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NCT Number: NCT04942730

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

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.

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Key information

Conditions

Leukemia, Acute Lymphoblastic Biphenotypic Acute Leukemia Bone Marrow Diseases Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Leukemia Leukemia, Biphenotypic, Acute Leukemia, Lymphoid Leukemia, Myeloid Leukemia, Myeloid, Acute Lymphatic Diseases Lymphoblastic Lymphoma Lymphoproliferative Disorders Myelodysplastic Syndromes Myeloid Leukemia, Acute Myeloproliferative Disorders Myeloproliferative Neoplasm Neoplasms Neoplasms by Histologic Type Precursor Cell Lymphoblastic Leukemia-Lymphoma

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

RM Gorbacheva Research Institute

Saint Petersburg, 197022, Russia

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Fludarabine

Drug

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

Bendamustine Hydrochloride

Drug

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

busulfan

Drug

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

Cyclophosphamide

Drug

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

Mycophenolate mofetil

Drug

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

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.

Primary outcomes

  1. - Incidence of primary and secondary graft failure

    Time frame: 100 days

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

Secondary outcomes

  1. - Incidence of HSCT-associated adverse events (safety and toxicity)

    Time frame: 125 days

    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.

  2. - Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence

    Time frame: [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]

    Proportion of patients, requiring systemic treatment for bacterial, viral and fungal disease

  3. - Incidence of acute GVHD grade II-IV

    Time frame: 125 days

    Cumulative incidence of patients with acute GVHD II-IV grade

  4. - Incidence of moderate and severe chronic GVHD

    Time frame: 365 days

    Cumulative incidence of patients with moderate and severe chronic GVHD according to NIH 2015 criteria.

  5. - Non-relapse mortality analysis

    Time frame: 2 years

    Cumulative incidence of patients with mortality without hematological relapse of malignancy

  6. - Overall survival analysis

    Time frame: 2 years

    Kaplan-Meier estimate of death from all causes

  7. - Event-free survival analysis

    Time frame: 2 years

    Kaplan-Meier estimate of death or relapse

  8. - Relapse rate analysis

    Time frame: 2 years

    Cumulative incidence of patients with relapse

Sponsors and collaborators

Lead sponsor

St. Petersburg State Pavlov Medical University

Other

Registry information

Acronym: FluBuBe

Important dates

Study start
2021
Primary completion
2024
Study completion
2024
First posted
Jun 28, 2021
Registry last updated
May 7, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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