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

To find out if adding treatment with fecal microbiota transplantation (FMT) is effective at treating gut-related side effects of antibiotic treatment in participants who are receiving standard therapy with anti-CD19 chimeric antigen receptor T-cell (CAR-T cell) therapy.

Study Overview

• Status: Recruiting
• Conditions: Lymphoma
• Intervention / Treatment: Drug: Fecal Microbiota Transplantation; Procedure: Chemotherapy; Procedure: CAR-T Therapy

Detailed Description

Primary Objectives

1. To assess the toxicity of combination of FMT with anti-CD19 Axicabtagene ciloleucel therapy and compare it with standard of care Arm B with anti-CD19 CAR-T arm
2. To assess the response in participants treated with the combination of FMT and Axicabtagene ciloleucel CAR T-cell therapy at day 30 and compare it with standard of care Arm B with anti-CD19 CAR-T arm.

Secondary Objectives

1. To assess PFS and OS among participants with and without FMT.
2. To assess changes in gut microbiome of lymphoma participants after FMT.
3. To assess dynamic changes in serum and stool metabolites after FMT.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Neeraj Saini, MD; Phone Number: (713) 792-4504; Email: nsaini@mdanderson.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
      • Contact: Neeraj Saini, MD; Phone Number: 713-792-4504; Email: nsaini@mdanderson.org
      • Principal Investigator: Neeraj Saini, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Will receive FMT therapy (both as a colonoscopy / FMT procedure and as capsules taken by mouth) plus the scheduled chemotherapy and CAR-T cell therapy.	Drug: Fecal Microbiota Transplantation; Given by PO; Procedure: Chemotherapy; Given by Infusion; Procedure: CAR-T Therapy; Given by Infusion
Experimental: Arm B; Will receive no FMT therapy and only receive their scheduled chemotherapy and CAR-T cell therapy.	Procedure: Chemotherapy; Given by Infusion; Procedure: CAR-T Therapy; Given by Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and adverse events (AEs)	Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0	Through study completion; an average of 1 year.

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Investigators: Principal Investigator: Neeraj Saini, MD, M.D. Anderson Cancer Center

Publications and helpful links

General Publications

• Prasad R, Rehman A, Rehman L, Darbaniyan F, Blumenberg V, Schubert ML, Mor U, Zamir E, Schmidt S, Hayase T, Chang CC, McDaniel L, Flores I, Strati P, Nair R, Chihara D, Fayad LE, Ahmed S, Iyer SP, Wang M, Jain P, Nastoupil LJ, Westin J, Arora R, Turner J, Khawaja F, Wu R, Dennison JB, Menges M, Hidalgo-Vargas M, Reid K, Davila ML, Dreger P, Korell F, Schmitt A, Tanner MR, Champlin RE, Flowers CR, Shpall EJ, Hanash S, Neelapu SS, Schmitt M, Subklewe M, Francois-Fahrmann J, Stein-Thoeringer CK, Elinav E, Jain MD, Hayase E, Jenq RR, Saini NY. Antibiotic-induced loss of gut microbiome metabolic output correlates with clinical responses to CAR T-cell therapy. Blood. 2025 Feb 20;145(8):823-839. doi: 10.1182/blood.2024025366.

Helpful Links

• MD Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: January 11, 2024
• First Submitted That Met QC Criteria: January 11, 2024
• First Posted (Actual): January 23, 2024

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hemic and Lymphatic Diseases; Lymphoma; Investigative Techniques; Therapeutics; Biological Therapy; Immunologic Techniques; Immunomodulation; Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Drug Therapy; Fecal Microbiota Transplantation; Immunotherapy, Adoptive
• Other Study ID Numbers: 2023-0581; NCI-2024-00282 (Other Identifier: NCI-CTRP Clinical Registry)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No