Vitamin A and D Supplementation in Allogeneic HCT (VitaStem)

Randomized Study of Vitamin A and D Prophylaxis Before Allogeneic Related and Unrelated Hematopoietic Stem Cell Transplantation

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes; Acute Lymphoblastic Leukemia; Lymphoblastic Lymphoma; Chronic Myeloid Leukemia; Non-hodgkin Lymphoma; Biphenotypic Acute Leukemia; Myeloprolipherative Neoplsm
• Intervention / Treatment: Drug: Vitamin A; Drug: Vitamin D3

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 Type: Interventional
• Enrollment (Estimated): 220
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: IVAN SERGEEVICH MOISEEV; Phone Number: +78123386265; Email: moisiv@mail.ru
• Study Contact Backup: Name: Irina Сергеевич Bykova; Phone Number: +78123386617; Email: bmt-director@1spbgmu.ru

Study Locations

• Russian Federation
  • Saint Petersburg, Russian Federation, 197022
    • Recruiting
    • RM Gorbacheva Research Institute
    • Contact: Alexandr Kulagin; Phone Number: +78123386265; Email: bmt-director@1spbgmu.ru
    • Contact: Ivan Moiseev; Phone Number: +79217961951; Email: moisiv@mail.ru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Routine care
Experimental: Vitamin supplementation; vitamin A 300 000 IU and vitamin D 100 000 IU on days -14 to -8 before transplantation	Drug: Vitamin A; 300 000 IU single dose orally; Drug: Vitamin D3; 100 000 IU single dose orally

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of moderate and severe chronic GVHD	Cumulative incidence of patients with moderate and severe chronic GVHD according to NIH 2015 criteria, competing risk is death, relapse and primary graft failure	2 years
Non-relapse mortality analysis	Cumulative incidence of patients with mortality without hematological relapse of malignancy	2 years
Infectious complications	Incidence of infections, including analysis of severe bacterial, fungal and viral infections incidence	125 days
Overall survival	Kaplan-Meier estimate of either relapse, primary or secondary graft failure or death from all causes	2 years
Event-free survival	Kaplan-Meier estimate of either relapse, primary or secondary graft failure or death from all causes	2 years
Overall cumulative incidence of acute GVHD grade II-IV	Cumulative incidence of patients with acute GVHD II-IV grade, competing risk is death, relapse and primary graft failure	125 days
GVHD-relapse-free survival analysis	Kaplan-Meier estimate of death, acute GVHD grade III-IV, severe chronic GVHD or relapse	2 years
Cumulative incidence of primary and secondary graft failure	Cumulative primary and secondary graft failure, competing risk is death and relapse	125 days
Incidence of HSCT-associated adverse events	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	125 days

Collaborators and Investigators

• Sponsor: St. Petersburg State Pavlov Medical University

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2024
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: July 12, 2024
• First Submitted That Met QC Criteria: July 12, 2024
• First Posted (Actual): July 18, 2024

Study Record Updates

• Last Update Posted (Actual): July 31, 2024
• Last Update Submitted That Met QC Criteria: July 29, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: vitamin D; vitamin A; allogeneic hematopoietic transplantation
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia, Lymphoid; Chronic Disease; Lymphoma; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Biphenotypic, Acute; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Vitamin A
• Other Study ID Numbers: 18/24-n

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Written study proposal to Pavlov University Ethical Committee.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No