RATIONALE: Gene therapy may improve the body's ability to fight cancer or make the cancer more sensitive to chemotherapy. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: This phase I trial is studying the side effects and best dose of gene therapy together with chemotherapy in treating patients with advanced solid tumors or non-Hodgkin's lymphoma.
Name: filgrastim
Description: Patients receive filgrastim (G-CSF) subcutaneously (SC) once daily on days 1-5 (or G-CSF twice daily alone for 4-5 days).Type: Biological
Name: sargramostim
Description: Patients receive sargramostim (GM-CSF) subcutaneously (SC) once daily on days 1-5 (or G-CSF twice daily alone for 4-5 days).Type: Biological
Name: therapeutic autologous lymphocytes
Type: Biological
Name: O6-benzylguanine
Description: Patients receive O6-benzylguanine (BG) IV over 1 hour every 6 weeks for 5 courses. Four weeks after the completion of BG and carmustine, patients receive BG IV over 1 hour every 4 weeks for up to 5 courses, in the absence of hematologic toxicity. Patients with responding disease may continue to receive BG and temzolomide in the absence of disease progression or unacceptable toxicity.Type: Drug
Name: carmustine
Description: Patients receive carmustine IV over 1 hour every 6 weeks for 5 courses.Cohorts of 3-6 patients receive escalating numbers of CD34 stem cells targeted for retroviral infection and escalating doses of carmustine.Type: Drug
Name: temozolomide
Description: Four weeks after the completion of BG and carmustine, patients receive temozolomide IV over 1 hour every 4 weeks for up to 5 courses, in the absence of hematologic toxicity. Patients with responding disease may continue to receive BG and temzolomide in the absence of disease progression or unacceptable toxicity.Type: Drug
Name: in vitro-treated peripheral blood stem cell transplantation
Description: Approximately 72 hours after the end of the first course of chemotherapy, patients receive reinfusion of retrovirally-transduced hematopoietic stem cells over 5-10 minutes. Cohorts of 3-6 patients receive escalating numbers of CD34 stem cells targeted for retroviral infection and escalating doses of carmustine.Type: ProcedureSingle Group Assignment
There is one SNP
DISEASE CHARACTERISTICS: - One of the following histologically confirmed diseases for which no curative surgical, radiotherapy, or chemotherapy programs are available and standard therapy offers, at best, a modest clinical benefit - Solid tumors - Gliomas - Non-Hodgkin's lymphoma - Primary and metastatic CNS malignancies are eligible - Evaluable or measurable disease - CD34 count at least 2.0 cells/μL - No bone marrow involvement - Histologically negative bone marrow biopsy PATIENT CHARACTERISTICS: Age: - 18 to 70 Performance status: - ECOG 0-2 Life expectancy: - At least 12 weeks Hematopoietic: - Absolute neutrophil count at least 1,500/mm^3 - Platelet count at least 100,000/mm^3 - Hemoglobin at least 8.5 g/dL Hepatic: - Bilirubin no greater than 1.5 mg/dL - AST and ALT less than 2.5 times normal - Prothrombin time less than 1.2 times normal Renal: - Creatinine no greater than 2.0 mg/dL Cardiovascular: - No acute cardiac disease by EKG Pulmonary: - No symptomatic pulmonary disease Other: - HIV negative - No other severe comorbid conditions - Not pregnant or nursing - Fertile patients must use effective contraception during and for 2 months after study completion PRIOR CONCURRENT THERAPY: Biologic therapy: - See Chemotherapy - No prior hematopoietic stem cell transplantation Chemotherapy: - No prior high-dose chemotherapy - Prior adjuvant chemotherapy allowed Endocrine therapy: - Not specified Radiotherapy: - No prior radiotherapy to 25% or more of bone marrow Surgery: - Not specified Other: - At least 4 weeks since prior myelosuppressive therapy DISEASE CHARACTERISTICS: - One of the following histologically confirmed diseases for which no curative surgical, radiotherapy, or chemotherapy programs are available and standard therapy offers, at best, a modest clinical benefit - Solid tumors - Gliomas - Non-Hodgkin's lymphoma - Primary and metastatic CNS malignancies are eligible - Evaluable or measurable disease - CD34 count at least 2.0 cells/μL - No bone marrow involvement - Histologically negative bone marrow biopsy PATIENT CHARACTERISTICS: Age: - 18 to 70 Performance status: - ECOG 0-2 Life expectancy: - At least 12 weeks Hematopoietic: - Absolute neutrophil count at least 1,500/mm^3 - Platelet count at least 100,000/mm^3 - Hemoglobin at least 8.5 g/dL Hepatic: - Bilirubin no greater than 1.5 mg/dL - AST and ALT less than 2.5 times normal - Prothrombin time less than 1.2 times normal Renal: - Creatinine no greater than 2.0 mg/dL Cardiovascular: - No acute cardiac disease by EKG Pulmonary: - No symptomatic pulmonary disease Other: - HIV negative - No other severe comorbid conditions - Not pregnant or nursing - Fertile patients must use effective contraception during and for 2 months after study completion PRIOR CONCURRENT THERAPY: Biologic therapy: - See Chemotherapy - No prior hematopoietic stem cell transplantation Chemotherapy: - No prior high-dose chemotherapy - Prior adjuvant chemotherapy allowed Endocrine therapy: - Not specified Radiotherapy: - No prior radiotherapy to 25% or more of bone marrow Surgery: - Not specified Other: - At least 4 weeks since prior myelosuppressive therapy Brain and Central Nervous System Tumors Lymphoma Unspecified Adult Solid Tumor, Protocol Specific Lymphoma Neoplasms Nervous System Neoplasms Central Nervous System Neoplasms OBJECTIVES: - Evaluate the feasibility of introducing and expressing mutant MGMT-G156A cDNA in hematopoietic progenitors taken from patients with advanced solid tumors (including gliomas) or non-Hodgkin's lymphoma using a safety modified retroviral vector MFG. - Determine the toxicity associated with reinfusion of ex vivo-transduced hematopoietic stem cells into these patients, including the detection of replication competent retrovirus. --- G156A ---
- Evaluate the feasibility of identifying mutant MGMT-G156A-transduced and O6-benzylguanine (BG)- and temzolomide-resistant hematopoietic and stromal progenitors from the bone marrow of these patients. --- G156A ---
The CD34 positive stem cells are then infected by the retroviral mutant MGMT-G156A ex vivo. --- G156A ---