Using fecal microbiota transplantation to improve treatment for lymphoma patients receiving CAR-T therapy

Pilot Trial of Fecal Microbiota Transplantation for Lymphoma Patients Receiving Axicabtagene Ciloleucel Therapy.

This study is testing if a stool transplant can help lymphoma patients feel better and have fewer side effects while receiving a special cancer treatment called CAR-T therapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: M.D. Anderson Cancer Center (Academic / other)
• Drugs / interventions: CAR-T, chimeric antigen receptor, CAR T
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT06218602 on ClinicalTrials.gov

What this trial studies

This pilot trial investigates the effectiveness of fecal microbiota transplantation (FMT) in alleviating gut-related side effects in lymphoma patients undergoing anti-CD19 chimeric antigen receptor T-cell therapy with Axicabtagene ciloleucel. The study aims to compare the toxicity and treatment response of patients receiving FMT alongside CAR-T therapy against those receiving standard care. Additionally, it will evaluate progression-free survival (PFS) and overall survival (OS) rates, as well as changes in the gut microbiome and metabolites following FMT. The trial is designed to provide insights into the potential benefits of FMT in this patient population.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with confirmed B-cell lymphomas who are scheduled to receive Axicabtagene ciloleucel therapy and have recently been treated with high-risk broad-spectrum antibiotics.

Not a fit: Patients who do not have B-cell lymphomas or are not receiving CAR-T therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce gut-related side effects and improve treatment outcomes for lymphoma patients receiving CAR-T therapy.

How similar studies have performed: While the use of FMT in cancer treatment is emerging, this specific combination with CAR-T therapy is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

1. At least 18 years of age on the day of signing informed consent.
2. Histologically/cytologically confirmed diagnosis of B-cell lymphomas.
3. Is being planned to received FDA approved standard of care anti-CD19 Axicabtagene Ciloleucel.
4. Participants must have received or is receiving high-risk broad-spectrum antibiotics for minimum of two days within 180 days of scheduled Axicabtagene ciloleucel infusion. 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.
5. An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Evaluation of ECOG is to be performed within 7 days prior to the date of signing study consent.
6. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
7. Absolute neutrophil counts should be greater than 1000/ul at the time of administration of fecal enema.
8. Adequate hepatic function defined by a total bilirubin level ≤ 1.5 ≤ x the upper limit of normal (ULN)\[except if Gilberts syndrome and then total bilirubin ≤ 3x is allowed\], an AST, level ≤ 2.5 x ULN, and an ALT level ≤ 2.5 x ULN. If liver metastases are present, then AST and ALT levels must be ≤ 4 x ULN
9. Adequate renal function defined by an estimated creatinine clearance \>30 mL/min according to the Cockcroft-Gault formula or by a creatinine clearance measurement from a 24-hour urine collection.
10. Highly effective contraception for both male and female subjects if the risk of conception exists. Highly effective contraception must be used 30 days prior to first study-drug administration, for the duration of trial treatment, and for at least for 12 months after treatment for females and 4 months after treatment for males. Should a female patient (or male participant's sexual partner) become pregnant or should either the female patient (or male participant's partner) suspect she is pregnant while the participant's study-participation is ongoing, the treating physician should be informed immediately.

Exclusion Criteria:

1. If participant received major surgery within last 4 weeks, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
2. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
3. Has a diagnosis of primary immunodeficiency (excluding IgA deficiency).
4. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the study subject's best interest to participate, in the opinion of the treating investigator.
5. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
6. Pregnant or nursing women
7. For women of childbearing age, a serum pregnancy test will be required within 72 hours prior to enrollment. If the serum test is positive, patient will not be allowed to enroll in the trial.
8. Participants with history of irritable bowel disease and inflammatory bowel disease will be excluded from clinical trial.
9. Participants with difficulties in oral administration or at risk of aspiration (e.g., neurological issues)

Where this trial is running

Houston, Texas

• MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Neeraj Saini, MD — M.D. Anderson Cancer Center
• Study coordinator: Neeraj Saini, MD

Conditions Lymphoma