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

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.

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