Fecal Microbiota Transplantation in Patients Undergoing Chimeric Antigen Receptor T-cell Therapy and Allogeneic Stem Cell Transplant: A Pilot Study

Overview

This is a single site pilot trial will evaluate the feasibility and safety of fecal microbiota transplantation (FMT) in patients with B-cell lymphoma who are undergoing CAR-T or in patients with moderate to high-risk acute myeloid leukemia or myelodysplastic syndrome who are undergoing allogeneic stem cell transplantation.

Detailed description

This is a single centre, non-randomized, single-arm interventional pilot study examining fecal microbiota transplantation in patients undergoing CAR-T or allogeneic stem cell transplantation (alloSCT). 20 eligible patients will be enrolled in this study 10 patients with B-cell lymphoma undergoing CAR-T and 10 patients with AML/MDS undergoing alloSCT. FMT series occurring prior to cellular therapy and 30 days after cellular therapy treatment. Standard of care blood tests including HIV, Hepatitis B and C testing, pregnancy test and physical exam will be done during the study. Blood, urine, rectal swab, stool sample will be collected for correlative studies. Patients will be asked to complete a questionnaire questionnaire on perceptions and acceptability of FMT. The total study duration will be approximately 2.5 years, including 2 years of recruitment, minimum 1 series of FMT treatments and a minimum 6 months of follow-up.

Interventions

• Biological Fecal Microbial Transplant Enema
  Rectal infusion of FMT will be administered every 48 hours for 2 doses, on 2 separate occasions, detailed in the study calendar. For each series of FMT administrations, the first dose will be 100g and the second will be 50g. Each FMT will be delivered using a single dose (300 ml of prepared fecal filtrate containing 100g or 50g of stool from a donor) delivered using an enema bag and rectal catheter. The procedure, including preparation steps, will take less than 20 - 30 minutes. The second FMT
• Biological Fecal Microbial Transplant Enema
  Rectal infusion of FMT will be administered every 48 hours for 2 doses, on 2 separate occasions, detailed in the study calendar. For each series of FMT administrations, the first dose will be 100g and the second will be 50g. Each FMT will be delivered using a single dose (300 ml of prepared fecal filtrate containing 100g or 50g of stool from a donor) delivered using an enema bag and rectal catheter. The procedure, including preparation steps, will take less than 20 - 30 minutes. The second FMT

Primary outcome measures

• To evaluate the feasibility of fecal microbiota transplantation (FMT) in patients undergoing CAR-T or allogeneic stem cell transplantation. [Time frame: 2.5 years]
• To evaluate the safety of fecal microbiota transplantation (FMT) in patients undergoing CAR-T or allogeneic stem cell transplantation. [Time frame: 2.5 years]

Eligibility criteria

Inclusion criteria

• Men and women ≥ 18 years of age
• Diagnosis of the following:

• Indolent or aggressive B-cell lymphoma eligible for standard or care CAR-T therapy (Cohort A), or
• Patients with AML or high risk MDS with indication to undergo reduced-intensity conditioning alloSCT, with an available matched related, unrelated, or haploidentical donor (Cohort B)
• ECOG 0-1
• Adequate marrow function defined by:

• Hemoglobin >80 g/L without transfusion dependence within the last 7 days
• Platelet count >20 x 109/L without transfusion dependence within the last 7 days
• Neutrophil count >1.0 x 109/L without growth factor support within the last 7 days
• Adequate liver function as indicated by aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x the institutional upper limits of normal (ULNs) value; serum total bilirubin < 1.5 x ULN (unless documented Gilbert's syndrome)
• Adequate renal function as defined as creatinine clearance ≥ 30 mL/min directly measured with a 24-hour urine collection or calculated according to the modified formula of Cockcroft-Gault equation or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) calculation
• Life expectancy >6 months
• Women of childbearing potential (WOCBP) who are sexually active must use highly effective methods of contraception during treatment and up to 6 months after the last dose of protocol therapy. Men who are sexually active must use highly effective methods of contraception during treatment and up to 6 months after the last dose of protocol therapy. Men require an agreement to remain abstinent (ie, refrain from heterosexual intercourse) or use a condom, and an agreement to refrain from donating sperm. Periodic abstinence and withdrawal are not acceptable methods of contraception. Fertility preservation options should be discussed. Examples of highly effective contraceptive methods include an agreement to remain abstinent (ie, refrain from heterosexual intercourse), bilateral tubal ligation, male sterilization, established proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
• Willing and able to participate in all required evaluations and procedures in this study.
• Ability to understand and the willingness to sign a written informed consent.

Exclusion criteria

• For patients undergoing alloSCT (Cohort B): plan to undergo myeloablative conditioning
• Use of investigational agents within the last 4 weeks before enrollment.
• Active or uncontrolled infection
• Autoimmune disorder currently being treated with disease-modifying therapy or with >10mg/day prednisone
• Inflammatory bowel disease
• History of intestinal perforation
• Gastrointestinal surgical procedure within the past 4 weeks before enrollment
• Pregnant or breast-feeding patients
• HIV infection with detectable viral load or CD4 count <200
• Serologic status reflecting active hepatitis B or C infection as follows:

• Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with detectable hepatitis B virus (HBV) DNA. (Note, patients with undetectable HBV DNA are permitted to enroll if they are on Hepatitis B suppressive therapy)
• Patients with presence of hepatitis C virus (HCV) antibody and HCV RNA detectable
• History of infection or known colonization with antibiotic resistant organism in the last two years before enrollment (including ESBL, MRSA, VISA, VRSA, VRE, CPE)
• Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in the study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Canada · 1 center

• University Health Network — Toronto

Identifiers

NCT: NCT07509450 · FMT Pilot Study · OZUHN-038

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗