Fecal Microbiota Transplantation for Lymphoma

Overseen By Neeraj Saini, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Broad-spectrum antibiotics

Must not be taking: Live vaccines

Disqualifiers: Surgery, Immunodeficiency, Pregnancy, IBD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 4-6 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding fecal microbiota transplantation (FMT) can help manage gut problems caused by antibiotics in people receiving CAR-T cell therapy for B-cell lymphomas. Participants will receive either standard chemotherapy and CAR-T therapy or the same treatments plus FMT, which involves transferring healthy gut bacteria. This trial may suit people with B-cell lymphomas who have recently taken strong antibiotics. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in managing gut health during cancer treatment.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss your specific medications with the trial team to get a clear answer.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that fecal microbiota transplantation (FMT) is generally safe for patients. It effectively treats gut infections like Clostridium difficile, with success rates between 80% and 90%. In cancer treatment, FMT has been used safely to manage side effects and improve outcomes. For people with B-cell lymphoma, FMT might help with gut-related side effects. Another study found that FMT safely prevents complications like graft-versus-host disease in patients undergoing treatment. Overall, FMT is considered a safe and promising treatment in these situations. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Fecal Microbiota Transplantation (FMT) for lymphoma because it offers a novel way to enhance the effectiveness of existing treatments like chemotherapy and CAR-T therapy. Unlike traditional treatments that focus directly on attacking cancer cells, FMT aims to improve the gut microbiome, potentially boosting the immune response and reducing treatment-related side effects. This approach is unique as it involves an innovative delivery method, using both colonoscopy and oral capsules, to introduce healthy bacteria into the patient's system. By improving gut health, FMT may enhance the body's overall ability to fight lymphoma, offering a promising new avenue in cancer treatment.

What evidence suggests that fecal microbiota transplantation could be effective for treating gut-related side effects in lymphoma patients?

Research shows that Fecal Microbiota Transplantation (FMT) effectively treats recurrent Clostridium difficile infections, with success rates between 80% and 90%. Studies on FMT for cancer patients are promising, as it may improve treatment outcomes and reduce side effects. In this trial, participants in Arm A will receive FMT therapy, both as a colonoscopy/FMT procedure and as capsules taken orally, alongside their scheduled chemotherapy and CAR-T cell therapy. This approach might help manage gut issues when combined with treatments like CAR-T cell therapy. Some research suggests that oral FMT could be more effective than other methods. Early evidence indicates that FMT could be a valuable addition to cancer treatment plans, particularly for gut health. Participants in Arm B will receive only their scheduled chemotherapy and CAR-T cell therapy without FMT. ^{1 2 3 4 5}

Who Is on the Research Team?

Neeraj Saini, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for lymphoma patients who are undergoing CAR-T cell therapy and experiencing gut-related side effects from antibiotics. It's designed to see if fecal microbiota transplantation (FMT) can help with these issues.

Inclusion Criteria

The participant (or legally acceptable representative if applicable) provides written informed consent for the trial

My liver is functioning within the required limits.

I have been treated with strong antibiotics recently.

Exclusion Criteria

For women of childbearing age, a positive urine pregnancy test within 72 hours prior to enrollment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

I have been diagnosed with a primary immunodeficiency, but not IgA deficiency.

I do not have a history of irritable or inflammatory bowel disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive FMT therapy and CAR-T cell therapy, or only CAR-T cell therapy

4-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• CAR-T Therapy
• Chemotherapy
• Fecal Microbiota Transplantation

Trial Overview The study is testing whether adding FMT to standard anti-CD19 CAR-T cell therapy can reduce gastrointestinal complications in lymphoma patients. This pilot trial will provide initial data on the effectiveness of this combination treatment.

How Is the Trial Designed?

Group I: Arm B Experimental Treatment 2 Interventions

Will receive no FMT therapy and only receive their scheduled chemotherapy and CAR-T cell therapy.

Group II: Arm A Experimental Treatment 3 Interventions

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.

CAR-T Therapy is already approved in United States, European Union for the following indications:

Approved in United States as Kymriah for:

• B-cell precursor acute lymphoblastic leukemia (ALL)
• Relapsed or refractory large B-cell lymphoma
• Diffuse large B-cell lymphoma (DLBCL)

Approved in European Union as Kymriah for:

• B-cell precursor acute lymphoblastic leukemia (ALL)
• Relapsed or refractory large B-cell lymphoma
• Diffuse large B-cell lymphoma (DLBCL)

Approved in United States as Yescarta for:

• Relapsed or refractory large B-cell lymphoma
• Diffuse large B-cell lymphoma (DLBCL)

Approved in European Union as Yescarta for:

• Relapsed or refractory large B-cell lymphoma
• Diffuse large B-cell lymphoma (DLBCL)

Approved in United States as Tecartus for:

• Relapsed or refractory mantle cell lymphoma
• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL)

Approved in European Union as Tecartus for:

• Relapsed or refractory mantle cell lymphoma
• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL)

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

Two CAR T cell therapies, Tisagenlecleucel and Axicabtagene ciloleucel, have been approved for treating specific types of blood cancers, including B-cell acute lymphoblastic leukemia and large B-cell lymphoma, in patients who have not responded to other treatments.

This review emphasizes the importance of recognizing and managing the toxicities associated with CAR T cell therapies, while also suggesting future strategies to reduce these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cell Toxicity: Current Management and Future Directions. Yáñez, L., Sánchez-Escamilla, M., Perales, MA.[2020]

CAR T cell therapies, such as tisagenlecleucel and axicabtagene ciloleucel, are effective treatments for certain types of blood cancers, specifically targeting the CD19 antigen in patients with relapsed or refractory conditions.

The recommendations provided by the European Society of Blood and Marrow Transplantation cover comprehensive patient care aspects, including eligibility, treatment procedures, and management of potential complications, ensuring a structured approach to administering these innovative therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of adults and children undergoing chimeric antigen receptor T-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE). Yakoub-Agha, I., Chabannon, C., Bader, P., et al.[2022]

CAR-T cell therapies, specifically axicabtagene ciloleucel and tisagenlecleucel, have significantly improved outcomes for patients with relapsed or refractory aggressive B-cell lymphomas, with approvals based on pivotal trials demonstrating their efficacy after multiple prior treatments.

Despite their similar CAR technologies, differences in manufacturing and clinical trial designs exist between these therapies, highlighting the need for ongoing monitoring of patient responses and potential long-term side effects in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of CD19-directed CAR-T cell therapies in patients with relapsed/refractory aggressive B-cell lymphomas: Observations from the JULIET, ZUMA-1, and TRANSCEND trials. Westin, JR., Kersten, MJ., Salles, G., et al.[2022]

The composition of gut microbiota can influence tumor growth and the effectiveness of immunotherapies, such as CAR T-cell therapy, highlighting its role as an independent organ in cancer treatment.

Probiotics containing Bifidobacterium spp. can enhance the efficacy of PD-1 and CTLA-4 therapies, while certain bacterial groups may help prevent side effects like colitis, indicating that microbiota manipulation could optimize immunotherapy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Frontiers about the Role of Human Microbiota in Immunotherapy: The Immune Checkpoint Inhibitors and CAR T-Cell Therapy Era. Innao, V., Allegra, AG., Musolino, C., et al.[2021]

In a case series of 12 patients with severe immune-mediated colitis (IMC) caused by immune checkpoint inhibitors, 83% experienced symptom improvement after fecal microbiota transplantation (FMT), and 92% achieved clinical remission by the end of the study.

Analysis of stool samples indicated that successful FMT responses were linked to specific microbial changes, including increased diversity and the presence of beneficial bacteria like Collinsella and Bifidobacterium, suggesting that gut microbiota composition plays a crucial role in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microbiome alteration via fecal microbiota transplantation is effective for refractory immune checkpoint inhibitor-induced colitis. Halsey, TM., Thomas, AS., Hayase, T., et al.[2023]

The gut microbiota plays a significant role in cancer treatment, particularly in enhancing the effectiveness of immune checkpoint inhibitors (ICIs), as shown by metagenomic profiling and murine studies.

Fecal microbiota transplantation (FMT) shows promise as a novel therapeutic strategy when combined with ICIs, although safety concerns and challenges related to pathogen transmission need to be addressed before it can be widely adopted in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future indications and clinical management for fecal microbiota transplantation (FMT) in immuno-oncology. Jamal, R., Messaoudene, M., de Figuieredo, M., et al.[2023]

In a phase II trial involving 20 patients with refractory microsatellite stable metastatic colorectal cancer, the combination of fecal microbiota transplantation (FMT) with tislelizumab and fruquintinib resulted in a median progression-free survival of 9.6 months and a median overall survival of 13.7 months, indicating improved efficacy compared to previous treatments.

The treatment was generally safe, with 95% of patients experiencing at least one treatment-related adverse event, but no treatment-related deaths occurred, suggesting that this combination therapy could be a valuable option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation plus tislelizumab and fruquintinib in refractory microsatellite stable metastatic colorectal cancer: an open-label, single-arm, phase II trial (RENMIN-215). Zhao, W., Lei, J., Ke, S., et al.[2023]

CAR T-cell therapy, particularly with anti-CD19 targeting, has shown significant effectiveness in treating aggressive B-cell non-Hodgkin's lymphoma (NHL), leading to long-term remissions in patients with diffuse large B-cell lymphoma (DLBCL) who have not responded to other treatments.

Two CAR T-cell products, axicabtagene ciloleucel and tisagenlecleucel, have been approved by the FDA for refractory DLBCL, while a third product, liso-cel, is showing promising results in ongoing trials, although potential side effects like cytokine-release syndrome and neurotoxicity are important considerations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy for B-cell lymphomas: clinical trial results of available products. Chavez, JC., Bachmeier, C., Kharfan-Dabaja, MA.[2020]

In a pivotal phase 2 study involving 93 adult patients with relapsed or refractory diffuse large B-cell lymphoma, CAR T-cell therapy with tisagenlecleucel achieved a best overall response rate of 52%, with 40% of patients experiencing complete responses.

The treatment demonstrated durable responses, with a 12-month relapse-free survival rate of 65%, and no deaths were attributed to the therapy itself, although some patients experienced significant adverse events like cytokine release syndrome and infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Schuster, SJ., Bishop, MR., Tam, CS., et al.[2019]

In a study of 72 adult patients with relapsed or refractory non-Hodgkin lymphoma treated with tisagenlecleucel, 94.4% received the therapy in an outpatient setting, demonstrating that this approach is both safe and feasible.

The overall response rate was 43%, with a complete response in 34.7% of patients, and serious adverse events like grade 3-4 cytokine release syndrome were not observed, indicating a manageable safety profile for outpatient CAR T therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Tisagenlecleucel in Lymphoma Patients With Predominant Management in an Ambulatory Setting. Nasta, SD., Hughes, ME., Namoglu, EC., et al.[2022]

A survey of 41 experienced clinicians revealed that many do not consider a history of malignancy or prior treatments as contraindications for CAR T-cell therapy, indicating a broader eligibility for patients than previously thought.

There is significant variability in follow-up care models after CAR T therapy, with most clinicians recommending frequent hospital visits in the initial month, highlighting the need for standardized guidelines in patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An international survey on the management of patients receiving CAR T-cell therapy for haematological malignancies on behalf of the Chronic Malignancies Working Party of EBMT. Hayden, PJ., Sirait, T., Koster, L., et al.[2021]

The three CAR-T cell therapies (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) show promising efficacy in treating large B cell lymphoma, with overall response rates of nearly 70% and complete response rates exceeding 50% across 33 studies involving 2,172 patients.

However, axicabtagene ciloleucel and tisagenlecleucel are associated with significant risks of severe neurotoxicity and life-threatening cytokine release syndrome, necessitating careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of CAR-T Cell Products Axicabtagene Ciloleucel, Tisagenlecleucel, and Lisocabtagene Maraleucel for the Treatment of Hematologic Malignancies: A Systematic Review and Meta-Analysis. Meng, J., Wu, X., Sun, Z., et al.[2022]

In a study of 8 patients with secondary CNS lymphoma treated with CAR T cells targeting CD19, no patients experienced severe neurotoxicity, indicating a favorable safety profile for this therapy in this specific population.

Despite the exclusion of CNS involvement in earlier trials, the CAR T cells showed signs of expansion and activity within the CNS, suggesting potential efficacy for treating CNS lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tisagenlecleucel CAR T-cell therapy in secondary CNS lymphoma. Frigault, MJ., Dietrich, J., Martinez-Lage, M., et al.[2022]

Fecal microbiota transplantation (FMT) improved symptoms of immune-mediated enterocolitis (IMC) in two patients with metastatic cancer, leading to increased defecation frequency and reduced need for immunosuppressive therapy after treatment.

Both patients showed significant changes in their gut microbiota composition post-FMT, with diversity levels returning to those similar to healthy donors, suggesting that microbiome modulation could be a promising therapeutic approach for managing IMC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation for Immune Checkpoint Inhibitor-Induced Colitis Is Safe and Contributes to Recovery: Two Case Reports. Groenewegen, B., Terveer, EM., Joosse, A., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6139215/

A Systematic Review of the Efficacy and Safety of Fecal ... Fecal microbiota transplantation (FMT) has been shown to be effective in recurrent Clostridium difficile (CD) infection, with resolution in 80% to 90% of ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0305737225001471

Fecal microbiota transplantation to enhance cancer ... This systematic review evaluates Fecal Microbiota Transplantation (FMT)'s impact on cancer treatment outcomes and treatment-related toxicity and explores its ...

3. bmcmedicine.biomedcentral.com bmcmedicine.biomedcentral.com/articles/10.1186/s12916-025-04183-y

Microbiota boost immunotherapy? A meta-analysis dives into ... As for FMT methods, oral fecal microbiota capsules appeared to be more effective (ORR: 49%) compared to endoscopic delivery (ORR: 34%) or ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-00282

Fecal Microbiota Transplantation for Reducing Gut-Related ... Fecal Microbiota Transplantation for Reducing Gut-Related Side Effects and Improving Treatment Outcomes in Patients with B-Cell Lymphoma Receiving CAR T-cell ...

5. fredhutch.org fredhutch.org/en/news/releases/2025/01/fecal-microbiota-transplantation-after-stem-cell-transplantation.html

Could fecal microbiota transplantation help patients heal ... A new study shows that oral fecal microbiota transplantation (FMT) is a feasible and safe addition to preventing graft-versus-host disease in patients ...