Gene Therapy in Treating Patients With Human Immunodeficiency Virus-Related Lymphoma Receiving Stem Cell Transplant

Inclusion Criteria

• •* Biopsy-proven intermediate or high-grade non-Hodgkin's lymphoma, meeting one of the following criteria (timeline 8 months prior to enrollment in the screening segment):
• •\- In partial remission,
• •\- Relapsed after initial complete remission,
• •\- Failed induction therapy, but responds to salvage therapy (i.e., chemosensitive disease),
• •\- In complete remission with high-risk features as specified by the International Prognostic Index.
• •* Biopsy-proven advanced stage follicular lymphoma, that have failed at least two lines of therapy multi-agent chemotherapy, but responds to salvage therapy i.e.,chemosensitive disease) (timeline 8 months prior to enrollment in the screening segment).
• •* Biopsy-proven advanced stage Mantle cell lymphoma with Ki-67 \> 10% in first complete remission (timeline 8 months prior to enrollment in the screening segment).
• •* Biopsy-proven Hodgkin's lymphoma, meeting one of the following criteria (timeline 8 months prior to enrollment).
• •\- In first, or greater relapse after initial complete remission,
• •\- In partial remission,
• •\- Failed induction therapy, but responds to salvage therapy (i.e., chemosensitive disease).
• •* Biopsy-proven Burkitt's lymphoma, meeting one of the following criteria (timeline 8 months prior to enrollment):
• •\- In second complete remission after relapse following initial complete remission,
• •\- Failed induction therapy, but responds (very good partial remission, complete remission, or near complete remission) to salvage therapy (i.e., chemosensitive disease).
• •* Biopsy proven plasmablastic lymphomas, or peripheral T cell lymphoma (with the exception of ALK+ type in first or second complete remission) \*NOTE: Patients meeting the following criteria are exempt from the 8-month timeline and do not require additional biopsy:
• •* Patients who have never achieved a complete remission on the last biopsy-proven site of disease and went on to the next therapy then achieved a complete remission.
• •* Patients who relapsed quickly (within 3 months of their last chemotherapy) and now have achieved a complete remission with salvage therapy.
• •* HIV-1 infection, as documented by any federally approved, licensed HIV rapid test performed in conjunction with screening (or ELISA, test kit, and confirmed by Western blot or other approved test). Alternatively, this documentation may include a record demonstrating that another physician has documented the participant's HIV status based on either: 1) approved diagnostic tests, or 2) the referring physician's written record that HIV infection was documented, with supporting information on the participant's relevant medical history and/or current management of HIV infection.
• •* Must be on a multi-drug anti-HIV regimen (excluding zidovudine \[AZT, ZDV, Retrovir®, or agents containing zidovudine (e.g., Combivir® and Trizivir®)\], and efavirenz \[Sustiva®, or agents containing efavirenz (e.g., Atripla®)\]).
• •Participants on zidovudine \[AZT, ZDV, Retrovir®; including Combivir® and Trizivir®\] and efavirenz \[Sustiva®; including Atripla®\] must switch to an alternative regimen without anticipated drug-drug interactions or myelosuppressive properties based on known viral resistance patterns and/or ART history, such as raltegravir and Truvada (emtricitabine and tenofovir) at least two weeks prior to the transplant.
• •o Participant taking ARTs must satisfy one of the following:
• •Undetectable HIV viral load (\< 50 copies/mL). For patients who have had negative viral loads in the past 6 months and no known HIV viral load \>500 copies/mL within the last 6 months, minor fluctuations of viral load (isolated escalations up to 500 copies/mL) are acceptable. The participant's history of negative viral loads may be documented with recent laboratory results and/or a record from the participant's HIV care provider.
• •If viral load is detectable at \< 2000 copies/mL a review of previous antiretroviral regimens or previous genotypic or phenotypic testing which indicate the ability to fully suppress virus by addition of sensitive drugs must be performed. This review will be carried out by the protocol ID team or the ID specialist caring for the patient.
• •If viral load is detectable at ≥ 2000 copies/mL, a current HIV genotype and/or phenotype must be obtained. If a HAART regimen to which the patient's virus is sensitive can be determined based on genotype and previous antiretroviral experience, then the patient will be considered eligible in this regard. This review will be carried out by the protocol ID team or the ID specialist caring for the patient.
• •Karnofsky performance status of 70-100%. ECOG performance status \<2
• •SGOT and SGPT ≤ 2.5 times upper limit of normal (ULN). Serum bilirubin ≤ 2.5 times ULN except for participants who are on atazanavir or indinavir, or with elevated indirect bilirubin related to bilirubin conjugation issues such as Gilbert's disease, provided that the participant's direct bilirubin is within normal institutional limits.
• •Participants who are hepatitis C virus antibody positive, or hepatitis B virus surface antigen positive must be free of clinical evidence of cirrhosis as determined by the principal investigator in consultation with the institutional Gastroenterology Service.
• •Participants with Hepatitis B should be on appropriate anti-viral therapy at the time of the transplant, and their viral load should be negative.
• •Serum creatinine ≤ 2 times ULN.
• •Creatinine clearance ≥ 60 mL/min by the modified Cockcroft-Gault Formula.
• •PT/PTT ≤ 2 times upper limit of normal (ULN), or international normalized ratio (INR)/PTT ≤ 2 times the ULN.
• •FEV-1 or DLCO (corrected for hemoglobin) ≥ 50% predicted.
• •LVEF ≥ 50% by 2D ECHO or MUGA scan.
• •Not pregnant or nursing, with negative serum pregnancy test. Pregnant women are excluded from this study because the conditioning regimen has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with BEAM, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study.
• •Participants should agree to practice effective contraceptive precautions and to use at least one method of contraception for the duration of the study and for 3 months post-transplant.
• •Age ≥18 years. Because only adult transplant centers are participating as study sites.
• •* Life expectancy of greater than 3 months.
• •* Ability to understand and the willingness to sign a written informed consent document.
• •* Receipt of a stable ART regimen for at least 3 weeks prior to enrollment.