Vitamin A and D Supplementation in Allogeneic HCT

Phase 2

Recruiting

• Conditions: Acute Lymphoblastic Leukemia; Lymphoblastic Lymphoma; Myelodysplastic Syndromes; Biphenotypic Acute Leukemia; Myeloprolipherative Neoplsm; Non-hodgkin Lymphoma; Acute Myeloid Leukemia; Chronic Myeloid Leukemia
• Interventions: Drug: Vitamin A; Drug: Vitamin D3

• Registration Number: NCT06508099
• Lead Sponsor: St. Petersburg State Pavlov Medical University

Brief Summary

The therapy under investigation is the addition of 300 000 IU of vitamin A and 100 000 IU of vitamin D before conditioning. The study will include patients with malignant diseases in hematologic response with indications for allogeneic transplantation with matched related or matched unrelated donor.

Detailed Description

Currently there is an emerging evidence of gut microbiota role in major complications of HCT, including GVHD, oral mucositis, infectious complications due to multi-drug resistant bacteria in the gut. Early exhaustion of most intestinal bacterial phyla after HSCT is documented in many studies. This effect of intensive anti-infectious therapy is well known. Most authors explain the disruption of intestinal microbiota by massive antibiotic treatment in order to prevent infectious complications due to immune deficiency following HCT. Early decrease in anaerobic bacteria (phylum Firmicutes) is revealed in many studies, with subsequent recovery of these bacterial populations within next 2 months. This time dynamics is in accordance with reported data on depletion of certain anaerobic gut bacteria, e.g., Ruminococcus, Faecalibacterium spp., Roseburia, Blautia post-transplant, being associated with severe complications in HCT patients. These results are in accordance with severe posttransplant dysbiosis at different mucosal sites post-HCT, as shown elsewhere by routine bacteriology techniques. The metabolism of bacteria with positive effect on GVHD includes both vitamin D and vitamin A. It was demonstrated that Ruminococcus abundance is dependent on vitamin A and D intake. Another bacteria genera Faecalibacterium prausnitzii, which is also reported to produce butyrate and reduce GVHD is also dependent on abundance of vitamin A. The big phylum Firmicutes are also dependant on vitamin D and their abundance is reported to be associated with lower incidence of immune complications and suppression of antibiotic-resistant strains. To summarize the idea of the study is based on modulation of gut microbiota, which in term may result in lower incidence of GVHD and toxic complications of HCT.

Study Timeline

• Study Start: 2024-05-15
• Status Verified: 2024-07
• Study First Submitted: 2024-07-12
• Study First Submitted QC: 2024-07-12
• Study First Posted: 2024-07-18
• Last Update Submitted: 2024-07-29
• Last Update Posted: 2024-07-31
• Primary Completion: 2026-05
• Study Completion: 2027-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 220

Inclusion Criteria

• Diagnosis: acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, chronic myeloproliferative disease, chronic myeloid leukemia, lymphoblastic lymphoma, myeloma
• Standard disease risk: less than 5% clonal blasts in the bone marrow and the absence of blast forms in the peripheral blood at the time of inclusion in the study or at least partial response for lymphoproliferative neoplasms.
• Related compatible donor 10/10 HLA-matched or unrelated compatible donor 9-10/10 HLA-matched
• Age ≥18 years
• Absence of severe concomitant somatic diseases

Exclusion Criteria

• • Severe organ failure: creatinine more than 2 norms; ALT, AST more than 5 norms; bilirubin more than 1.5 normal;
• respiratory failure more than 1 degree. or oxygen dependence
• Unstable hemodynamics;
• Uncontrolled bacterial or fungal infection at the time of inclusion, despite adequate antibacterial or antifungal therapy (CRP>70 mg/l at the time of inclusion).
• Karnofsky index less than 70%
• Repeated allogeneic transplantation of hematopoietic cells;
• Creatinine clearance below 60ml/min/1.73m2;
• Severe cardiac pathology, including a decrease in ejection fraction less than <50%, unstable angina, exertional angina of III-IV functional class, heart failure of III-IV functional class, arrhythmia grade V according to Lawn
• Severe decrease in lung function, FEV1 <50% or DLCO<50% predicted
• Pregnancy
• Somatic or mental pathology that does not allow signing informed consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vitamin supplementation	Vitamin A	vitamin A 300 000 IU and vitamin D 100 000 IU on days -14 to -8 before transplantation
Vitamin supplementation	Vitamin D3	vitamin A 300 000 IU and vitamin D 100 000 IU on days -14 to -8 before transplantation

Primary Outcome Measures

Name	Time	Method
Cumulative incidence of gastrointestinal acute GVHD	125 days	Cumulative incidence of patients with acute GVHD II-IV grade, competing risk is death, relapse and primary graft failure

Secondary Outcome Measures

Name	Time	Method
Incidence of HSCT-associated adverse events	125 days	Toxicity assessment is based on presence of NCI CTC AE 5.0 event grades 3-5. Veno-occlusive disease incidence and severity assessment is based on EBMT criteria 2020. Transplant-associated microangiopathy incidence assessment is based on Harmonization criteria. All toxicity measurements will be aggregated as severity scores
Overall survival	2 years	Kaplan-Meier estimate of either relapse, primary or secondary graft failure or death from all causes
Infectious complications	125 days	Incidence of infections, including analysis of severe bacterial, fungal and viral infections incidence
Event-free survival	2 years	Kaplan-Meier estimate of either relapse, primary or secondary graft failure or death from all causes
Incidence of moderate and severe chronic GVHD	2 years	Cumulative incidence of patients with moderate and severe chronic GVHD according to NIH 2015 criteria, competing risk is death, relapse and primary graft failure
Non-relapse mortality analysis	2 years	Cumulative incidence of patients with mortality without hematological relapse of malignancy
GVHD-relapse-free survival analysis	2 years	Kaplan-Meier estimate of death, acute GVHD grade III-IV, severe chronic GVHD or relapse
Cumulative incidence of primary and secondary graft failure	125 days	Cumulative primary and secondary graft failure, competing risk is death and relapse
Overall cumulative incidence of acute GVHD grade II-IV	125 days	Cumulative incidence of patients with acute GVHD II-IV grade, competing risk is death, relapse and primary graft failure

Trial Locations

Locations (1)

RM Gorbacheva Research Institute; 🇷🇺 Saint Petersburg, Russian Federation