Vitamin A and D Supplementation in Allogeneic HCT

Trial Title: Vitamin A and D Supplementation in Allogeneic HCT

NCT ID: NCT06508099

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

Conditions: Official terms:
Lymphoma
Leukemia
Leukemia, Myeloid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Biphenotypic, Acute
Myelodysplastic Syndromes
Vitamin D
Cholecalciferol
Vitamins
Vitamin A

Conditions: Keywords:
allogeneic hematopoietic transplantation
vitamin A
vitamin D

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Vitamin A
Description: 300 000 IU single dose orally
Arm group label: Vitamin supplementation

Intervention type: Drug
Intervention name: Vitamin D3
Description: 100 000 IU single dose orally
Arm group label: Vitamin supplementation

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.

Criteria for eligibility:
Criteria:
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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: RM Gorbacheva Research Institute

Address:
City: Saint Petersburg
Zip: 197022
Country: Russian Federation

Status: Recruiting

Contact:
Last name: Ivan Moiseev

Phone: +79217961951
Email: moisiv@mail.ru

Contact backup:
Last name: Alexandr Kulagin

Phone: +78123386265
Email: bmt-director@1spbgmu.ru

Start date: May 15, 2024

Completion date: May 2027

Lead sponsor:
Agency: St. Petersburg State Pavlov Medical University
Agency class: Other

Source: St. Petersburg State Pavlov Medical University

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06508099