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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04942730
Other study ID # 06/21-n
Secondary ID
Status Completed
Phase Phase 2
First received
Last updated
Start date January 21, 2021
Est. completion date April 30, 2024

Study information

Verified date May 2024
Source St. Petersburg State Pavlov Medical University
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Recruitment information / eligibility

Status Completed
Enrollment 50
Est. completion date April 30, 2024
Est. primary completion date April 30, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years to 75 Years
Eligibility 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

Study Design


Intervention

Drug:
Fludarabine
30 mg/m2/day iv x 6 days, days -7 through -2 of HSCT
Bendamustine Hydrochloride
130 mg/m2 iv x 2 days, Days -7 through -6 of HSCT
Busulfan
1 mg/kg po qid x 3 days, Days -5 through -3
Cyclophosphamide
50 mg/kg iv x 2 days, Days +3 through +4
Mycophenolate Mofetil
45 mg/kg/day, maximum 3 g/day, iv or po x 30 days, Days +5 through +35
Tacrolimus 5Mg Cap
0.03 mg/kg/day iv or po, Days +5 through +100 with with further correction by concentration. Target concentration 5-15 ng/ml.

Locations

Country Name City State
Russian Federation RM Gorbacheva Research Institute Saint Petersburg

Sponsors (1)

Lead Sponsor Collaborator
St. Petersburg State Pavlov Medical University

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type Measure Description Time frame Safety issue
Primary - Incidence of primary and secondary graft failure Proportion of patients with primary and secondary graft failure defined by the absence of donor chimerism 100 days
Secondary - Incidence of HSCT-associated adverse events (safety and toxicity) Toxicity assessment is based on NCI CTC AE 5.0 grades. Veno-occlusive disease incidence and severity assessment is based on EBMT criteria 2016. Transplant-associated microangiopathy incidence assessment is based on Cho et al. criteria. All toxicity measurements will be aggregated as severity scores. 125 days
Secondary - Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence Proportion of patients, requiring systemic treatment for bacterial, viral and fungal disease [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
Secondary - Incidence of acute GVHD grade II-IV Cumulative incidence of patients with acute GVHD II-IV grade 125 days
Secondary - Incidence of moderate and severe chronic GVHD Cumulative incidence of patients with moderate and severe chronic GVHD according to NIH 2015 criteria. 365 days
Secondary - Non-relapse mortality analysis Cumulative incidence of patients with mortality without hematological relapse of malignancy 2 years
Secondary - Overall survival analysis Kaplan-Meier estimate of death from all causes 2 years
Secondary - Event-free survival analysis Kaplan-Meier estimate of death or relapse 2 years
Secondary - Relapse rate analysis Cumulative incidence of patients with relapse 2 years
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