Benadamustine, Fludarabine and Busulfan Conditioning in Recipients of Haploidentical Stem Cell Transplantation (FluBuBe)

St. Petersburg State Pavlov Medical University

Status and phase: Completed; Phase 2

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

Treatments: Drug: Busulfan; Drug: Bendamustine Hydrochloride; Drug: Fludarabine; Drug: Tacrolimus 5Mg Cap; Drug: Cyclophosphamide; Drug: Mycophenolate Mofetil

Study type: Interventional

Funder types: Other

Identifiers

NCT04942730

06/21-n

Details and patient eligibility

About

Haploidentical hematopoietic stem cell transplantation irrespective of the conditioning 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 10-20% of graft failures. Fludarabine and busulfan conditioning is the most commonly used approach for a variety of disease. Furthermore combination of fludarabine and bendamustine was sufficient to facilitate engraftment in patients with chronic lymphocytic leukemia and lymphomas. The aim of the study is to evaluate whether addition of bendamustine to fladarabine and busulfan conditioning reduces the risk of primary graft failure after haploidentical allograft.

Enrollment: 50 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
• 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
• No second malignancies requiring treatment
• No severe concurrent illness

Exclusion criteria

• Titer of anti-HLA antibodies ≥ 5000 at the time of inclusion
• Moderate or severe cardiac dysfunction, left ventricular ejection fraction <50%
• Moderate or severe decrease in pulmonary function, FEV1 <70% or DLCO<70% of predicted
• Respiratory distress >grade I
• Severe organ dysfunction: AST or ALT >5 upper normal limits, bilirubin >1.5 upper normal limits, creatinine >2 upper normal limits
• Creatinine clearance < 60 mL/min
• Uncontrolled bacterial or fungal infection at the time of enrollment
• Requirement for vasopressor support at the time of enrollment
• Karnofsky index <30%
• Pregnancy
• Somatic or psychiatric disorder making the patient unable to sign informed consent

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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50 participants in 1 patient group

FluBuBe

Experimental group

Description:

Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days; Days -7 through -6: Bendamustine 130 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 +35: Mycophenolate mofetil 45 mg/kg/day, maximum 3 g/day, iv or po x 30 days; Days +5 through +150: Tacrolimus 0.03 mg/kg/day with further correction by concentration

Treatment:

Drug: Busulfan

Drug: Bendamustine Hydrochloride

Drug: Fludarabine

Drug: Cyclophosphamide

Drug: Tacrolimus 5Mg Cap

Drug: Mycophenolate Mofetil