Fecal Microbiome Transplant to Remodel Intestinal Microbiota for Patients With Relapsed or Refractory Lymphoma With Exposure to High-Risk Antibiotics Who Are Receiving Chimeric Antigen Receptor T Cells

NCT07042438 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 24910NCI-2025-03771P30CA033572
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests how well fecal microbiome transplantation works to remodel intestinal microbiota for patients with lymphoma that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory) with exposure to high-risk antibiotics who are receiving chimeric antigen receptor (CAR) T cells. Fecal microbiome transplantation consists of fecal microbiota from healthy donors with healthy gut microbiota that allows re-population of the patient's microbiome with diverse protective microorganisms. CAR T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Part of the treatment for CAR T therapy involves high doses of chemotherapy. This, along with prior exposure to high strength antibiotics, can damage patient's intestinal microbiota. Giving fecal microbiome transplantation may improve clinical response by repairing intestinal microbiota for patients with relapsed or refractory lymphoma who had exposure to high-risk antibiotics.

Conditions

Recurrent Diffuse Large B-Cell Lymphoma; Recurrent High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements; Recurrent Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements; Refractory Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Changes in gut microbiome diversity

  Assessed using the Shannon alpha diversity index. For comparisons at a timepoint of most interest, a t-test (or Wilcoxon rank-sum test if assumptions are not met) will be used to compare the Shannon index between the fecal microbiome transplant (FMT) and placebo groups. For over-time comparisons, linear mixed models will be used to assess longitudinal changes in microbiome diversity between treatment (FMT) and control (placebo) groups, accounting for within-subject correlations over multiple measurement points.

  From baseline to day 0

Secondary Outcomes (11)

• Rate of complete response

  At day +30, +90 and 1 year after chimeric antigen receptor t cell (CAR T) therapy

• Incidence of adverse events

  Up to 1 year post CAR T cell therapy

• Feasibility of Rx administration

  Up to 30 days before CAR T cell infusion

• Quantify engraftment of bacterial strains that are definitely attributable to FMT product

  Up to 1 year post CAR T cell therapy

• Incidence and severity of Cytokine Release Syndrome

  Up to 1 year post CAR T cell therapy

Study Arms (2)

Arm I (FMT)

EXPERIMENTAL

Patients undergo standard of care leukapheresis and receive standard of care chemotherapy and CAR T cells. Patients receive FMT PO QD on day -10 and -7 before leukapheresis, day -10 and -7 before CAR T cell infusion, within 3 days of neutrophil recovery and 2 days after first neutrophil recovery dose. Treatment given in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study.

Biological: Axicabtagene Ciloleucel; Procedure: Biospecimen Collection; Drug: Chemotherapy; Procedure: Fecal Microbiota Transplantation; Procedure: Leukapheresis

Arm II (Placebo)

PLACEBO COMPARATOR

Patients undergo standard of care leukapheresis and receive standard of care chemotherapy and CAR T cells. Patients receive placebo PO QD on day -10 and -7 before leukapheresis, day -10 and -7 before CAR T cell infusion, within 3 days of neutrophil recovery and 2 days after first neutrophil recovery dose. Treatment given in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study.

Procedure: Biospecimen Collection; Drug: Chemotherapy; Procedure: Fecal Microbiota Transplantation; Procedure: Leukapheresis; Drug: Placebo Administration

Interventions

Axicabtagene Ciloleucel BIOLOGICAL

Given CAR-T cells

Also known as: Axi-cel, Axicel, KTE C19, KTE-C19, KTE-C19 CAR, KTEC19, Yescarta

Arm I (FMT)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm I (FMT); Arm II (Placebo)

Chemotherapy DRUG

Receive chemotherapy

Also known as: Chemo, Chemotherapy (NOS), Chemotherapy, Cancer, General

Arm I (FMT); Arm II (Placebo)

Fecal Microbiota Transplantation PROCEDURE

Given PO

Also known as: Fecal Material Transplantation, Fecal Transplantation, FMT, Poo Transplant, Poop Transplant, Stool Transplant

Arm I (FMT); Arm II (Placebo)

Leukapheresis PROCEDURE

Undergo leukapheresis

Also known as: Leukocyte Adsorptive Apheresis, Leukocytopheresis, Therapeutic Leukopheresis, White Blood Cell Reduction Apheresis

Arm I (FMT); Arm II (Placebo)

Placebo Administration DRUG

Given PO

Arm II (Placebo)

Eligibility Criteria

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

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative.
• Assent, when appropriate, will be obtained per institutional guidelines
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• If unavailable, exceptions may be granted with study principal investigator (PI) approval
• Age: ≥ 18 years
• Karnofsky performance status (KPS) ≥ 60
• Confirmed diagnosis of relapsed/refractory CD19 B-cell lymphomas of diffuse large B cell lymphoma (DLBCL), transformed follicular lymphoma (tFL), or double-hit lymphoma (DHL) and scheduled to receive commercial CAR T treatment of YESCARTA ® for their diagnosis
• Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy
• Exposure to high-risk antibiotics within 90 days of consent. High-risk broad-spectrum antibiotics include carbapenems (meropenem, imipenem, doripenem), anti-pseudomonal antibiotics (cefepime, piperacillin-tazobactam, ceftazidime) or anaerobic antibiotics including metronidazole, clindamycin, amoxicillin-sulbactam, and vancomycin
• Clinical laboratory and organ function criteria per standard of care to CAR T patients at City of hope: (To be performed within 30 days prior to leukapheresis)
• Seronegative for HIV antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative)
• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• Meets other institutional and federal requirements for infectious disease titer requirements
• Note: Infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy
• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test

You may not qualify if:

• Major surgery in 4 months preceding enrollment
• No live vaccine in 30 days prior to enrollment
• Inability to swallow capsules or history of disorder with Inability to swallow FMT capsules
• History of inflammatory bowel disorder, irritable bowel disorder
• Severe food allergies
• History of chronic aspiration
• History of behavioral disorders including substance abuse disorders which per discretion of primary investigator will interfere with safe conduct and compliance to study treatment
• History neurocognitive disorder which per discretion of primary investigator will interfere with safe conduct and compliance to study treatment
• Diagnosis of primary immunodeficiency
• Active second malignancy requiring treatment except non-melanoma skin cancer or carcinoma in situ-cervix, bladder or to non-metastatic prostate cancer which does not require treatment
• Uncontrolled bacterial, fungal, or viral infection confirmed using clinical, laboratory and radiological findings requiring administration of intravenously (IV) antimicrobials
• Any clinical, laboratory or radiologic findings per discretion of primary investigator will interfere with safe conduct of study treatment and compliance with study procedures
• Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

axicabtagene ciloleucel; Specimen Handling; Drug Therapy; Fecal Microbiota Transplantation; Leukapheresis

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Therapeutics; Biological Therapy; Cytapheresis; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques

Study Officials

• Karamjeet S Sandhu

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This single center, double-blind, phase 2a clinical trial
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2025
• First Posted: June 29, 2025
• Study Start: February 11, 2026
• Primary Completion (Estimated): January 23, 2029
• Study Completion (Estimated): January 23, 2029
• Last Updated: March 5, 2026

Record last verified: 2026-03

Locations

US (1)