after enrollment)
- Association of familial factors and environmental factors with cognitive late effects.(Baseline through 5 years after enrollment)
- Evaluate family interest in caregiver education combined with interactive neurodevelopmental games.(Baseline through 6 months after enrollment)
- To assess potential covariates (e.g., demographics, clinical chemistry) explaining inter- and intra-patient variability in in the plasma systemic clearance (CL) of CTX in infants and young children with medulloblastoma receiving CTX.(Data for CTX from Day 9 of the first course of A, AIVT, B or BIVT therapy and Days 4 and 5 of course C or Days 2 and 3 of E.)
- To characterize the area under the concentration-time curve (AUC0-24h) of carboxyethylphosphoramide (CEPM) in infants and young children with medulloblastoma receiving cyclophosphamide.(Day 9 of the first course of A, AIVT, B or BIVT therapy and Days 4 and 5 of course C or Days 2 and 3 of E.)
- To characterize the plasma systemic methotrexate (MTX) clearance (CL) in infants and young children with medulloblastoma.(Day 1 of each course A, AIVT, B, and BIVT.)
- To assess potential covariates (e.g., demographics, clinical chemistry) explaining inter- and intra-patient variability in MTX PK parameter CL in infants and young children with medulloblastoma receiving MTX.(Day 1 of each course A, AIVT, B, and BIVT.)
- To assess potential covariates (e.g., demographics, clinical chemistry) explaining inter- and intra-patient variability in 7OHMTX PK parameter AUC0-24h in infants and young children with medulloblastoma receiving MTX.(Day 1 of each course A, AIVT, B, and BIVT.)
- Change in IQ among infants (0-2.99 years) and young children (3-4.99 years) treated for medulloblastoma(Baseline through 5 years after enrollment)
- Evaluate the acceptability of a caregiver education combined with interactive neurodevelopmental games.(Baseline through 6 months after enrollment)
- Magnitude of change in cognition and social-emotional development associated with a caregiver education program combined with interactive neurodevelopmental games.(Baseline and 6 months after enrollment)
- To characterize the plasma systemic clearance (CL) of cyclophosphamide (CTX) in infants and young children with medulloblastoma.(Day 9 of the first course of A, AIVT, B or BIVT therapy and Days 4 and 5 of course C or Days 2 and 3 of E.)
- To characterize the area under the concentration-time curve (AUC0-24h) of 4-hydroxy-cyclophosphamide (4OHCTX) in infants and young children with medulloblastoma receiving cyclophosphamide.(Day 9 of the first course of A, AIVT, B or BIVT therapy and Days 4 and 5 of course C or Days 2 and 3 of E.)
- To characterize the plasma systemic clearance (CL) of topotecan (TPT) in infants and young children with medulloblastoma.(All samples acquired during each course C for domestic patients and patients at St. Jude only.)
- To assess potential covariates (e.g., demographics, clinical chemistry) explaining inter- and intra-patient variability in TPT PK parameter (CL) in infants and young children with medulloblastoma receiving TPT.(All samples acquired during each course C for domestic patients and patients at St. Jude, only.)
- To assess potential covariates (e.g., demographics, clinical chemistry) explaining inter- and intra-patient variability in CEPM AUC0-24h in infants and young children with medulloblastoma receiving CTX.(Data for CEPM from Day 9 of the first course of A, AIVT, B or BIVT therapy and Days 4 and 5 of course C or Days 2 and 3 of E.)
- To assess potential covariates (e.g., demographics, clinical chemistry) explaining inter- and intra-patient variability in 4OHCTX AUC0-24h in infants and young children with medulloblastoma receiving CTX.(Data for 4OHCTX from Day 9 of the first course of A, AIVT, B or BIVT therapy and Days 4 and 5 of course C or Days 2 and 3 of E.)
- To characterize the area under the concentration-time curve (AUC0-24h) of 7-hydroxymethotrexate (7OHMTX) in infants and young children with medulloblastoma receiving methotrexate.(Day 1 of each course A, AIVT, B, and BIVT.)
- To characterize the plasma systemic clearance (CL) of vincristine (VCR) in infants and young children with medulloblastoma.(Beginning on Day 15 of the first course of A or AIVT and B or BIVT (or Day 8 of one course E).)
- To assess potential covariates (e.g., demographics, clinical chemistry) explaining inter- and intra-patient variability in VCR PK parameter (CL) in infants and young children with medulloblastoma receiving VCR.(Beginning on Day 15 of the first course of A or AIVT and B or BIVT (or Day 8 of one course E).)