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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00002594
First received: November 1, 1999
Last updated: July 23, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Brain Tumor
Central Nervous System Tumor
Biological: Sargramostim
Drug: cyclophosphamide
Drug: melphalan
Procedure: autologous bone marrow transplantation
Procedure: bone marrow ablation with stem cell support
Procedure: peripheral blood stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Dose-Intensive Melphalan and Cyclophosphamide With Autologous Bone Marrow Rescue for Recurrent Medulloblastoma and Germ Cell Tumors

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: 1-2 years ] [ Designated as safety issue: No ]

Enrollment: 31
Study Start Date: September 1994
Study Completion Date: March 2007
Primary Completion Date: September 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ablative chemo followed by autologous bone marrow (ABM) rescue
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.
Biological: Sargramostim
Given IV
Other Names:
  • M-CSF
  • GM-CSF
  • Granulocyte macrophage-colony stimulating factor
  • Prokine
  • Leukine
  • NSC #6137
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC #026271
  • IND #7089
Drug: melphalan
Given IV
Other Names:
  • ylalanine mustard
  • L-PAM
  • L-sarcolysin
  • Alkeran
  • NSC #8806
Procedure: autologous bone marrow transplantation Procedure: bone marrow ablation with stem cell support Procedure: peripheral blood stem cell transplantation

Detailed 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.

  Eligibility

Ages Eligible for Study:   2 Years to 25 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002594

  Show 118 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Donald H. Mahoney, MD Texas Children's Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00002594     History of Changes
Other Study ID Numbers: 9430, COG-P9430, POG-9430, CDR0000063784
Study First Received: November 1, 1999
Last Updated: July 23, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
recurrent childhood brain tumor
childhood central nervous system germ cell tumor
recurrent childhood medulloblastoma

Additional relevant MeSH terms:
Neoplasms
Brain Neoplasms
Nervous System Neoplasms
Central Nervous System Neoplasms
Medulloblastoma
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neuroectodermal Tumors, Primitive
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Cyclophosphamide
Melphalan
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on September 18, 2014