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

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

Sponsors

Lead Sponsor: St. Petersburg State Pavlov Medical University

Source St. Petersburg State Pavlov Medical University
Brief 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.

Overall Status Recruiting
Start Date 2021-01-21
Completion Date 2024-12-31
Primary Completion Date 2023-12-31
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
- Incidence of primary and secondary graft failure 100 days
Secondary Outcome
Measure Time Frame
- Incidence of HSCT-associated adverse events (safety and toxicity) 125 days
- Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
- Incidence of acute GVHD grade II-IV 125 days
- Incidence of moderate and severe chronic GVHD 365 days
- Non-relapse mortality analysis 2 years
- Overall survival analysis 2 years
- Event-free survival analysis 2 years
- Relapse rate analysis 2 years
Enrollment 40
Condition
Intervention

Intervention Type: Drug

Intervention Name: Fludarabine

Description: 30 mg/m2/day iv x 6 days, days -7 through -2 of HSCT

Arm Group Label: FluBuBe

Intervention Type: Drug

Intervention Name: Bendamustine Hydrochloride

Description: 130 mg/m2 iv x 2 days, Days -7 through -6 of HSCT

Arm Group Label: FluBuBe

Intervention Type: Drug

Intervention Name: Busulfan

Description: 1 mg/kg po qid x 3 days, Days -5 through -3

Arm Group Label: FluBuBe

Intervention Type: Drug

Intervention Name: Cyclophosphamide

Description: 50 mg/kg iv x 2 days, Days +3 through +4

Arm Group Label: FluBuBe

Intervention Type: Drug

Intervention Name: Mycophenolate Mofetil

Description: 45 mg/kg/day, maximum 3 g/day, iv or po x 30 days, Days +5 through +35

Arm Group Label: FluBuBe

Intervention Type: Drug

Intervention Name: Tacrolimus 5Mg Cap

Description: 0.03 mg/kg/day iv or po, Days +5 through +100 with with further correction by concentration. Target concentration 5-15 ng/ml.

Arm Group Label: FluBuBe

Eligibility

Criteria:

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

Gender:

All

Minimum Age:

18 Years

Maximum Age:

75 Years

Healthy Volunteers:

No

Overall Contact

Last Name: Ivan S Moiseev, MD, Prof.

Phone: +79217961951

Email: [email protected]

Location
Facility: Status: Contact: Contact Backup: RM Gorbacheva Research Institute Ivan Moiseev +79217961951 [email protected]
Location Countries

Russian Federation

Verification Date

2021-06-01

Responsible Party

Type: Principal Investigator

Investigator Affiliation: St. Petersburg State Pavlov Medical University

Investigator Full Name: Ivan S Moiseev

Investigator Title: Vice-pdirector for science RM Gorbacheva Institute

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: FluBuBe

Type: Experimental

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

Acronym FluBuBe
Patient Data Yes
Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

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