A Phase I Study of Stem Cell Gene Therapy for HIV Mediated by Lentivector Transduced, Pre-Selected CD34+ Cells (AMC 097)
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What's the purpose of this trial?

This phase I/II trial studies the side effects and best dose of gene therapy in treating patients with human immunodeficiency virus (HIV)-related lymphoma that did not respond to therapy or came back after an original response receiving stem cell transplant. In gene therapy, small stretches of deoxyribonucleic acid (DNA) called "anti-HIV genes" are introduced into the stem cells in the laboratory to make the gene therapy product used in this study. The type of anti-HIV genes and therapy in this study may make the patient's immune cells more resistant to HIV-1 and prevent new immune cells from getting infected with HIV-1.

This trial is currently open and accepting patients.


What will happen during the trial?

This phase I/II trial studies the side effects and best dose of gene therapy in treating patients with human immunodeficiency virus (HIV)-related lymphoma that did not respond to therapy or came back after an original response receiving stem cell transplant. In gene therapy, small stretches of deoxyribonucleic acid (DNA) called "anti-HIV genes" are introduced into the stem cells in the laboratory to make the gene therapy product used in this study. The type of anti-HIV genes and therapy in this study may make the patient's immune cells more resistant to HIV-1 and prevent new immune cells from getting infected with HIV-1.

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

Inclusion Criteria:

  • Inclusion criteria associated with type and status of lymphoma
  • Biopsy-proven intermediate or high-grade non-Hodgkin's lymphoma, meeting one of the following criteria (timeline 4 months prior to start of trial):
    • 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 4 months prior to start of trial)
  • Biopsy-proven advanced stage mantle cell lymphoma with proliferation-related Ki-67 antigen (Ki-67) > 10% in first complete remission (timeline 4 months prior to start of trial)
  • Biopsy-proven Hodgkin's lymphoma, meeting one of the following criteria (timeline 4 months prior to start of trial)
    • 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 4 months prior to start of trial):
      • 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 anaplastic lymphoma kinase positive [ALK+] type in first or second complete remission) (timeline 4 months prior to start of trial)
  • INCLUSION CRITERIA ASSOCIATED WITH HIV-1 STATUS
  • HIV-1 infection, as documented by any federally approved, licensed HIV rapid test performed in conjunction with screening (or enzyme linked immunosorbent assay [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®)]), and have an HIV-1 viral load < 50 copies/mL by reverse transcriptase-polymerase chain reaction (RT-PCR) at the time of study enrollment; 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
  • Participants with CD4 counts > 50/microL are eligible for this study if their viral load is < 50 copies/mL by reverse transcription polymerase chain reaction (RT-PCR) since majority of the participants have received aggressive chemotherapy that can potentially decrease the CD4 counts despite the ART therapy; timeline: within 3 weeks prior to start of trial
  • GENERAL INCLUSION CRITERIA (TIMELINE: 8 WEEKS PRIOR TO START OF TRIAL, UNLESS OTHERWISE SPECIFIED)
  • Karnofsky performance status of 70-100%; Eastern Cooperative Oncology Group (ECOG) performance status =< [2]
  • Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) >= 2.5 times upper limit of normal (ULN)
  • Serum bilirubin =< 2.5 times ULN except for participants who are on atazanavir or indinavir, 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 gastroenterology service; timeline: within 3 weeks prior to start of trial
  • Participants with hepatitis B should be on appropriate anti-viral therapy at the time of the transplant, and their viral load should be under control; timeline: within 3 weeks prior to start of trial
  • Serum creatinine =< 2 times ULN; timeline: within 3 weeks prior to start of trial
  • Creatinine clearance >= 60 mL/min; timeline: within 3 weeks prior to start of trial
  • Prothrombin time (PT)/partial thromboplastin time (PTT) =< 2 times normal; timeline: within 3 weeks prior to start of trial
  • Forced expiratory volume in 1 second (FEV-1) or diffusion capacity of the lung for carbon monoxide (DLCO) >= 50% predicted; timeline: within 4 weeks prior to start of trial
  • Left ventricular ejection fraction (LVEF) >= 50% by 20-dimensional (20D) echocardiogram (ECHO) or multigated acquisition (MUGA) scan; timeline: within 4 weeks prior to start of trial
  • Not pregnant or nursing, with negative pregnancy test; timeline: within 3 weeks prior to start of trial
  • 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 start of trial

Exclusion Criteria:

  • Participants with > 5% involvement of bone marrow by malignant cells (either by manual count or flow cytometry) prior to stem cell collection
  • Participants with any abnormal cytogenetics in the bone marrow not related to the lymphoma, and not deemed to be constitutional
  • Participants with unexplained anemia, and/or thrombocytopenia
  • Participants with clear evidence of myeloproliferative disorders, or myelodysplastic disorders in the marrow
  • Presence of any active central nervous system (CNS) disease at the time of evaluation (parenchymal or leptomeningeal)
  • Any history of HIV-1 associated encephalopathy
  • History of other acquired immune deficiency syndrome (AIDS)-related syndromes that are perceived to cause excessive risk for morbidity post-transplantation, as determined by the principal investigator
  • Symptomatic/active bacterial, or fungal, or any other opportunistic infection
  • Active cytomegalovirus (CMV) retinitis, or other active CMV-related organ dysfunction
  • Relapse of pneumocystis carinii pneumonia within the past year
  • Intractable, severe diarrhea, defined as > 1.500 cc diarrheal fluid per day, or diarrhea causing persistent severe electrolyte abnormalities, or hypoalbuminemia
  • History of active myocardial ischemia, cardiomyopathy, uncontrolled dysrhythmia, or congestive heart failure within the last 6 months before the evaluation
  • Dementia of any kind
  • Seizures within the past 12 months
  • History of grade III hemorrhagic cystitis due to prior cyclophosphamide chemotherapy
  • History of other prior malignancy, except squamous cell carcinoma of the cervix or anus, superficial basal cell or squamous cell skin cancer, or other malignancy curatively treated more than 5 years ago
  • Active psychosocial condition that would hinder study compliance and follow-up
  • Any perceived inability to directly (and without the means of a legal guardian) provide informed consent
  • Any medical or physical contraindication, or other inability to undergo hematopoietic progenitor cell (HPC) collection
  • Participants who are receiving any other investigational agents
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued; these potential risks may also apply to other agents used in this study

Additional Trial Information

Phase 1/2

Enrollment: 18 patients (estimated)

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Trial Locations

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New York

Memorial Sloan Kettering Cancer Center

New York, NY

Open and Accepting
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