Immune Cell Therapy (CAR-T) for the Treatment of Patients With HIV and B-Cell Non-Hodgkin Lymphoma

NCT05077527 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: AMC-112NCI-2021-02771UM1CA121947
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 6

Brief Summary

This phase I trial evaluates the side effects and usefulness of axicabtagene clioleucel (a CAR-T therapy) and find out what effect, if any, it has on treating patients with HIV-associated aggressive B-cell non-Hodgkin lymphoma that has come back (relapsed) or not responded to treatment (refractory). T cells are infection fighting blood cells that can kill tumor cells. Axicabtagene ciloleucel consists of genetically modified T cells, modified to recognize CD-19, a protein on the surface of cancer cells. These CD-19-specific T cells may help the body's immune system identify and kill CD-19-positive B-cell non-Hodgkin lymphoma cells.

Conditions

AIDS-Related Diffuse Large B-cell Lymphoma; AIDS-Related Non-Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Primary Mediastinal (Thymic) Large B-Cell Lymphoma; Refractory High Grade B-Cell Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Transformed B-Cell Non-Hodgkin Lymphoma; HIV Infection; Recurrent Grade 3b Follicular Lymphoma; Recurrent High Grade B-Cell Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Transformed B-Cell Non-Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Grade 3b Follicular Lymphoma; Refractory Primary Mediastinal (Thymic) Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Safety of chimeric antigen receptor (CAR) T-cell therapy

  Safety defined as blood count recovery of neutrophils and platelets to grade 2 or less within 6 weeks of CAR-T cell administration; incidence of infections; and cytokine release syndrome as defined by the 2019 American Society for Transplantation and Cellular Therapy harmonized system. The incidence of toxicity will be summarized using frequency and percentage and presented by overall and for each CD4 cohort.

  Up to 2 years

• Feasibility of CAR-T Therapy

  Feasibility defined as ability of enrolled participants in each cohort to receive axicabtagene ciloleucel. Feasibility will be estimated as the proportion of participants who receive axicabtagene ciloleucel among all enrolled participants who undergo leukapheresis. A two-sided 95% exact confidence interval will also be reported together with the estimated proportion. Production failure will be defined as the number of episodes of "inability to collect sufficient T-cells and/or create products." It will be summarized using descriptive statistics.

  Up to 2 years

Secondary Outcomes (4)

• Complete response rate

  Up to 2 years

• Event-free survival (EFS)

  From time from randomization to earliest date of disease progression, commencement of new lymphoma therapy, or death, assessed up to 2 years

• Duration of response (DOR)

  From time when response criteria are met to the documentation of relapse or progression, assessed up to 2 years

• CD4 and CD8 counts

  Up to 2 years

Other Outcomes (2)

• Relationship between immune-mediated response and clinical response and toxicity in human immundeficiency virus (HIV)-associated B-Cell Non-Hodgkin Lymphoma treated with axicabtagene ciloleucel

  Up to 2 years

• Burden of HIV integration in the final CAR T-cell product versus the pheresis product through quantitative polymerase chain reaction

  Up to 2 years

Study Arms (1)

Treatment (conditioning, axicabtagene ciloleucel)

EXPERIMENTAL

Patients receive fludarabine IV over 30 minutes and cyclophosphamide IV over 1 hour on days -5, -4, and -3. Patients then receive axicabtagene ciloleucel IV over 30 minutes on day 0.

Biological: Axicabtagene Ciloleucel; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

Axicabtagene Ciloleucel BIOLOGICAL

Given IV

Also known as: KTE C19, KTE-C19, KTE-C19 CAR, Yescarta

Treatment (conditioning, axicabtagene ciloleucel)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (conditioning, axicabtagene ciloleucel)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (conditioning, axicabtagene ciloleucel)

Eligibility Criteria

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

You may qualify if:

• Participant with age \>= 18 years at the time of consent. Because no dosing or adverse event data are currently available on the use of axicabtagene ciloleucel in participants \< 18 years of age, children are excluded from this study
• Participant is able to understand and willing to sign a written informed consent document before any study procedures
• Participant must have R/R aggressive B-cell NHL of the following histologies:
• Diffuse large B-cell lymphoma (DLBCL, including transformed from indolent histology)
• High-grade B-cell lymphoma
• Primary mediastinal B-cell lymphoma
• Follicular lymphoma, grade 3B
• Participant must have been treated with an anthracycline and rituximab (or other CD20-targeted agent) and have R/R disease after at least 2 lines of therapy
• At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic cancer therapy at the time the subject provides consent
• Evaluable disease as either:
• Positron emission tomography (PET)-positive disease according to the "Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification", or
• Bone marrow involvement assessed by bone marrow biopsy
• Eastern Cooperative Oncology Group ECOG performance status =\< 1 (Karnofsky \>= 60%)
• Serum creatinine =\< 1.5 x age-adjusted upper limit of normal (ULN) OR calculated creatinine clearance (Cockcroft and Gault) \> 30 mL/min/1.73 m\^2 (within 4 weeks before enrollment)
• Alanine aminotransferase (ALT) =\< 5 x ULN and total bilirubin \< 2.0 mg/dL (or \< 3.0 mg/dL for subjects with Gilbert's syndrome or lymphomatous infiltration of the liver or if taking atazanavir or indinavir (within 4 weeks before enrollment)

You may not qualify if:

• Participants felt to have a high prospect of clinically benefiting from autologous transplantation
• Participants with central nervous system (CNS)-only involvement by malignancy (note: participants with secondary CNS involvement are allowed on study
• Participants with a second prior or concurrent malignancy that, in the opinion of the investigator, has a natural history or treatment course that has the potential to interfere with the safety or efficacy assessment of the investigational regimen
• Treatment with alemtuzumab within 6 months before anticipated leukapheresis, or treatment with fludarabine or cladribine within 3 months before anticipated leukapheresis
• Participants with uncontrolled systemic fungal, bacterial, viral, or other infection despite appropriate antibiotics or other treatment at the time of enrollment
• Presence of acute or chronic graft-versus-host disease
• History of any one of the following cardiovascular conditions within the past 6 months: class III or IV heart failure as defined by the New York Heart Association, cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease
• History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
• Pregnant or nursing women. NOTE: Women of reproductive potential must have a negative serum pregnancy test performed within 48 hours before starting conditioning chemotherapy. Pregnant women are excluded from this study because axicabtagene ciloleucel has not been studied in pregnant women. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with axicabtagene ciloleucel, breastfeeding should be discontinued if the mother is treated with axicabtagene ciloleucel. These potential risks may also apply to other agents used in this study
• Use of the following:
• Therapeutic doses of corticosteroids (defined as \> 20 mg/day prednisone or equivalent) within 7 days before leukapheresis or 72 hours before axicabtagene ciloleucel administration. Physiologic replacement, topical, and inhaled steroids are permitted
• Chemotherapy given after leukapheresis to maintain disease control must be stopped \>= 7 days before conditioning chemotherapy
• Cytotoxic chemotherapeutic agents that are not considered lymphotoxic (see below) within 1 week before leukapheresis. Oral chemotherapeutic agents, including lenalidomide and ibrutinib, are allowed if at least 3 half-lives have elapsed prior to leukapheresis
• Lymphotoxic chemotherapeutic agents (e.g., cyclophosphamide, ifosfamide, bendamustine) within 2 weeks before leukapheresis
• Experimental agents received within 4 weeks before leukapheresis unless no response or disease progression is documented while on the experimental therapy and at least 3 half-lives have elapsed before leukapheresis

Sponsors & Collaborators

• AIDS Malignancy Consortium: lead
• National Cancer Institute (NCI): collaborator
• Memorial Sloan Kettering Cancer Center: collaborator

Study Sites (6)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

RECRUITING

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

The Ohio state University

Columbus, Ohio, 43210, United States

RECRUITING

University of Pennsylvania / Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

MeSH Terms

Conditions

HIV Infections; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin

Interventions

axicabtagene ciloleucel; Cyclophosphamide; fludarabine

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, B-Cell; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Ariela Noy

  AIDS Malignancy Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ariela Noy

CONTACT

646-608-3727; noya@mskcc.org

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: October 1, 2021
• First Posted: October 14, 2021
• Study Start: February 13, 2025
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): January 31, 2029
• Last Updated: April 14, 2026

Record last verified: 2026-04

Locations

US (6)