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

Imperial College London

Status and phase: Enrolling; Phase 2

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

Treatments: Drug: Placebo; Drug: EBX-102

Study type: Interventional

Funder types: Other

Identifiers

NCT06355583

C/42/2022

2022-003617-10 (EudraCT Number)

Details and patient eligibility

About

The goal of this clinical trial is to test the ability to restore gut microbiota to healthier levels in patients with blood cancers scheduled to have stem cell transplant.

The main questions it aims to answer are:

• Tolerability and acceptability of intestinal microbiota transplantation (IMT) versus placebo (as assessed via patient perspective questionnaires
• Changes in gut microbiome diversity across all timepoints
• Markers of general health, infective/microbiological and haematological outcomes including, days of fever, admission to intensive care unit, survival, non-relapsed mortality, and incidence of graft-versus-host disease across all time points measured.

Participants will be asked at their routine follow up visits to,

• Provide stool, urine and blood samples at the scheduled study visits
• Complete questionnaires at selected visits
• Swallow either Placebo or IMT capsules once at the second study visit which will occur 2 weeks prior to the stem cell transplant (+/-3 days)

Researchers will compare IMT capsules and Placebo to investigate the change in gut microbiota diversity.

Enrollment: 50 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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50 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Patients randomised on to the placebo arm will swallow 10 placebo capsules once at the second study visit approximately 2 weeks before the stem cell transplantation. The capsules contain inactive ingredients (microcrystalline cellulose and magnesium stearate) and will have the same appearance, weight, and packaging weight to the IMT capsules in the treatment arm to maintain treatment blinding.

Treatment:

Drug: Placebo

EBX-102-02

Active Comparator group

Description:

Patients randomised on to the Treatment arm will swallow 10 capsules once at the second study visit approximately 2 weeks before the stem cell transplantation. Each capsule will contain 1x10\^6 - 1x10\^9 colony forming units (CFU)/g of viable microorganisms and will have the same appearance, weight and packaging weight to the placebo capsules in the treatment arm to maintain treatment blinding.

Treatment:

Drug: EBX-102