Observational Study of People Living With HIV Treated With CD19-directed CAR T Cell (CS22-03)

Observational Cohort Study of People Living With HIV Treated With CD19-directed CAR T Cell Therapy for B-cell Lymphoid Malignancies

This protocol will develop an observational cohort of PLWH who have been or are being treated with CAR19 therapy outside of an AMC clinical trial. Following regulatory approval of this protocol, sites will be asked to capture information of participants, who carry a diagnosis of HIV disease AND received CAR19 therapy outside of a clinical trial between August 30, 2017 and August 31, 2021. Data captured will include data points are available as part of standard of care for participants undergoing CAR19 therapy. AMC investigators, as well as non-AMC investigators will identify eligible participants to the CIBMTR, who in turn will provide the AMC statistical center with de-identified data

Study Overview

• Status: Completed
• Conditions: HIV Infections; Lymphoma, Follicular; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Follicular Lymphoma; Leukemia; Leukemia, Lymphoblastic; HIV Associated Lymphoma; HIV Disease; Lymphoma

Detailed Description

Two landmark trials have led to the FDA approval of two different CD19 directed chimeric antigen receptor (CAR) T cell (CAR19) products in the United States for the treatment of relapsed or refractory (RR) large B-cell lymphoma after two or more lines of systemic therapy: tisagenlecleucel (Kymriah™) and axicabtagene ciloleucel (Yescarta ®). In the ZUMA-1 registration trial for axicabtagene ciloleucel (axi-cel), 42% of the 101 treated patients achieved a complete response (CR), and with a median follow up of 15 months, the projected 1year progression free survival (PFS) was 70%. In a recent updated analysis, the CR rate was 58% with about 40% of patients having durable remissions at 2 years of follow up. Similar results were seen in the JULIET registrational trial for tisagenlecleucel (tisa-cel) with an overall response rate (ORR) of 52%, and a CR rate of 40% in the 93 patients evaluable for response; with a median follow up of 14 months, the estimated 12-months relapse-free survival was 65% (79% among patients with a CR). Tisagenlecleucel is also approved for the treatment of acute B-lineage lymphoblastic leukemia in patients up to the age of 25 years. Unfortunately, in both trials patients with known HIV infection were excluded. Therefore, no safety or efficacy data for treatment with CAR19 in PLWH exists, and access for PLWH in the US to this potentially curative treatment has been limited.

This has to be contrasted with the fact that malignancies, and specifically lymphomas, remain a major contributor to early mortality in PLWH. With a lifetime risk of cancer ranging between 24-40%, the leading cause of death in PLWH in economically developed countries is cancer, and the most common cancer in PLWH in the US remains Non-Hodgkin lymphoma (NHL). While early during the HIV epidemic, outcomes for PLWH and aggressive B-cell lymphomas were significantly worse compared to immunocompetent patients, this is no longer the case for the majority of PLWH, owing mainly to effective antiretroviral therapies leading to better tolerance of myelosuppressive chemotherapy and a consequent paradigm shift in aggressive therapies for HIV-associated lymphoma. It has been repeatedly demonstrated that PLWH have been able to safely tolerate aggressive high-dose chemotherapy, as well as autologous and even allogeneic hematopoietic cell transplant.

• Study Type: Observational
• Enrollment (Actual): 30

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19106
      • Pennsylvania Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

People living with HIV treated with CD19-directed CAR T cell therapy for B-cell lymphoid malignancies

Description

Inclusion Criteria:

• Documented history of HIV infection
• Received CD19-directed CAR T cell therapy for acute lymphoblastic leukemia, diffuse large B-cell lymphoma, high-grade B-cell lymphoma, transformed follicular lymphoma, or primary mediastinal B-cell lymphoma
• Age ≥ 18 years

Exclusion Criteria:

• Prior treatment with any CAR T cell therapy

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Observational; Clinical information on participants, who carry a diagnosis of HIV disease AND received CAR19 therapy outside of a clinical trial between August 30, 2017 and August 31, 2021 will be captured

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of toxicities related to CAR19 therapy	Toxicities related to CAR19 therapy will be reported by Common Terminology for Adverse Events (CTCAE) criteria, as well as American Society for Transplantation and Cellular Therapy (ASTCT) criteria (for cytokine release syndrome)	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in CD4 count	CD4 count on day of leukapheresis, 3 months post CAR19 therapy, 6 months post CAR19 therapy, and 12-months post therapy will be measured	Day 0, 3 months, 6 months, and 12 months post CAR19 therapy
Absolute lymphocyte count	Absolute lymphocyte count on day of leukapheresis, 3 months post CAR19 therapy, 6 months post CAR19 therapy, and 12-months post therapy will be measured	Day 0, 3 months, 6 months, and 12 months post CAR19 therapy
HIV viral load	HIV viral load on day of leukapheresis, 3 months post CAR19 therapy, 6 months post CAR19 therapy, and 12-months post therapy will be measured	Day 0, 3 months, 6 months, and 12 months post CAR19 therapy
Overall response	Defined as complete remission plus partial remission	3 months and 6 months
Complete remission	Defined as complete disappearance of all disease	3 months and 6 months

Collaborators and Investigators

• Sponsor: AIDS Malignancy Consortium
• Collaborators: Center for International Blood and Marrow Transplant Research

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2021
• Primary Completion (Actual): November 14, 2024
• Study Completion (Actual): November 14, 2024

Study Registration Dates

• First Submitted: March 13, 2023
• First Submitted That Met QC Criteria: March 23, 2023
• First Posted (Actual): March 24, 2023

Study Record Updates

• Last Update Posted (Actual): February 2, 2026
• Last Update Submitted That Met QC Criteria: January 29, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: CAR T-cell therapy; B-cell lymphoma; acute lymphoblastic leukemia; CART cell therapy
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Neoplasms; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Slow Virus Diseases; Leukemia, Lymphoid; Hemic and Lymphatic Diseases; HIV Infections; Leukemia; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Acquired Immunodeficiency Syndrome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, Follicular; Lymphoma, Primary Effusion
• Other Study ID Numbers: AMC-113

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes