Clinical trial NCT06477549: BeFluBu vs FluBuRux Conditioning in Haploidentical HCT
Official title: Randomized Trial of Benadamustine Versus Ruxolitinib With Fludarabine and Busulfan Conditioning in Recipients of Haploidentical Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Lymphoblastic Leukemia
Acute Myeloid Leukemia
Biphenotypic Acute Leukemia
Lymphoblastic Lymphoma
Myeloproliferative Neoplasm
Myelodysplastic Syndromes
Lead sponsor: St. Petersburg State Pavlov Medical University
Sponsor class: OTHER
First posted: 2024-06-27
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* Titer of anti-donor anti-HLA antibodies ≥ 5000 at the time of inclusion
* Moderate or severe cardiac disease: ejection fraction \<50%, unstable angina, stable angina NYHA class III or IV, chronic heart failure NYHA class III or IV, Lawn grade V arrhythmia, myocardial infarction within 3 months before inclusion
* Stroke within 3 months of inclusion, unless related to the underlying malignancy
* 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

Primary outcomes:
measure: Event-free survival
timeFrame: 2 years
Secondary outcomes:
measure: Cumulative incidence of primary and secondary graft failure
timeFrame: 365 days
measure: Incidence of HSCT-associated adverse events (safety and toxicity)
timeFrame: 125 days
measure: Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence
timeFrame: 100 days
measure: Cumulative incidence of acute GVHD grade II-IV
timeFrame: 125 days
measure: Incidence of moderate and severe chronic GVHD
timeFrame: 2 years
measure: Non-relapse mortality analysis
timeFrame: 2 years
measure: Overall survival analysis
timeFrame: 2 years
measure: GVHD-relapse-free survival analysis
timeFrame: 2 years
measure: Relapse cumulative incidence analysis
timeFrame: 2 years
Other outcomes:
Locations:
city: Saint Petersburg
country: Russian Federation
facility: RM Gorbacheva Research Institute
Study officials:
References: