Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Biphenotypic Acute Leukemia, Chronic Myeloid Leukemia, Lymphoblastic Lymphoma, Myelodysplastic Syndromes, Myeloprolipherative Neoplsm, Non-hodgkin Lymphoma
Conditions
Keywords
allogeneic hematopoietic transplantation, vitamin A, vitamin D
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.
Interventions
DRUGVitamin A
300 000 IU single dose orally
DRUGVitamin D3
100 000 IU single dose orally
Sponsors
St. Petersburg State Pavlov Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Infectious complications | 125 days | Incidence of infections, including analysis of severe bacterial, fungal and viral infections incidence |
| Overall survival | 2 years | Kaplan-Meier estimate of either relapse, primary or secondary graft failure or death from all causes |
| Event-free survival | 2 years | Kaplan-Meier estimate of either relapse, primary or secondary graft failure or death from all causes |
| 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 |
| 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 |
| 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 |
| 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 |
Countries
Russia
Contacts
Primary ContactIVAN SERGEEVICH MOISEEV
Backup ContactIrina Сергеевич Bykova
Outcome results
None listed