RATIONALE: 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.

Condition	Treatment or Intervention	Phase
AIDS-related diffuse small cleaved cell lymphoma AIDS-related small noncleaved cell lymphoma AIDS-related lymphoblastic lymphoma AIDS-related diffuse mixed cell lymphoma AIDS-related immunoblastic large cell lymphoma AIDS-related peripheral/systemic lymphoma AIDS-related diffuse large cell lymphoma	Drug: RevM10 gene  Drug: RevM10/polAS gene	Phase I Phase II

Further Study Details: 

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.

PROTOCOL 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.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--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

--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

--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

Alabama
      University of Alabama Comprehensive Cancer Center, Birmingham,  Alabama,  35294,  United States
California
      Cedars-Sinai Medical Center, Los Angeles,  California,  90048,  United States
      Division of Oncology, Palo Alto,  California,  94304,  United States
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States
Massachusetts
      Massachusetts General Hospital Cancer Center, Boston,  Massachusetts,  02114,  United States
Nebraska
      University of Nebraska Medical Center, Omaha,  Nebraska,  68198-3330,  United States

Study chairs or principal investigators

Tyler Martin,  Study Chair,  Systemix   

Study ID Numbers:  CDR0000067135; SYSTEMIX-105; NCI-G99-1549; UCLA-HSPC-980303601D
Record last reviewed:  July 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003942
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08