BeFluBu vs FluBuRux Conditioning in Haploidentical HCT
Randomized Trial of Benadamustine Versus Ruxolitinib With Fludarabine and Busulfan Conditioning in Recipients of Haploidentical Stem Cell Transplantation
1 other identifier
interventional
220
1 country
1
Brief 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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jun 2024
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 21, 2024
CompletedStudy Start
First participant enrolled
June 21, 2024
CompletedFirst Posted
Study publicly available on registry
June 27, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 1, 2029
June 27, 2024
June 1, 2024
3.9 years
June 21, 2024
June 21, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
Event-free survival
Measure: Kaplan-Meier estimate of either relapse, primary or secondary graft failure or death from all causes
2 years
Secondary Outcomes (9)
Cumulative incidence of primary and secondary graft failure
365 days
Incidence of HSCT-associated adverse events (safety and toxicity)
125 days
Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence
100 days
Cumulative incidence of acute GVHD grade II-IV
125 days
Incidence of moderate and severe chronic GVHD
2 years
- +4 more secondary outcomes
Study Arms (2)
FluBeBu conditioning
EXPERIMENTALDays -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days; Days -7 through -6: Bendamustine 90 mg/m2 iv x 2 days; Days -5 through -3: Busulfan 1 mg/kg po qid x 3 days;Days +3 through +4: Cyclophosphamide 50 mg/kg iv x 2 days; Days +5 through +20: ruxolitinib 5 mg tid per os; Days +21 through 150: ruxolitinib 5 mg bid per os.
FluBeRux conditioning
ACTIVE COMPARATORDays -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days; Days -7 through -2: ruxolitinib 5 mg tid per os; Days -5 through -3: Busulfan 1 mg/kg po qid x 3 days; Days +3 through +4: Cyclophosphamide 50 mg/kg iv x 2 days; Days +5 through +20: ruxolitinib 5 mg tid per os; Days +21 through 150: ruxolitinib 5 mg bid per os.
Interventions
Days -7 through -6: Bendamustine 90 mg/m2 iv x 2 days
Eligibility Criteria
You may qualify if:
- Patients must have an indication for allogeneic hematopoietic stem cell transplantation with myeloablative conditioning for malignant disease
- Diagnosis: acute myeloid leukemia, acute lymphoblastic leukemia, mixed lineage acute leukemia, lymphoblastic lymphoma, chronic myeloid leukemia, myelodysplastic syndromes, myeloprolipherative neoplasm
- Age ≥18
- Malignant disease in hematologic response: \<5% of clonal blasts in the bone marrow and no clonal blasts in peripheral blood.
- Patients with 5-9/10 HLA-matched related donor available. The donor and recipient must be identical by the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1.
- Peripheral blood stem cells or bone marrow as a graft source
You may not qualify if:
- Severe decrease in pulmonary function: FEV1 \<50% or DLCO\<50% of predicted or respiratory distress or need for oxygen support;
- Severe organ dysfunction: AST or ALT \>5 upper normal limits, bilirubin \>1.5 upper normal limits, creatinine \>2 upper normal limits
- Creatinine clearance \< 40 mL/min
- Uncontrolled bacterial or fungal infection at the time of enrollment defined by CRP\> 70 mg/L
- Requirement for vasopressor support at the time of enrollment
- Karnofsky index \<70%
- Pregnancy
- Somatic or psychiatric disorder making the patient unable to sign informed consent
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
RM Gorbacheva Research Institute
Saint Petersburg, 197022, Russia
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Vice-director of RM Gorbacheva Research Institute
Study Record Dates
First Submitted
June 21, 2024
First Posted
June 27, 2024
Study Start
June 21, 2024
Primary Completion (Estimated)
June 1, 2028
Study Completion (Estimated)
June 1, 2029
Last Updated
June 27, 2024
Record last verified: 2024-06
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL
- Time Frame
- After final study analysis availability for 15 years
- Access Criteria
- Written proposal to the department of scientific affairs of Pavlov University with a subsequent signed contract for research
Written proposal to the department of scientific affairs of Pavlov University with a subsequent signed contract for research