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

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the treatment Fecal Microbiota Transplantation for Lymphoma?

Research shows that CAR T-cell therapies like Tisagenlecleucel (Kymriah) and Axicabtagene ciloleucel (Yescarta) are effective in treating certain types of relapsed or refractory B-cell lymphomas, including diffuse large B-cell lymphoma. These therapies have been approved by regulatory authorities and have shown positive outcomes in clinical trials. ^{1 2 3 4 5}

Is CAR-T cell therapy generally safe for humans?

CAR-T cell therapy, used for treating certain types of lymphoma, has shown potential side effects like cytokine release syndrome (a severe immune reaction) and neurotoxicity (nerve damage). These side effects are important considerations, but strategies are being developed to manage them effectively. ^{1 6 7 8 9}

How is fecal microbiota transplantation for lymphoma different from other treatments?

Fecal microbiota transplantation (FMT) is unique because it involves transferring healthy gut bacteria to patients, potentially improving their response to treatments like CAR-T therapy by altering the gut microbiome, which is not a focus of traditional chemotherapy or CAR-T cell therapy alone. ^{10 11 12 13 14}

Research Team

Neeraj Saini, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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 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 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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

CAR T Cell Toxicity: Current Management and Future Directions. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Outcomes of Tisagenlecleucel in Lymphoma Patients With Predominant Management in an Ambulatory Setting. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Tisagenlecleucel CAR T-cell therapy in secondary CNS lymphoma. [2022]

5. France 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. [2021]

6. Italy 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). [2022]

7. United States 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. [2022]

8. England pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy for B-cell lymphomas: clinical trial results of available products. [2020]

9. Switzerland 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. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Microbiome alteration via fecal microbiota transplantation is effective for refractory immune checkpoint inhibitor-induced colitis. [2023]

11. Switzerland 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. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation for Immune Checkpoint Inhibitor-Induced Colitis Is Safe and Contributes to Recovery: Two Case Reports. [2023]

13. England pubmed.ncbi.nlm.nih.gov

Future indications and clinical management for fecal microbiota transplantation (FMT) in immuno-oncology. [2023]

14. England 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). [2023]