Genetically Modified Peripheral Blood Stem Cell Transplant in Treating Patients With HIV-Associated Non-Hodgkin or Hodgkin Lymphoma
Adult Nasal Type Extranodal NK/T-cell Lymphoma, AIDS-related Diffuse Large Cell Lymphoma, AIDS-related Diffuse Mixed Cell Lymphoma
About this trial
This is an interventional treatment trial for Adult Nasal Type Extranodal NK/T-cell Lymphoma
Eligibility Criteria
Inclusion Criteria:
- HIV seropositive
- Antiretroviral treatment for at least one month, defined as a multi-drug regimen (excluding azacitidine [AZT])
- HIV plasma viral load has decreased by 1.5 logs or viral load < 5000 copies/ml
Non-Hodgkin or Hodgkin lymphoma without active central nervous system (CNS) involvement associated with poor prognosis with medical therapy alone or for which autologous peripheral blood stem cell (PBSC) transplant is indicated:
- Hodgkin's lymphoma beyond first remission; first partial remission; induction failure with subsequent response to salvage therapy
- Non-Hodgkin's Lymphoma beyond first remission: first partial remission; induction failure with subsequent response to salvage therapy
- Chemotherapy responsive disease
- Karnofsky performance score >= 70%
- Subjects must agree to use effective contraception from enrollment through completion of the study
- Female subjects: if of child bearing potential, must have negative serum or urine pregnancy test within 7 days of treatment
- Subjects must be on a prophylactic regimen for Pneumocystis carinii pneumonia, or agree to begin such treatment, if the cluster of differentiation (CD)4 counts are =< 200
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
- Serum creatinine > 2 times upper limit of normal
- Serum bilirubin greater than 3 times the upper limits of normal, unless determined to be a result of the primary hematologic malignancy or attributed to Gilbert's syndrome
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 times the upper limits of normal, unless determined to be a result of the primary hematologic malignancy or attributed to Gilbert's syndrome
- Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) or diffusion capacity of the lung of carbon monoxide (DLCO) parameters < 60% predicted (corrected for hemoglobin)
- Left ventricular ejection fraction (LVEF) < 50% or coronary artery disease requiring treatment
- Active infection requiring systemic antibiotic therapy with antibacterial, antifungal, or antiviral agents (excluding HIV)
- Patients who are hepatitis C virus (HCV) antibody positive or hepatitis B virus (HBV) surface antigen positive must be free of clinical evidence of cirrhosis that would otherwise make them ineligible for HCT, as determined by the Principal Investigator (P.I.) in consultation with the Gastrointestinal Service; patients with HBV and ongoing evidence of viral replication may require therapy prior to receiving high-dose chemotherapy
- Positive serology for Toxoplasma gondii AND requiring treatment or with evidence of active infection
- Malignancy other than lymphoma, unless 1) in complete remission and more than 5 years from last treatment), or 2) cervical/anal squamous cell carcinoma in situ or 3) superficial basal cell and squamous cell cancers of the skin
- History of HIV-associated encephalopathy; dementia of any kind; seizures in the past 12 months; any perceived inability to directly provide informed consent (Note: Consent may not be obtained by means of a legal guardian)
- A medical history of noncompliance with highly active anti-retroviral therapy (HAART) or medical therapy
Sites / Locations
- Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Arms of the Study
Arm 1
Experimental
Treatment (gene modified peripheral blood cell transplant)
CONDITIONING: Patients receive carmustine IV over 3 hours on day -7, cytarabine IV over 2 hours BID and etoposide IV over 2 hours BID on days -6 to -3, and melphalan IV over 30 minutes on day -2. TRANSPLANTATION: Patients receive an autologous PBSC infusion and/or infusion of autologous transduced hematopoietic cells on day 0. Beginning 28-120 days later, patients eligible for in vivo selection after detection of gene-marked cells receive O6-benzylguanine IV over 1 hour and carmustine IV over 3 hours on days 14, 28, and then monthly until completion of therapy. Patients achieving > 10% gene marking and CD4 count of >= 500 cells/uL receive up to 2 courses of structured treatment interruption without undergoing in vivo selection.