BeFluBu vs FluBuRux Conditioning in Haploidentical HCT

Trial Title: BeFluBu vs FluBuRux Conditioning in Haploidentical HCT

NCT ID: NCT06477549

Condition: Acute Lymphoblastic Leukemia
Acute Myeloid Leukemia
Biphenotypic Acute Leukemia
Lymphoblastic Lymphoma
Myeloproliferative Neoplasm
Myelodysplastic Syndromes

Conditions: Official terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Biphenotypic, Acute
Myelodysplastic Syndromes
Myeloproliferative Disorders
Bendamustine Hydrochloride

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Bendamustine Hydrochloride
Description: Days -7 through -6: Bendamustine 90 mg/m2 iv x 2 days
Arm group label: FluBeBu conditioning

Intervention type: Drug
Intervention name: Ruxolitinib
Description: Days -7 through -2: ruxolitinib 5 mg tid per os
Arm group label: FluBeRux conditioning

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).

Criteria for 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

Gender: All

Minimum age: 18 Years

Maximum age: 75 Years

Healthy volunteers: No

Locations:

Facility:
Name: RM Gorbacheva Research Institute

Address:
City: Saint Petersburg
Zip: 197022
Country: Russian Federation

Status: Recruiting

Contact:
Last name: Ivan Moiseev

Phone: +79217961951
Email: moisiv@mail.ru

Contact backup:
Last name: Alexandr Kulagin

Phone: +78123386265
Email: bmt-director@1spbgmu.ru

Start date: June 21, 2024

Completion date: June 2029

Lead sponsor:
Agency: St. Petersburg State Pavlov Medical University
Agency class: Other

Source: St. Petersburg State Pavlov Medical University

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06477549