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.
Stem Cell Gene Therapy for HIV Mediated by Lentivector Transduced, Pre-selected CD34+ Cells
I. Safety, defined as timely engraftment (the collective establishment of a persistent absolute neutrophil count of at least 500 cells/mm^3 and platelet count of 20,000 cells/mm^3 without transfusion for 3 consecutive days) at one month post transplant, in the absence of any study candidate specific grade 3 and 4 non-hematopoietic organ toxicity or any clonal expansion.
II. Efficacy of the candidate product, defined as establishment of> 5% mononuclear blood cells expressing anti-HIV genes in the peripheral blood at 3 months post-transplant.
I. To determine the presence, quantity, and duration of gene modified HIV-1 resistant peripheral blood cells and gut mucosal immune cells.
II. To study the integration sites of vector sequences in circulating cells. III. To study progression-free survival. IV. To study overall survival. V. To study complete response rate and duration. VI. To study partial response rate and duration. VII. To study time to neutrophil engraftment (first of 3 consecutive days of absolute neutrophil count [ANC]> 500 cells/mm^3).
VIII. To study time to platelet engraftment (first of 3 consecutive days of platelets> 20,000 cells/mm^3 without platelet transfusions 7 days prior).
IX. To study hematologic function at day 100 (ANC> 1500, hemoglobin [Hb]> 10 g/dl without transfusion and platelets> 100,000) X. To study cluster of differentiation (CD)4 recovery at the conclusion of the trial.
XI. To study safety in terms of toxicities, infections, transfusions, and infusion-related reactions.
XII. To study HIV-1 viral load over time. XIII. To study persistence of vector-transduced cells over time.
I. To evaluate the presence and the magnitude of expansion of HIV-1 resistant immune cells in the peripheral blood and gut mucosa of transplanted participants, subsequent to withholding anti-retroviral therapy (ART).
OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.
Patients receive BEAM regimen administered as standard of care comprising carmustine on day -6, cytarabine twice daily (BID) on days -5 to -2, etoposide BID on days -5 to -2, and melphalan on day -1. Patients undergo infusion of lentivirus vector CCR5 shRNA/TRIM5alpha/TAR decoy-transduced autologous CD34-positive hematopoietic progenitor cells over 1 hour.
After completion of study treatment, patients are followed up at days 7, 14, 21, 28, 42, 60, 90, 120, 180, 240, 300, 360, 420, 480, 520, 600, 660, and 720, and then yearly for at least 15 years.
HIV Infection Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma Plasmablastic Lymphoma Recurrent Adult Hodgkin Lymphoma Recurrent Adult Non-Hodgkin Lymphoma Recurrent Burkitt Lymphoma Recurrent Follicular Lymphoma Stage III Follicular Lymphoma Stage III Mantle Cell Lymphoma Stage IV Follicular Lymphoma Stage IV Mantle Cell Lymphoma Melphalan Carmustine Mechlorethamine Nitrogen Mustard Compounds Etoposide phosphate Etoposide Cytarabine Podophyllotoxin
Open to people ages 19 years and up
We will not share your information with anyone other than the team in charge of this study. Submitting your contact information does not obligate you to participate in research.
The study team should get back to you in a few business days.
You will also receive an email with next steps. Check your junk/spam folder if needed.
If you do not hear from the study team, please call 888-689-8273 and tell them you’re interested in study number NCT02797470.
© 2017 The Regents of the University of California