Restoring gut bacteria before stem cell transplant for blood cancer patients

Intestinal Microbiota Transplant Prior to Allogeneic Stem Cell Transplant (MAST) Trial

This study is testing if restoring gut bacteria with a special treatment before stem cell transplants can help blood cancer patients have better health and treatment outcomes.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Imperial College London (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 8 sites (Birmingham, England and 7 other locations)
• Trial ID: NCT06355583 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of intestinal microbiota transplantation (IMT) in restoring gut microbiota to healthier levels in patients with various blood cancers who are scheduled for stem cell transplants. Participants will receive either IMT or a placebo two weeks prior to their transplant and will be monitored for changes in gut microbiome diversity, health markers, and outcomes related to their cancer treatment. The study will assess tolerability and acceptability through patient questionnaires and will collect stool, urine, and blood samples at routine follow-up visits.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and over with specific types of blood cancers who are fit for allogeneic hematopoietic cell transplantation.

Not a fit: Patients with severe comorbidities or those not scheduled for stem cell transplants may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve health outcomes and reduce complications for patients undergoing stem cell transplants for blood cancers.

How similar studies have performed: While the concept of microbiota transplantation is gaining interest, this specific approach is relatively novel and has not been extensively tested in the context of stem cell transplants for blood cancers.

Eligibility criteria

Inclusion Criteria:

1. \- Patients aged 18 years and over with a morphological documented diagnosis of ALL, acute myeloid leukemia (AML), AL of ambiguous lineage, myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), and CML in blast phase (Appendix 2) who are deemed fit for allogenic HCT with one of the following disease characteristics: ALL, AML, AL of ambiguous lineage

   * Patients in first complete remission (CR1) or second complete remission (CR2) including complete remission with incomplete blood count recovery with \< 5% blasts (Appendix 2)
   * Secondary leukaemia (defined as previous history of MDS, antecedent haematological disease or chemotherapy exposure) in CR1 or CR2 defined as \< 5% blasts (Appendix 2) MDS and CMML
   * Patients with advanced or high risk MDS with an International Prognostic Scoring System (IPSS-M) moderate high or higher including intermediate or high risk CMML who have \< 5% blasts at the time of randomisation (Appendix 2) CML in blast phase
   * Patients with Philadelphia or BCR:ABL1 positive chronic myeloid leukaemia (CML) in blast phase defined by the presence of ≥ 20% blasts in blood or bone marrow who have achieved second chronic phase with \< 5% blasts (Appendix 2).
2. Patients must have completed minimum of two cycles of intensive chemotherapy prior to trial enrolment (Appendix 1)
3. Patients must have received broad-spectrum antibiotics within 3 months prior to trial enrolment
4. Patients must be considered suitable/fit to undergo allogeneic hematopoietic cell transplantation (HCT) as clinically judged by the Local investigator
5. Patients with an Karnofsky performance status score 60 or above (Appendix 3)
6. Females of and male patients of reproductive potential (i.e., not post-menopausal or surgically sterilised) must use appropriate, highly effective, contraception from the point of commencing therapy until 6 months after treatment
7. Patients have given written informed consent
8. Patients willing and able to comply with scheduled study visits and laboratory tests

Exclusion Criteria:

1. Patients with contraindications to receiving allogeneic HCT.
2. Female patients who are pregnant or breastfeeding. All women of childbearing potential must have a negative pregnancy test before commencing treatment.
3. Adults of reproductive potential not willing to use appropriate, highly effective, contraception during the specified period.
4. Patients with renal or hepatic impairment as clinically judged by the Local Investigator.
5. Patients with active infection, HIV-positive or chronic active hepatitis B virus (HBV) or hepatitis C virus (HCV).
6. Patients with a concurrent active malignancy or a prior malignancy, except lobular breast carcinoma in situ, fully resected basal cell or squamous cell carcinoma of skin or treated cervical carcinoma in situ, incidental histologic finding of prostate cancer (T1a or T1b using the tumour, node, metastasis (TNM) clinical staging system), previous MDS, CMML, Myeloproliferative neoplasms (MPN) resulting in secondary AML. Cancer treated with curative intent ≥ 5 years previously will be allowed. Cancer treated with curative intent \< 5 years previously will not be allowed.
7. Swallowing difficulties that may preclude safe use of IMT capsules.
8. Administration of IMT within 3 months prior to enrolment (probiotic administration prior to enrolment is allowed but should be recorded at screening).
9. Patients taking probiotics after enrolment to the trial.
10. Gastrointestinal disorders and diseases, including delayed gastric emptying, coeliac disease, cystic fibrosis, inflammatory bowel disease, irritable bowel syndrome, chronic diarrhoea, and colonic perforation or fistula.
11. Any autoimmune disease requiring, or that may require, systemic treatment with steroids and/or other immunosuppressants/immunomodulators.
12. Significant bleeding disorder (ALL, AML, AL of ambiguous lineage, MDS, CMML, and CML satisfying inclusion criteria are not excluded).
13. Anaphylactic food allergy.
14. Requirement for vasopressors.
15. Valvular heart disease or known structural defects of the heart.
16. Known severe allergy to capsule components.

Where this trial is running

Birmingham, England and 7 other locations

• University Hospitals Birmingham NHS Foundation Trust — Birmingham, England, United Kingdom (Recruiting)
• Leeds Teaching Hospital NHS Trust — Leeds, England, United Kingdom (Not_yet_recruiting)
• University College London Hospitals NHS Trust — London, England, United Kingdom (Recruiting)
• Kings College NHS Foundation Trust — London, England, United Kingdom (Recruiting)
• Imperial College Healthcare NHS Trust — London, England, United Kingdom (Recruiting)
• Royal Mardsen Hostpital — London, United Kingdom (Recruiting)
• Manchester University NHS Foundation Trust — Manchester, United Kingdom (Not_yet_recruiting)
• Manchester University NHS Trust — Manchester, United Kingdom (Recruiting)

Study contacts

• Principal investigator: Jiri Pavlu — Imperial College London
• Study coordinator: Clinical Trials Coordinator

Conditions Acute Lymphoblastic Leukaemia; Acute Leukemia of Ambiguous Lineage; Chronic Myeloid Leukemia; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome; Acute Myeloid Leukemia; MAST