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Fecal Microbiome Transplant to Remodel Intestinal Microbiota for Patients With Relapsed or Refractory Lymphoma With Exposure to High-Risk Antibiotics Who Are Receiving Chimeric Antigen Receptor T Cells

ConditionsRecurrent Diffuse Large B-Cell LymphomaRecurrent High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 RearrangementsRecurrent Transformed Follicular Lymphoma to Diffuse Large B-Cell LymphomaRefractory Diffuse Large B-Cell LymphomaRefractory High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 RearrangementsRefractory Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorCity of Hope Medical Center

About this trial

This phase II trial tests how well fecal microbiome transplantation works to remodel intestinal microbiota for patients with lymphoma that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory) with exposure to high-risk antibiotics who are receiving chimeric antigen receptor (CAR) T cells. Fecal microbiome transplantation consists of fecal microbiota from healthy donors with healthy gut microbiota that allows re-population of the patient's microbiome with diverse protective microorganisms. CAR T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Part of the treatment for CAR T therapy involves high doses of chemotherapy. This, along with prior exposure to high strength antibiotics, can damage patient's intestinal microbiota. Giving fecal microbiome transplantation may improve clinical response by repairing intestinal microbiota for patients with relapsed or refractory lymphoma who had exposure to high-risk antibiotics.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • Axicabtagene Ciloleucel

    Biological/Vaccine

    Given CAR-T cells

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Chemotherapy

    Drug

    Receive chemotherapy

  • Fecal Microbiota Transplantation

    Procedure/Surgery

    Given PO

  • Leukapheresis

    Procedure/Surgery

    Undergo leukapheresis

  • Placebo Administration

    Drug

    Given PO

Treatment groups

56 Participants
are divided into 2 treatment groups
Group A: Arm I (FMT)Experimental treatment 5 interventions
Group B: Arm II (Placebo)Placebo comparator 5 interventions

Trial outcomes

Primary outcomes

1

Changes in gut microbiome diversity

Assessed using the Shannon alpha diversity index. For comparisons at a timepoint of most interest, a t-test (or Wilcoxon rank-sum test if assumptions are not met) will be used to compare the Shannon index between the fecal microbiome transplant (FMT) and placebo groups. For over-time comparisons, linear mixed models will be used to assess longitudinal changes in microbiome diversity between treatment (FMT) and control (placebo) groups, accounting for within-subject correlations over multiple measurement points.

Time frame
From baseline to day 0

Secondary outcomes

1

Rate of complete response

Time frame
At day +30, +90 and 1 year after chimeric antigen receptor t cell (CAR T) therapy
2

Incidence of adverse events

Scored using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 scale. Will summarize adverse events by type, severity, attribution, time of onset, duration, and association with study treatment. All observed toxicities will be tabulated and summarized by grade and frequency.

Time frame
Up to 1 year post CAR T cell therapy
3

Feasibility of Rx administration

Evaluated by assessment of patient's ability to take at least 2 of the first 4 doses of Rx (4 capsules of FMT or placebo) before CAR T infusion.

Time frame
Up to 30 days before CAR T cell infusion
4

Quantify engraftment of bacterial strains that are definitely attributable to FMT product

Donor microbiota engraftment will be determined by SourceTracker. SourceTracker estimates the attribution of microbiota in a post-treatment sample to donor microbiota. In choosing the donor source for each post-FMT sample, only the specific donor whose product was administered to the patient was used as donor. By contrast, because placebo capsules did not contain any donor material, the calculated engraftment rates from all four presumptive donors were averaged to derive donor attribution of post-placebo microbiota.

Time frame
Up to 1 year post CAR T cell therapy

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

City of Hope Medical Center

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
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