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

Summary

Participation Requirements

Description

PRIMARY OBJECTIVES: 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 stud...

PRIMARY OBJECTIVES: 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. SECONDARY OBJECTIVES: 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. TERTIARY OBJECTIVES: 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.

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