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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
220
Days -7 through -6: Bendamustine 90 mg/m2 iv x 2 days
Days -7 through -2: ruxolitinib 5 mg tid per os
RM Gorbacheva Research Institute
Saint Petersburg, Russia
RECRUITINGEvent-free survival
Measure: Kaplan-Meier estimate of either relapse, primary or secondary graft failure or death from all causes
Time frame: 2 years
Cumulative incidence of primary and secondary graft failure
Cumulative primary and secondary graft failure, competing risk is death and relapse
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 2 years
Non-relapse mortality analysis
Cumulative incidence of patients with mortality without hematological relapse of malignancy
Time frame: 2 years
Overall survival analysis
Measure: Kaplan-Meier estimate of death from all causes
Time frame: 2 years
GVHD-relapse-free survival analysis
Measure: Kaplan-Meier estimate of death, acute GVHD grade III-IV, severe chronic GVHD or relapse
Time frame: 2 years
Relapse cumulative incidence analysis
Cumulative incidence of patients with relapse, competing risk is non-relapse mortality
Time frame: 2 years
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