Clinical trial NCT06355583: Intestinal Microbiota Transplant Prior to Allogeneic Stem Cell Transplant (MAST) Trial
Official title: Intestinal Microbiota Transplant Prior to Allogeneic Stem Cell Transplant (MAST) Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Lymphoblastic Leukaemia
Acute Leukemia of Ambiguous Lineage
Chronic Myeloid Leukemia
Chronic Myelomonocytic Leukemia
Myelodysplastic Syndrome
Acute Myeloid Leukemia
Keywords: MAST
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2024-04-09
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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.

Primary outcomes:
measure: Change in gut microbiota diversity using Inverse Simpsons Index
timeFrame: Screening - up to 42 before stem cell transplantation (HCT) and Assessment 5 - Day 28(+/-3) post stem cell transplantation (HCT)
Secondary outcomes:
measure: Gut Microbiome Diversity - Alpha diversity
timeFrame: 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)
measure: Alpha Diversity - Chao1 Index
timeFrame: 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)
measure: Alpha Diversity - Shannon Index
timeFrame: 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)
measure: Alpha Diversity - Faiths Phylogenetic Diversity (Faiths PD)
timeFrame: 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)
measure: Beta Diversity - Aitchison Distance
timeFrame: 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)
measure: Gut Microbiome Taxonomic Composition
timeFrame: 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)
measure: Markers of general health - ITU Admission
timeFrame: Days Post HCT: Day 28(+/-3), Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14)
measure: Quality of life EQ-5D-5L
timeFrame: Screening up to Day-42, Days Post HCT: Day 28(+/-3), Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14)
measure: Quality of Life EORTC-QLQ-C30
timeFrame: Screening up to Day-42, Days Post HCT: Day 28(+/-3), Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14)
measure: Infective Haematological Outcomes - Fever Occurrence
timeFrame: 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)
measure: Infective Haematological Outcomes - Fever CTCAE Grade
timeFrame: 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)
measure: Infective Haematological Outcomes - Infection
timeFrame: 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)
measure: Infective Haematological Outcomes - Multi drug Resistant Bacterial Colonisation (MDROs)
timeFrame: 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)
measure: Infective Haematological Outcomes - Antibiotic Use
timeFrame: 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)
measure: Markers of General Health - Severity of Mucositis
timeFrame: 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)
measure: Markers of General Health -Occurrence of Severe Acute Kidney Injury (AKI)
timeFrame: 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)
measure: Markers of General Health - Occurrence of Severe liver dysfunction
timeFrame: 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)
measure: Markers of general health - Use of Parenteral Nutrition
timeFrame: 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)
measure: Neutrophil and platelet engraftment data
timeFrame: Days Post HCT: Day 28(+/-3), Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14)
measure: Recovery of T-cell Chimaerisms,
timeFrame: Follow up Assessments: Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14)
measure: Haematological Outcomes - Non-relapsed mortality
timeFrame: Days Post HCT: Day 28(+/-3), Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14)
measure: Haematological Outcomes - Occurrence Graft vs Host Disease
timeFrame: Follow up Assessments: Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14)
measure: Haematological Outcomes - Severity of graft vs Host Disease
timeFrame: Follow up Assessments: Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14)
measure: Overall Survival
timeFrame: Days Post HCT: Day 28(+/-3), Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14)
measure: Graft-versus disease-free relapse-free survival
timeFrame: Days Post HCT: Day 28(+/-3), Day 100(+/-7), Day 200(+/-7) & Day 365(+/-14)
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
state: England
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospital NHS Trust
state: England
city: London
country: United Kingdom
facility: University College London Hospitals NHS Trust
state: England
city: London
country: United Kingdom
facility: Kings College NHS Foundation Trust
state: England
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
state: England
city: London
country: United Kingdom
facility: Royal Mardsen Hostpital
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: Manchester University NHS Trust
Study officials:
affiliation: Imperial College London
name: Jiri Pavlu
role: PRINCIPAL_INVESTIGATOR
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