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

Imperial College London8 sites in 1 country50 target enrollmentMay 1, 2024

ConditionsAcute Lymphoblastic Leukaemia Acute Leukemia of Ambiguous Lineage Chronic Myeloid Leukemia Chronic Myelomonocytic Leukemia Myelodysplastic Syndrome Acute Myeloid Leukemia

InterventionsPlacebo EBX-102

DrugsEBX-102 Placebo

Overview

Phase: Phase 2
Intervention: Placebo
Conditions: Acute Lymphoblastic Leukaemia
Sponsor: Imperial College London
Enrollment: 50
Locations: 8
Primary Endpoint: Change in gut microbiota diversity using Inverse Simpsons Index
Status: Recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

May 1, 2024

End Date

May 1, 2027

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Imperial College London

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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).
•Patients must have completed minimum of two cycles of intensive chemotherapy prior to trial enrolment (Appendix 1)
•Patients must have received broad-spectrum antibiotics within 3 months prior to trial enrolment
•Patients must be considered suitable/fit to undergo allogeneic hematopoietic cell transplantation (HCT) as clinically judged by the Local investigator
•Patients with an Karnofsky performance status score 60 or above (Appendix 3)
•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

Exclusion Criteria

•Patients with contraindications to receiving allogeneic HCT.
•Female patients who are pregnant or breastfeeding. All women of childbearing potential must have a negative pregnancy test before commencing treatment.
•Adults of reproductive potential not willing to use appropriate, highly effective, contraception during the specified period.
•Patients with renal or hepatic impairment as clinically judged by the Local Investigator.
•Patients with active infection, HIV-positive or chronic active hepatitis B virus (HBV) or hepatitis C virus (HCV).
•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.
•Swallowing difficulties that may preclude safe use of IMT capsules.
•Administration of IMT within 3 months prior to enrolment (probiotic administration prior to enrolment is allowed but should be recorded at screening).
•Patients taking probiotics after enrolment to the trial.
•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.

Arms & Interventions

Placebo

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.

Intervention: Placebo

EBX-102-02

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.

Intervention: EBX-102

Outcomes

Primary Outcomes

Change in gut microbiota diversity using Inverse Simpsons Index

Time Frame: Screening - up to 42 before stem cell transplantation (HCT) and Assessment 5 - Day 28(+/-3) post stem cell transplantation (HCT)

Ecological metric to measure diversity in the gut microbiome in samples collected at two time points. It considers both the number of species present (richness) and their relative abundance (evenness). The Inverse index scale ranges from 0-1 with higher ranges indicating higher diversity.

Secondary Outcomes

Gut Microbiome Diversity - Alpha diversity(All timepoints, Screening up to Day-42, Day -7(+/-2), Day 0(+/-1), Day 7(+/-3), Day 14(+/-3), Day 28(+/-3), Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14))
Alpha Diversity - Chao1 Index(All timepoints, Screening up to Day-42, Day -7(+/-2), Day 0(+/-1), Day 7(+/-3), Day 14(+/-3), Day 28(+/-3), Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14))
Alpha Diversity - Shannon Index(All timepoints, Screening up to Day-42, Day -7(+/-2), Day 0(+/-1), Day 7(+/-3), Day 14(+/-3), Day 28(+/-3), Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14))
Alpha Diversity - Faiths Phylogenetic Diversity (Faiths PD)(All timepoints, Screening up to Day-42, Day -7(+/-2), Day 0(+/-1), Day 7(+/-3), Day 14(+/-3), Day 28(+/-3), Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14))
Markers of general health - Use of Parenteral Nutrition(The outcome will be assessed at Day -7(+/-2), Day 0(+/-1), Day 7(+/-3), Day 14(+/-3), Day 28(+/-3), Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14))
Beta Diversity - Aitchison Distance(All timepoints, Screening up to Day-42, Day -7(+/-2), Day 0(+/-1), Day 7(+/-3), Day 14(+/-3), Day 28(+/-3), Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14))
Gut Microbiome Taxonomic Composition(All timepoints, Screening up to Day-42, Day -7(+/-2), Day 0(+/-1), Day 7(+/-3), Day 14(+/-3), Day 28(+/-3), Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14))
Markers of general health - ITU Admission(Days Post HCT: Day 28(+/-3), Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14))
Quality of life EQ-5D-5L(Screening up to Day-42, Days Post HCT: Day 28(+/-3), Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14))
Quality of Life EORTC-QLQ-C30(Screening up to Day-42, Days Post HCT: Day 28(+/-3), Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14))
Infective Haematological Outcomes - Fever Occurrence(All timepoints, Screening up to Day-42, Day -7(+/-2), Day 0(+/-1), Day 7(+/-3), Day 14(+/-3), Day 28(+/-3), Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14))
Infective Haematological Outcomes - Fever CTCAE Grade(All timepoints, Screening up to Day-42, Day -7(+/-2), Day 0(+/-1), Day 7(+/-3), Day 14(+/-3), Day 28(+/-3), Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14))
Infective Haematological Outcomes - Infection(All timepoints, Screening up to Day-42, Day -7(+/-2), Day 0(+/-1), Day 7(+/-3), Day 14(+/-3), Day 28(+/-3), Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14))
Infective Haematological Outcomes - Multi drug Resistant Bacterial Colonisation (MDROs)(All timepoints, Screening up to Day-42, Day -7(+/-2), Day 0(+/-1), Day 7(+/-3), Day 14(+/-3), Day 28(+/-3), Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14))
Infective Haematological Outcomes - Antibiotic Use(All timepoints, Screening up to Day-42, Day -7(+/-2), Day 0(+/-1), Day 7(+/-3), Day 14(+/-3), Day 28(+/-3), Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14))
Markers of General Health - Severity of Mucositis(The outcome will be assessed at Day -7(+/-2), Day 0(+/-1), Day 7(+/-3), Day 14(+/-3), Day 28(+/-3), Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14))
Markers of General Health -Occurrence of Severe Acute Kidney Injury (AKI)(The outcome will be assessed at Day -7(+/-2), Day 0(+/-1), Day 7(+/-3), Day 14(+/-3), Day 28(+/-3), Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14))
Markers of General Health - Occurrence of Severe liver dysfunction(The outcome will be assessed at Day -7(+/-2), Day 0(+/-1), Day 7(+/-3), Day 14(+/-3), Day 28(+/-3), Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14))
Neutrophil and platelet engraftment data(Days Post HCT: Day 28(+/-3), Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14))
Recovery of T-cell Chimaerisms,(Follow up Assessments: Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14))
Haematological Outcomes - Non-relapsed mortality(Days Post HCT: Day 28(+/-3), Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14))
Haematological Outcomes - Occurrence Graft vs Host Disease(Follow up Assessments: Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14))
Haematological Outcomes - Severity of graft vs Host Disease(Follow up Assessments: Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14))
Overall Survival(Days Post HCT: Day 28(+/-3), Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14))
Graft-versus disease-free relapse-free survival(Days Post HCT: Day 28(+/-3), Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14))