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

Primary Purpose

Leukemia, Acute Lymphoblastic, Myeloid Leukemia, Acute, Biphenotypic Acute Leukemia

Status
Recruiting
Phase
Phase 2
Locations
Russian Federation
Study Type
Interventional
Intervention
Fludarabine
Bendamustine Hydrochloride
Busulfan
Cyclophosphamide
Mycophenolate Mofetil
Tacrolimus 5Mg Cap
Sponsored by
St. Petersburg State Pavlov Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia, Acute Lymphoblastic focused on measuring Fludarabine, Bendamustine, Busulfan, Myeloablative Agonists, Hematopoietic Stem Cell Transplantation, Allogeneic, Antineoplastic Agents, Alkylating

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • RM Gorbacheva Research InstituteRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

FluBuBe

Arm 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

Outcomes

Primary Outcome Measures

- Incidence of primary and secondary graft failure
Proportion of patients with primary and secondary graft failure defined by the absence of donor chimerism

Secondary Outcome Measures

- 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.
- Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence
Proportion of patients, requiring systemic treatment for bacterial, viral and fungal disease
- Incidence of acute GVHD grade II-IV
Cumulative incidence of patients with acute GVHD II-IV grade
- Incidence of moderate and severe chronic GVHD
Cumulative incidence of patients with moderate and severe chronic GVHD according to NIH 2015 criteria.
- Non-relapse mortality analysis
Cumulative incidence of patients with mortality without hematological relapse of malignancy
- Overall survival analysis
Kaplan-Meier estimate of death from all causes
- Event-free survival analysis
Kaplan-Meier estimate of death or relapse
- Relapse rate analysis
Cumulative incidence of patients with relapse

Full Information

First Posted
June 21, 2021
Last Updated
July 19, 2022
Sponsor
St. Petersburg State Pavlov Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT04942730
Brief Title
Benadamustine, Fludarabine and Busulfan Conditioning in Recipients of Haploidentical Stem Cell Transplantation (FluBuBe)
Acronym
FluBuBe
Official Title
Benadamustine, Fludarabine and Busulfan Conditioning in Recipients of Haploidentical Stem Cell Transplantation (FluBuBe)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 21, 2021 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
St. Petersburg State Pavlov Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Acute Lymphoblastic, Myeloid Leukemia, Acute, Biphenotypic Acute Leukemia, Lymphoblastic Lymphoma, Myelodysplastic Syndromes, Myeloproliferative Neoplasm
Keywords
Fludarabine, Bendamustine, Busulfan, Myeloablative Agonists, Hematopoietic Stem Cell Transplantation, Allogeneic, Antineoplastic Agents, Alkylating

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
FluBuBe
Arm Type
Experimental
Arm 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
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
30 mg/m2/day iv x 6 days, days -7 through -2 of HSCT
Intervention Type
Drug
Intervention Name(s)
Bendamustine Hydrochloride
Intervention Description
130 mg/m2 iv x 2 days, Days -7 through -6 of HSCT
Intervention Type
Drug
Intervention Name(s)
Busulfan
Intervention Description
1 mg/kg po qid x 3 days, Days -5 through -3
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
50 mg/kg iv x 2 days, Days +3 through +4
Intervention Type
Drug
Intervention Name(s)
Mycophenolate Mofetil
Intervention Description
45 mg/kg/day, maximum 3 g/day, iv or po x 30 days, Days +5 through +35
Intervention Type
Drug
Intervention Name(s)
Tacrolimus 5Mg Cap
Intervention 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.
Primary Outcome Measure Information:
Title
- Incidence of primary and secondary graft failure
Description
Proportion of patients with primary and secondary graft failure defined by the absence of donor chimerism
Time Frame
100 days
Secondary Outcome Measure Information:
Title
- Incidence of HSCT-associated adverse events (safety and toxicity)
Description
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.
Time Frame
125 days
Title
- Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence
Description
Proportion of patients, requiring systemic treatment for bacterial, viral and fungal disease
Time Frame
[ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
Title
- Incidence of acute GVHD grade II-IV
Description
Cumulative incidence of patients with acute GVHD II-IV grade
Time Frame
125 days
Title
- Incidence of moderate and severe chronic GVHD
Description
Cumulative incidence of patients with moderate and severe chronic GVHD according to NIH 2015 criteria.
Time Frame
365 days
Title
- Non-relapse mortality analysis
Description
Cumulative incidence of patients with mortality without hematological relapse of malignancy
Time Frame
2 years
Title
- Overall survival analysis
Description
Kaplan-Meier estimate of death from all causes
Time Frame
2 years
Title
- Event-free survival analysis
Description
Kaplan-Meier estimate of death or relapse
Time Frame
2 years
Title
- Relapse rate analysis
Description
Cumulative incidence of patients with relapse
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ivan S Moiseev, MD, Prof.
Phone
+79217961951
Email
moisiv@mail.ru
First Name & Middle Initial & Last Name or Official Title & Degree
Alexandr D Kulagin, MD, Prof.
Phone
+78123386265
Email
bmt-director@1spbgmu.ru
Facility Information:
Facility Name
RM Gorbacheva Research Institute
City
Saint Petersburg
ZIP/Postal Code
197022
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ivan Moiseev
Phone
+79217961951
Email
moisiv@mail.ru
First Name & Middle Initial & Last Name & Degree
Alexandr Kulagin
Phone
+78123386265
Email
bmt-director@1spbgmu.ru

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Request for sharing data with the study plan for the data will be evaluated under common conditions by Pavlov University Ethical Committee.

Learn more about this trial

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

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