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

NCT02797470 | Active Not Recruiting Phase 1 Results DMC

• 6 other identifiers: AMC-097NCI-2015-017459933AMC 097097U01CA121947
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 4

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Achieve a Timely Engraftment

  Timely engraftment is defined as a persistent an absolute neutrophil count (ANC) of at least 500 cells/mm3 and a platelet count of at least 20,000 cells/mm3 for at least 3 days

  1 month post-transplant

Secondary Outcomes (16)

• Proportion of Study Participants Who Achieve Greater Than 5% Mononuclear Blood Cells Expressing Anti-HIV Genes in Peripheral Blood

  3 months post-transplant

• Proportion of Study Participants With Gene Modified HIV-1 Resistant Peripheral Blood Cells and Gut Mucosal Immune Cells

  Up to 24 months post-transplant

• Quantity of Gene Modified HIV-1 Resistant Peripheral Blood Cells and Gut Mucosal Immune Cells

  Up to 24 months post-transplant

• Integration Sites of Vector Sequences in Circulating Cells

  Up to 24 months post-transplant

• Progression-free Survival

  Time from start of study treatment to relapse, progression, or death from any cause

Other Outcomes (1)

• Expansion of HIV-1 Resistant Immune Cells

  Up to 24 months post-transplant

Study Arms (1)

Treatment (anti-HIV gene transduced CD34+ cells)

EXPERIMENTAL

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.

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

Interventions

Autologous Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo infusion of lentivirus vector CCR5 shRNA/TRIM5alpha/TAR decoy-transduced autologous CD34-positive hematopoietic progenitor cells

Also known as: Autologous Stem Cell Transplantation

Treatment (anti-HIV gene transduced CD34+ cells)

Carmustine DRUG

300 mg/m2 on Day -6, as part of BEAM and R-BEAM regimens.

Also known as: BCNU, Becenum, Becenun, BiCNU, Bis(chloroethyl) Nitrosourea, Bis-Chloronitrosourea, Carmubris, Carmustin, Carmustinum, FDA 0345, Gliadel, N,N'-Bis(2-chloroethyl)-N-nitrosourea, Nitrourean, Nitrumon, SK 27702, SRI 1720, WR-139021

Treatment (anti-HIV gene transduced CD34+ cells)

Cytarabine DRUG

100 mg/m2 BID on Days -5 through -2, as part of BEAM and R-BEAM regimens.

Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosar-U, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Treatment (anti-HIV gene transduced CD34+ cells)

Etoposide DRUG

VP-16: 100 mg/m2 BID on Days -5 through -2, as part of BEAM and R-BEAM regimens.

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16-213, VP-16, VP-16-213

Treatment (anti-HIV gene transduced CD34+ cells)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (anti-HIV gene transduced CD34+ cells)

Lentivirus Vector CCR5 shRNA/TRIM5alpha/TAR Decoy-transduced Autologous CD34-positive Hematopoietic Progenitor Cells BIOLOGICAL

Undergo infusion of lentivirus vector CCR5 shRNA/TRIM5alpha/TAR decoy-transduced autologous CD34-positive hematopoietic progenitor cells

Also known as: Lentivirus Vector CCR5 shRNA/TRIM5alpha/TAR Decoy-transduced Autologous CD34-positive HPCs

Treatment (anti-HIV gene transduced CD34+ cells)

Melphalan DRUG

140 mg/m2 on Day -1, as part of BEAM and R-BEAM regimens.

Also known as: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard, L-Sarcolysin, L-Sarcolysin Phenylalanine mustard, L-Sarcolysine, Melphalanum, Phenylalanine Mustard, Phenylalanine Nitrogen Mustard, Sarcoclorin, Sarkolysin, WR-19813

Treatment (anti-HIV gene transduced CD34+ cells)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo infusion of lentivirus vector CCR5 shRNA/TRIM5alpha/TAR decoy-transduced autologous CD34-positive hematopoietic progenitor cells

Also known as: PBPC transplantation, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplantation

Treatment (anti-HIV gene transduced CD34+ cells)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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 CNS disease at the time of evaluation (parenchymal or leptomeningeal).
• Any history of HIV-1 associated encephalopathy.
• Participants with persistently low CD4 counts less than 200 and a history of any AIDS-defining infection in the last 6 months before screening are excluded from the study.
• Symptomatic/active bacterial, or fungal, or any other opportunistic infection.
• Active CMV retinitis, or other active CMV-related organ dysfunction.
• Relapse of pneumocystis carinii pneumonia within the past year before enrollment.
• 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 enrollment.
• Dementia of any kind.
• Seizures within the past 12 months before enrollment.
• History of Grade III hemorrhagic cystitis due to prior cyclophosphamide chemotherapy.

Sponsors & Collaborators

• AIDS Malignancy Consortium: lead
• National Cancer Institute (NCI): collaborator
• California Institute for Regenerative Medicine (CIRM): collaborator

Study Sites (4)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

UCSF Medical Center-Parnassus

San Francisco, California, 94115, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

HIV Infections; Lymphoma, T-Cell; Plasmablastic Lymphoma; Hodgkin Disease; Lymphoma, Non-Hodgkin; Burkitt Lymphoma; Lymphoma, Follicular; Lymphoma, Mantle-Cell

Interventions

Carmustine; carmustine, poliferprosan 20 drug combination; Cytarabine; Etoposide; Melphalan; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Large B-Cell, Diffuse; Lymphoma, B-Cell; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Tumor Virus Infections

Intervention Hierarchy (Ancestors)

Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Deukwoo Kwon
• Organization: Statistical and Data Analysis Center, AIDS Malignancy Consortium

deukwoo.kwon@mountsinai.org

(713) 500-7964

Study Officials

• Mehrdad Abedi

  AIDS Malignancy Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2016
• First Posted: June 13, 2016
• Study Start: June 23, 2016
• Primary Completion: May 13, 2021
• Study Completion (Estimated): March 1, 2036
• Last Updated: April 20, 2025
• Results First Posted: July 20, 2023

Record last verified: 2025-04

Locations

US (4)