BeFluBu vs FluBuRux Conditioning in Haploidentical HCT

St. Petersburg State Pavlov Medical University

Status and phase: Enrolling; Phase 2

Conditions: Myeloproliferative Neoplasm; Lymphoblastic Lymphoma; Acute Lymphoblastic Leukemia; Myelodysplastic Syndromes; Biphenotypic Acute Leukemia; Acute Myeloid Leukemia

Treatments: Drug: Ruxolitinib; Drug: Bendamustine Hydrochloride

Study type: Interventional

Funder types: Other

Identifiers

NCT06477549

14/24-n

Details and patient eligibility

About

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).

Enrollment: 220 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

220 participants in 2 patient groups

FluBeBu conditioning

Experimental group

Description:

Days -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.

Treatment:

Drug: Bendamustine Hydrochloride

FluBeRux conditioning

Active Comparator group

Description:

Days -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.

Treatment:

Drug: Ruxolitinib