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

NCT04942730 | Completed Phase 2

• 1 other identifier: 06/21-n
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• - 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 Outcomes (8)

• - 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

Study Arms (1)

FluBuBe

EXPERIMENTAL

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

Drug: Fludarabine; Drug: Bendamustine Hydrochloride; Drug: Busulfan; Drug: Cyclophosphamide; Drug: Mycophenolate Mofetil; Drug: Tacrolimus 5Mg Cap

Interventions

Fludarabine DRUG

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

FluBuBe

Bendamustine Hydrochloride DRUG

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

FluBuBe

Busulfan DRUG

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

FluBuBe

Cyclophosphamide DRUG

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

FluBuBe

Mycophenolate Mofetil DRUG

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

FluBuBe

Tacrolimus 5Mg Cap DRUG

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

FluBuBe

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• St. Petersburg State Pavlov Medical University: lead

Study Sites (1)

RM Gorbacheva Research Institute

Saint Petersburg, 197022, Russia

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Biphenotypic, Acute; Myelodysplastic Syndromes; Myeloproliferative Disorders

Interventions

fludarabine; Bendamustine Hydrochloride; Busulfan; Cyclophosphamide; Mycophenolic Acid; Tacrolimus; Capsules

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Phosphoramides; Organophosphorus Compounds; Caproates; Fatty Acids; Lipids; Macrolides; Lactones; Dosage Forms; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice-pdirector for science RM Gorbacheva Institute

Study Record Dates

• First Submitted: June 21, 2021
• First Posted: June 28, 2021
• Study Start: January 21, 2021
• Primary Completion: April 30, 2024
• Study Completion: April 30, 2024
• Last Updated: May 7, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share

Locations

RU (1)