RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Bone marrow or peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill tumor cells.

PURPOSE: Phase II trial to study the effectiveness of chemotherapy followed by autologous bone marrow or peripheral stem cell transplantation in treating patients with glioblastoma multiforme or brain stem tumors.

Condition	Treatment or Intervention	Phase
high-grade childhood cerebral astrocytoma adult glioblastoma multiforme adult brain stem glioma untreated childhood brain stem glioma	Drug: carboplatin  Drug: filgrastim  Drug: thiotepa	Phase II

Further Study Details: 

OBJECTIVES: I. Estimate the overall survival, progression-free interval, and time to progression or recurrence in patients with nondisseminated glioblastoma multiforme or diffuse intrinsic brain stem tumors that are nonprogressive following surgery (if feasible) and involved-field irradiation and treated with intensive chemotherapy followed by autologous peripheral blood stem cell (PBSC) or autologous bone marrow (ABM) rescue.

II. Estimate the toxicity of myeloablative chemotherapy with thiotepa (TSPA) followed by carboplatin (CBDCA) in these patients.

III. Evaluate the pharmacokinetic interactions of high-dose CBDCA, TSPA, and triethylenephosphoramide (a metabolite of TSPA) and any impact on subsequent toxicity.

IV. Evaluate the effectiveness of autologous stem cells in restoring hematopoiesis following myeloablative therapy.

PROTOCOL OUTLINE: All patients undergo bone marrow or stem cell harvest (investigator option) no later than 12 weeks after completion of radiotherapy. The following acronyms are used: ABM Autologous Bone Marrow CBDCA Carboplatin, NSC-241240 G-CSF Granulocyte Colony-Stimulating Factor (Amgen), NSC-614629 PBSC Peripheral Blood Stem Cells TSPA Thiotepa, NSC-6396

2-Drug Myeloablative Chemotherapy followed by Hematopoietic Rescue. TSPA; CBDCA; followed by ABM or PBSC; G-CSF.

PROJECTED ACCRUAL: 60 patients will be entered over 3 years. If more than 5 patients on any arm experience treatment-related mortality, accrual will be discontinued.

Ages Eligible for Study:  6 Years   -   59 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Glioblastoma multiforme (GBM) or brain stem tumor following surgery (if feasible) and local radiotherapy, as follows: Pathologically confirmed primary GBM; Gliosarcomas and multifocal GBM eligible; Unbiopsied diffuse intrinsic pontine tumors; Nonenhancing with gadolinium on MRI; T1 hypodense and T2 hyperdense
• No recurrent or progressing disease following radiotherapy
• No leptomeningeal dissemination by radiographic evaluation including head MRI and either whole-spine MRI with gadolinium or myelogram; Positive CSF cytology alone allowed
• No extraneural metastases

--Prior/Concurrent Therapy--

• Radical surgery and involved-field radiotherapy (at least 4,500 cGy) completed within 6 weeks prior to entry; Second surgical debulking following radiotherapy strongly encouraged for patients with residual tumor mass or suspected radionecrosis; Requirement for surgery waived for unresectable brainstem tumors
• No prior chemotherapy except corticosteroids

--Patient Characteristics--

• Age: 6 to under 60
• Performance status: Karnofsky 70%-100% (over age 16); Lansky 70%-100% (ages 6-16)
• Hematopoietic: Not specified
• Hepatic: Bilirubin less than 2.0 mg/dL; AST or ALT less than 5 times normal; PT and aPTT normal (consult with principal investigator if abnormal)
• Renal: Creatinine clearance at least 50 mL/min/1.73 sqm
• Cardiovascular: No evidence of myocardial infarction or ischemia on EKG
• Other: No active infection at time of leukapheresis; Able to tolerate anticoagulation

New York
      Kaplan Cancer Center, New York,  New York,  10016,  United States

Study chairs or principal investigators

Jonathan L. Finlay,  Study Chair,  Kaplan Cancer Center   

Study ID Numbers:  CDR0000063964; NYU-97-8; NCI-V94-0594; MSKCC-94101
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002619
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08