BeFluBu vs FluBuRux Conditioning in Haploidentical HCT

Phase 2

Recruiting

• Conditions: Acute Lymphoblastic Leukemia; Biphenotypic Acute Leukemia; Myelodysplastic Syndromes; Lymphoblastic Lymphoma; Acute Myeloid Leukemia; Myeloproliferative Neoplasm
• Interventions: Drug: Bendamustine Hydrochloride; Drug: Ruxolitinib

• Registration Number: NCT06477549
• Lead Sponsor: St. Petersburg State Pavlov Medical University

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 busulf...

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Status Verified: 2024-06
• Study Start: 2024-06-21
• Study First Submitted: 2024-06-21
• Study First Submitted QC: 2024-06-21
• Last Update Submitted: 2024-06-21
• Study First Posted: 2024-06-27
• Last Update Posted: 2024-06-27
• Primary Completion: 2028-06
• Study Completion: 2029-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 220

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FluBeBu conditioning	Bendamustine Hydrochloride	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.
FluBeRux conditioning	Ruxolitinib	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.

Primary Outcome Measures

Name	Time	Method
Event-free survival	2 years	Measure: Kaplan-Meier estimate of either relapse, primary or secondary graft failure or death from all causes

Secondary Outcome Measures

Name	Time	Method
Incidence of moderate and severe chronic GVHD	2 years	Cumulative incidence of patients with moderate and severe chronic GVHD according to NIH 2015 criteria, competing risk is death, relapse and primary graft failure
Overall survival analysis	2 years	Measure: Kaplan-Meier estimate of death from all causes
Cumulative incidence of primary and secondary graft failure	365 days	Cumulative primary and secondary graft failure, competing risk is death and relapse
Incidence of HSCT-associated adverse events (safety and toxicity)	125 days	Toxicity assessment is based on presence of NCI CTC AE 5.0 event grades 3-5. Veno-occlusive disease incidence and severity assessment is based on EBMT criteria 2020. Transplant-associated microangiopathy incidence assessment is based on Harmonization criteria by Schoettler et al. All toxicity measurements will be aggregated as severity scores
Non-relapse mortality analysis	2 years	Cumulative incidence of patients with mortality without hematological relapse of malignancy
Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence	100 days	proportion of patients, requiring systemic treatment for bacterial, viral and fungal disease
Relapse cumulative incidence analysis	2 years	Cumulative incidence of patients with relapse, competing risk is non-relapse mortality
Cumulative incidence of acute GVHD grade II-IV	125 days	Cumulative incidence of patients with acute GVHD II-IV grade, competing risk is death, relapse and primary graft failure
GVHD-relapse-free survival analysis	2 years	Measure: Kaplan-Meier estimate of death, acute GVHD grade III-IV, severe chronic GVHD or relapse

Trial Locations

Locations (1)

RM Gorbacheva Research Institute; 🇷🇺 Saint Petersburg, Russian Federation