Fecal transplant to restore gut microbiome before CAR T therapy for relapsed or refractory B‑cell lymphoma
A Phase 2 Randomized Trial of Remodeling Intestinal Microbiota Using Fecal Microbiome Transplant (FMT) Among Recipients of Chimeric Antigen Receptor T Cells (CAR T)
This trial will test whether a fecal microbiome transplant can restore healthy gut bacteria and improve outcomes for adults with relapsed or refractory CD19 B‑cell lymphoma who received high‑risk antibiotics and are receiving CAR T‑cell therapy.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 56 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | City of Hope Medical Center Academic / other |
| Drugs / interventions | CAR T, chimeric antigen receptor, chemotherapy |
| Locations | 1 site (Duarte, California) |
| Trial ID | NCT07042438 on ClinicalTrials.gov |
What this trial studies
This Phase II trial enrolls adults with relapsed or refractory CD19 B‑cell lymphomas who had recent exposure to high‑risk broad‑spectrum antibiotics and are scheduled to receive commercial axicabtagene ciloleucel (YESCARTA). Participants receive fecal microbiota transplantation from healthy donors to repopulate protective gut organisms, with samples taken over time to measure microbiome diversity using the Shannon alpha diversity index at day 0 and subsequent timepoints. Key clinical endpoints include complete and overall response rates at 30, 90 days and 1 year, rates of CRS and ICANS, infections, engraftment of donor strains, safety and feasibility, and recovery of neutropenia. Exploratory analyses compare characteristics of manufactured CAR T products between patients who did or did not receive FMT.
Who should consider this trial
Good fit: Adults (≥18) with relapsed or refractory CD19 B‑cell lymphomas who are eligible for commercial YESCARTA, have Karnofsky ≥60, have recovered from acute toxic effects of prior therapy, and had exposure to high‑risk antibiotics within 90 days are the intended candidates.
Not a fit: Patients without recent high‑risk antibiotic exposure, those not receiving CAR T therapy, or those with contraindications to FMT (for example certain uncontrolled infections or severe GI conditions) are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, FMT could increase gut microbial diversity and potentially improve CAR T therapy effectiveness while reducing infectious complications and toxicities.
How similar studies have performed: Early clinical and preclinical work shows the gut microbiome can influence cancer immunotherapy and small FMT trials have modulated responses in other immunotherapy settings, but using FMT specifically to improve CAR T outcomes is a novel and largely untested approach.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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 * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Agreement by females and males of childbearing potential\* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 12 months after the last dose of protocol therapy. * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only) Exclusion Criteria: * 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)
Where this trial is running
Duarte, California
- City of Hope Medical Center — Duarte, California, United States (Recruiting)
Study contacts
- Principal investigator: Karamjeet S Sandhu — City of Hope Medical Center
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.