Title
Gene Therapy, Chemotherapy, and Peripheral Stem Cell Transplantation in Treating Patients With HIV-Related Non-Hodgkin's Lymphoma
A Phase I/II Study of the Safety and Feasibility of REVM10 or REVM10/ANTISENSE POL 1 Transduced Hematopoietic Stem Cells (HSC) in HIV-1 Related Non-Hodgkin's Lymphoma Patients Already Being Treated With High Dose Chemotherapy and Peripheral Blood Stem Cell Support
Phase
Phase 1/Phase 2Lead Sponsor
SystemixStudy Type
InterventionalStatus
Unknown statusIndication/Condition
LymphomaIntervention/Treatment
revm10 gene revm10/polas gene ...Study Participants
15RATIONALE: Inserting the gene for RevM10 into a person's peripheral stem cells may improve the body's ability to fight cancer or make the cancer more sensitive to chemotherapy.
PURPOSE: Phase I/II trial to study the effectiveness of RevM10-treated stem cells plus chemotherapy and peripheral stem cell transplantation in treating patients who have HIV-related non-Hodgkin's lymphoma.
OBJECTIVES: I. Determine the safety of infusion of RevM10 or RevM10/polAS transduced hematopoietic stem cells (HSC) in addition to high dose chemotherapy and standard peripheral blood stem cell support in patients with HIV-1 related non-Hodgkin's lymphoma. II. Determine gene marking of lymphocytes and myeloid cells in peripheral blood, bone marrow, and/or lymph nodes after infusion of RevM10-HSC or RevM10/polAS-HSC in these patients. III. Determine the antiretroviral effect of this treatment in these patients.
OUTLINE: This is a multicenter study. Patients receive mobilization therapy and undergo leukapheresis according to a standard protocol. High dose chemotherapy is administered on days -7 to -1, also according to a standard protocol. On day 0, autologous hematopoietic stem cells transduced with genes RevM10 or RevM10/polAS are infused. Unmodified autologous peripheral blood stem cells are reinfused on day 1. Patients are followed daily for 2 weeks, weekly for 2 weeks, monthly for 1 year, then annually thereafter.
PROJECTED ACCRUAL: Approximately 15 patients will be accrued for this study within 14 months.
DISEASE CHARACTERISTICS: HIV-1 infection documented by ELISA and Western blot Histologically proven non-Hodgkin's lymphoma showing at least partial response to standard chemotherapy regimen Poor prognosis in first chemotherapy induced remission Increased LDH AND/OR Stage III or IV AND/OR Reduced performance status (ECOG 2 or worse) OR Response but no complete remission following four courses of standard chemotherapy OR Responding relapse after primary therapy No primary CNS lymphoma No uncontrolled meningeal lymphoma at mobilization PATIENT CHARACTERISTICS: Age: 18 and over Performance status: See Disease Characteristics Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1500/mm3 Platelet count at least 100,000/mm3 CD4 count at least 100/mm3 Hepatic: Bilirubin less than 2 mg/dL (unless taking indinavir) SGOT and SGPT less than 2 times normal No hepatitis Renal: Creatinine less than 2.0 mg/dL Pulmonary: DLCO greater than 60% Other: Not pregnant or nursing Fertile patients must use effective contraception No active Mycobacterium avium-intracellulare infection or CMV disease No cerebral toxoplasmosis or cryptococcal meningitis At least 6 months since prior alcohol or substance abuse At least 1 year since CNS disease or seizures No other medical condition that would preclude study PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics No concurrent chemotherapy for Kaposi's sarcoma Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified Other: At least 30 days since prior treatment for serious opportunistic infections
