Condition or disease | Intervention/treatment | Phase |
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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 | Procedure: Autologous Hematopoietic Stem Cell Transplantation Drug: Carmustine Drug: Cytarabine Drug: Etoposide Other: Laboratory Biomarker Analysis Biological: Lentivirus Vector CCR5 shRNA/TRIM5alpha/TAR Decoy-transduced Autologous CD34-positive Hematopoietic Progenitor Cells Drug: Melphalan Procedure: Peripheral Blood Stem Cell Transplantation | Phase 1 Phase 2 |
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.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 18 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Stem Cell Gene Therapy for HIV Mediated by Lentivector Transduced, Pre-selected CD34+ Cells |
Actual Study Start Date : | June 23, 2016 |
Estimated Primary Completion Date : | September 30, 2022 |
Estimated Study Completion Date : | September 30, 2024 |
Arm | Intervention/treatment |
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Experimental: Treatment (anti-HIV gene transduced CD34+ cells)
Patients receive BEAM regimen administered as standard of care comprising carmustine on day -6, cytarabine 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.
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Procedure: Autologous Hematopoietic Stem Cell Transplantation
Undergo infusion of lentivirus vector CCR5 shRNA/TRIM5alpha/TAR decoy-transduced autologous CD34-positive hematopoietic progenitor cells
Other Name: Autologous Stem Cell Transplantation
Drug: Carmustine 300 mg/m2 on Day -6, as part of BEAM and R-BEAM regimens.
Other Names:
Drug: Cytarabine 100 mg/m2 BID on Days -5 through -2, as part of BEAM and R-BEAM regimens.
Other Names:
Drug: Etoposide VP-16: 100 mg/m2 BID on Days -5 through -2, as part of BEAM and R-BEAM regimens.
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies
Biological: Lentivirus Vector CCR5 shRNA/TRIM5alpha/TAR Decoy-transduced Autologous CD34-positive Hematopoietic Progenitor Cells Undergo infusion of lentivirus vector CCR5 shRNA/TRIM5alpha/TAR decoy-transduced autologous CD34-positive hematopoietic progenitor cells
Other Name: Lentivirus Vector CCR5 shRNA/TRIM5alpha/TAR Decoy-transduced Autologous CD34-positive HPCs
Drug: Melphalan 140 mg/m2 on Day -1, as part of BEAM and R-BEAM regimens.
Other Names:
Procedure: Peripheral Blood Stem Cell Transplantation Undergo infusion of lentivirus vector CCR5 shRNA/TRIM5alpha/TAR decoy-transduced autologous CD34-positive hematopoietic progenitor cells
Other Names:
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First measurement of 3 consecutive laboratory values obtained on different days) of ANC > 500 cells/mm3
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Ages Eligible for Study: | 19 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Biopsy-proven intermediate or high-grade non-Hodgkin's lymphoma, meeting one of the following criteria (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)
Biopsy-proven Burkitt's lymphoma, meeting one of the following criteria (timeline 4 months prior to start of trial):
Exclusion Criteria:
United States, California | |
UC San Diego Moores Cancer Center | Recruiting |
La Jolla, California, United States, 92093 | |
Contact: Jesika Reiner, MPH 858-822-5364 jreiner@ucsd.edu | |
Principal Investigator: Matthew Wieduwilt, MD, PhD | |
University of California Davis Comprehensive Cancer Center | Recruiting |
Sacramento, California, United States, 95817 | |
Contact: Deborah Stewart, CCRP 916-703-9118 distewart@ucdavis.edu | |
Principal Investigator: Mehrdad Abedi, MD | |
UCSF Medical Center-Parnassus | Recruiting |
San Francisco, California, United States, 94115 | |
Contact: Jenai Wilmoth, RN 415-514-6281 Jenai.Wilmoth@ucsf.edu | |
Principal Investigator: Lawrence Kaplan, MD | |
United States, New York | |
Memorial Sloan Kettering Cancer Center | Recruiting |
New York, New York, United States, 10065 | |
Contact: Craig Sauter, MD sauterc@mskcc.org | |
Principal Investigator: Craig Sauter |
Principal Investigator: | Mehrdad Abedi | AIDS Malignancy Consortium |
Tracking Information | ||||
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First Submitted Date ICMJE | June 8, 2016 | |||
First Posted Date ICMJE | June 13, 2016 | |||
Last Update Posted Date | April 2, 2021 | |||
Actual Study Start Date ICMJE | June 23, 2016 | |||
Estimated Primary Completion Date | September 30, 2022 (Final data collection date for primary outcome measure) | |||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE | Same as current | |||
Change History | ||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures |
Expansion of HIV-1 resistant immune cells [ Time Frame: Up to 24 months post-transplant ] 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 ART
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Original Other Pre-specified Outcome Measures |
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 ART [ Time Frame: Up to 24 months post-transplant ] | |||
Descriptive Information | ||||
Brief Title ICMJE | Gene Therapy in Treating Patients With Human Immunodeficiency Virus-Related Lymphoma Receiving Stem Cell Transplant | |||
Official Title ICMJE | Stem Cell Gene Therapy for HIV Mediated by Lentivector Transduced, Pre-selected CD34+ Cells | |||
Brief Summary | 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. | |||
Detailed 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 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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Study Type ICMJE | Interventional | |||
Study Phase ICMJE | Phase 1 Phase 2 |
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Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE | Experimental: Treatment (anti-HIV gene transduced CD34+ cells)
Patients receive BEAM regimen administered as standard of care comprising carmustine on day -6, cytarabine 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.
Interventions:
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Publications * | Not Provided | |||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | ||||
Recruitment Status ICMJE | Recruiting | |||
Estimated Enrollment ICMJE |
18 | |||
Original Estimated Enrollment ICMJE | Same as current | |||
Estimated Study Completion Date ICMJE | September 30, 2024 | |||
Estimated Primary Completion Date | September 30, 2022 (Final data collection date for primary outcome measure) | |||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 19 Years and older (Adult, Older Adult) | |||
Accepts Healthy Volunteers ICMJE | No | |||
Contacts ICMJE | ||||
Listed Location Countries ICMJE | United States | |||
Removed Location Countries | ||||
Administrative Information | ||||
NCT Number ICMJE | NCT02797470 | |||
Other Study ID Numbers ICMJE | AMC-097 NCI-2015-01745 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 9933 ( Other Identifier: CTRP (Clinical Trial Reporting Program) ) AMC 097 ( Other Identifier: AIDS Malignancy Consortium ) 097 ( Other Identifier: AIDS Malignancy Consortium ) AMC-097 ( Other Identifier: CTEP ) U01CA121947 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | Yes | |||
U.S. FDA-regulated Product | Not Provided | |||
IPD Sharing Statement ICMJE |
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Responsible Party | AIDS Malignancy Consortium | |||
Study Sponsor ICMJE | AIDS Malignancy Consortium | |||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | AIDS Malignancy Consortium | |||
Verification Date | March 2021 | |||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |