Thiotepa Followed by Peripheral Stem Cell or Bone Marrow Transplant in Treating Patients With Malignant Glioma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Giving chemotherapy with peripheral stem cell or bone marrow transplant may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: This phase II trial is studying how well thiotepa followed by peripheral stem cell or bone marrow transplant works in treating patients with malignant glioma.

Detailed Description
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OBJECTIVES: Determine the response rate, disease-free interval, and overall survival of patients with malignant glioma treated with high-dose thiotepa followed by autologous peripheral blood stem cell transplantation. Determine the toxicity of this regimen in these patients. Determine the pharmacokinetics of this regimen in these patients. Determine whether this drug enters the cerebrospinal fluid of these patients. OUTLINE: Following a course of induction chemotherapy with cyclophosphamide IV over 4 hours, patients receive filgrastim (G-CSF) daily until the completion of peripheral blood stem cell (PBSC) harvesting. PBSCs are collected over 3-5 days. Patients who do not mobilize sufficient cells undergo bone marrow harvest. Patients receive high-dose thiotepa IV over 5 hours on day -2. PBSCs or bone marrow are reinfused on day 0. Patients receive sargramostim (GM-CSF) subcutaneously daily beginning on day 0 and continuing until blood counts recover. Treatment repeats every 2-3 weeks for a total of 1-4 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, at every course, then monthly for 6 months, and then every 2 months thereafter. Patients are followed monthly for 6 months and then every 2 months thereafter. PROJECTED ACCRUAL: A total of 5-40 patients will be accrued for this study within 3 years.

Official Title
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CAMP 013:- Tandem Thiotepa Regimen For Selected Malignant Gliomas:1) Primary Or Recurrent Glioblastoma Multiforme (GBM); and 2) Recurrent Anaplastic Astrocytomas (AA), Oligodendrogliomas (O), Oligoastrocytomas (OA), Ependymomas And Primitive Neuroectodermal Tumors (PNET) That Have Either Progressed After Primary Therapy Or Are Refractory To Standard Chemotherapy

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Biological: filgrastim
* Biological: sargramostim
* Drug: cyclophosphamide
* Drug: thiotepa
* Procedure: autologous bone marrow transplantation
* Procedure: bone marrow ablation with stem cell support
* Procedure: peripheral blood stem cell transplantation


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed malignant glioma Primary or recurrent glioblastoma multiforme (including gliosarcoma) following surgery and radiotherapy or prior conventional chemotherapy (e.g., carmustine or procarbazine, vincristine, and lomustine) Recurrent or refractory anaplastic astrocytoma following any prior therapy (must be chemoresistant) Recurrent or refractory ependymoma or primitive neuroectodermal tumor (PNET) following any prior therapy Recurrent or refractory oligodendroglioma or oligoastrocytoma following any prior therapy (must be chemoresistant) Evaluable disease on gadolinium-enhanced MRI Ineligible for other high priority national or institutional study (e.g., protocol CAMP-004) PATIENT CHARACTERISTICS: Age: Any age Performance status: ECOG 0-1 Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Creatinine less than 1.5 times normal Cardiovascular: LVEF at least 45% by MUGA Pulmonary: DLCO at least 60% of predicted OR Approval by pulmonologist Other: Not pregnant or nursing Fertile patients must use effective contraception HIV negative PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics No other concurrent chemotherapy Endocrine therapy: No concurrent anticancer hormonal therapy No concurrent steroids as antiemetics Radiotherapy: See Disease Characteristics See Surgery Surgery: See Disease Characteristics For patients with glioblastoma multiforme, concurrent surgery and/or stereotactic radiosurgery to reduce tumor bulk allowed Other: No concurrent acetaminophen during chemotherapy
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: filgrastim|nan|
|Biological: sargramostim|nan|
|Drug: cyclophosphamide|nan|
|Drug: thiotepa|nan|
|Procedure: autologous bone marrow transplantation|nan|
|Procedure: bone marrow ablation with stem cell support|nan|
|Procedure: peripheral blood stem cell transplantation|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate |  |  | 
| Disease-free interval |  |  | 
| Overall survival |  |  | 
| Toxicity |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics |  |  | 
| Presence of high-dose thiotepa in the cerebrospinal fluid |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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childhood infratentorial ependymoma, childhood supratentorial ependymoma, recurrent adult brain tumor, adult medulloblastoma, adult glioblastoma, adult oligodendroglioma, childhood high-grade cerebral astrocytoma, childhood oligodendroglioma, adult anaplastic astrocytoma, adult anaplastic ependymoma, adult mixed glioma, recurrent childhood supratentorial primitive neuroectodermal tumor, recurrent childhood cerebellar astrocytoma, recurrent childhood cerebral astrocytoma, recurrent childhood ependymoma, adult giant cell glioblastoma, adult gliosarcoma, adult supratentorial primitive neuroectodermal tumor (PNET)