Combination Chemotherapy Followed by Bone Marrow and/or Peripheral Stem Cell Transplantation in Treating Patients With Recurrent Medulloblastoma or CNS Germ Cell Tumors

Children's Oncology Group

Status and phase: Completed; Phase 2

Conditions: Brain Tumor; Central Nervous System Tumor

Treatments: Procedure: autologous bone marrow transplantation; Drug: melphalan; Drug: cyclophosphamide; Procedure: bone marrow ablation with stem cell support; Biological: Sargramostim; Procedure: peripheral blood stem cell transplantation

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00002594

CDR0000063784 (Other Identifier)

COG-P9430 (Other Identifier)

POG-9430 (Other Identifier)

9430

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so that they stop growing or die. bone marrow transplantation and peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by bone marrow transplantation and/or peripheral stem cell transplantation in treating patients who have recurrent medulloblastoma or CNS germ cell tumors.

Full description

OBJECTIVES:

• Determine the response and progression-free survival in patients with recurrent medulloblastoma or CNS germ cell tumors treated with intensive melphalan and cyclophosphamide followed by autologous bone marrow and/or peripheral blood stem cell rescue.
• Determine the acute and delayed toxic effects of this regimen in these patients.

OUTLINE: Autologous bone marrow and/or peripheral blood stem cells (PBSC) are harvested. Patients then receive intensive cyclophosphamide IV over 1 hour on days -8 to -5 and melphalan IV over 15 minutes on days -4 to -2. Bone marrow is reinfused on day 0. PBSC are reinfused on day 0 if used alone or on day 1 if used after autologous bone marrow transplantation (ABMT). Sargramostim (GM-CSF) is administered IV over 2 hours daily beginning 4 hours after ABMT and continuing until blood counts recover.

Patients are followed every 6 months through year 4 and then annually thereafter.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 2.5 years.

Enrollment: 31 patients

Sex: All

Ages: 2 to 25 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Diagnosis of recurrent medulloblastoma or CNS germ cell tumor

  • Histologic review of the primary intracranial or spinal cord tumor required

    • Biopsy and reduction of tumor bulk prior to study encouraged but not required

• No more than 1 prior primary therapy (radiotherapy or chemoradiotherapy) and/or 1 prior salvage therapy

  • Patients with progression on salvage therapy ineligible

• Minimal residual disease (tumor bulk no more than 1.5 cm) or in second clinical complete remission (CR)

• Bone marrow infiltration with or without mass lesions or isolated abnormal CSF cytology as the only manifestation of recurrent disease allowed if a clinical CR is first achieved with conventional therapy

PATIENT CHARACTERISTICS:

Age:

• 2 to 25

Performance status:

• Karnofsky 80-100%

Life expectancy:

• More than 8 weeks

Hematopoietic:

• Absolute neutrophil count greater than 1,000/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic:

• Bilirubin less than 1.5 mg/dL
• SGPT less than 80 IU

Renal:

• Creatinine less than 1.2 mg/dL

Cardiovascular:

• LVEF normal

Other:

• No infection
• Able to tolerate vigorous hydration
• Not pregnant
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• Prior cyclophosphamide or ifosfamide allowed

Endocrine therapy:

• No concurrent dexamethasone as an antiemetic
• Other concurrent corticosteroids allowed

Radiotherapy:

• See Disease Characteristics
• Pretransplantation radiotherapy boost allowed

Surgery:

• See Disease Characteristics
• Pretransplantation surgery allowed

Other:

• At least 4 weeks since prior therapy except corticosteroids

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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31 participants in 1 patient group

Ablative chemo followed by autologous bone marrow (ABM) rescue

Experimental group

Description:

Autologous bone marrow and/or peripheral blood stem cells (PBSC) are harvested. Patients then receive intensive cyclophosphamide IV over 1 hour on days -8 to -5 and melphalan IV over 15 minutes on days -4 to -2. Bone marrow is reinfused on day 0. PBSC are reinfused on day 0 if used alone or on day 1 if used after autologous bone marrow transplantation (ABMT). Sargramostim (GM-CSF) is administered IV over 2 hours daily beginning 4 hours after ABMT and continuing until blood counts recover.

Treatment:

Biological: Sargramostim

Drug: cyclophosphamide

Procedure: autologous bone marrow transplantation

Drug: melphalan

Procedure: bone marrow ablation with stem cell support

Procedure: peripheral blood stem cell transplantation