Vitamin A and D Supplementation in Allogeneic HCT (VitaStem)

St. Petersburg State Pavlov Medical University

Status and phase: Enrolling; Phase 2

Conditions: Myeloprolipherative Neoplsm; Non-hodgkin Lymphoma; Lymphoblastic Lymphoma; Chronic Myeloid Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndromes; Biphenotypic Acute Leukemia; Acute Myeloid Leukemia

Treatments: Drug: Vitamin D3; Drug: Vitamin A

Study type: Interventional

Funder types: Other

Identifiers

NCT06508099

18/24-n

Details and patient eligibility

About

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.

Full 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.

Enrollment: 220 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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220 participants in 2 patient groups

Vitamin supplementation

Experimental group

Description:

vitamin A 300 000 IU and vitamin D 100 000 IU on days -14 to -8 before transplantation

Treatment:

Drug: Vitamin A

Drug: Vitamin D3

Routine care

No Intervention group

Description:

Routine care