BeFluBu vs FluBuRux Conditioning in Haploidentical HCT
NCT Number: NCT06477549
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Acute Lymphoblastic Leukemia|Acute Myeloid Leukemia|Biphenotypic Acute Leukemia|Lymphoblastic Lymphoma|Myeloproliferative Neoplasm|Myelodysplastic Syndromes
Interventions: DRUG: Bendamustine Hydrochloride|DRUG: Ruxolitinib
Sponsor: St. Petersburg State Pavlov Medical University
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 220
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-06-21
Completion Date: 2029-06
Locations: RM Gorbacheva Research Institute, Saint Petersburg, 197022, Russian Federation

Summary:
Haploidentical hematopoietic stem cell transplantation irrespective of the conditioning intensity and graft-versus-host disease prophylaxis is associated with high frequency of primary and secondary graft failure. Different technologies of with replete or depleted graft are associated with 7-20% of graft failures in different diseases. Fludarabine and busulfan conditioning is the most commonly used approach for a variety of diseases. In two previously completed trials of addition of either bendamustine and ruxolitinib to conditioning we observed low rates of primary graft failure with both approaches. The study is the direct randomized comparisons of these two approaches with the primary aim of reducing composite events of primary graft failure, relapse and non-relapse mortality. The stratas for the study are Disease Risk Index (DRI) and the age of the haploidentical donor (\<35 vs ≥35).

Primary Outcome Measures: Event-free survival, Measure: Kaplan-Meier estimate of either relapse, primary or secondary graft failure or death from all causes, 2 years
Secondary Outcome Measures: Cumulative incidence of primary and secondary graft failure, Cumulative primary and secondary graft failure, competing risk is death and relapse, 365 days|Incidence of HSCT-associated adverse events (safety and toxicity), 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 by Schoettler et al. All toxicity measurements will be aggregated as severity scores, 125 days|Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence, proportion of patients, requiring systemic treatment for bacterial, viral and fungal disease, 100 days|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|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|Overall survival analysis, Measure: Kaplan-Meier estimate of death from all causes, 2 years|GVHD-relapse-free survival analysis, Measure: Kaplan-Meier estimate of death, acute GVHD grade III-IV, severe chronic GVHD or relapse, 2 years|Relapse cumulative incidence analysis, Cumulative incidence of patients with relapse, competing risk is non-relapse mortality, 2 years