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

Myelodysplastic Syndromes Clinical Trial

— FluBuBe  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04942730
• Other study ID #: 06/21-n
• Status: Completed
• Phase: Phase 2
• 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
• 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

Related Conditions & MeSH terms

• Acute Disease
• Biphenotypic Acute Leukemia
• Leukemia
• Leukemia, Acute Lymphoblastic
• Leukemia, Biphenotypic, Acute
• Leukemia, Myeloid, Acute
• Lymphoblastic Lymphoma
• Myelodysplastic Syndromes
• Myeloid Leukemia, Acute
• Myeloproliferative Disorders
• Myeloproliferative Neoplasm
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

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