Clinical trial NCT04942730: Benadamustine, Fludarabine and Busulfan Conditioning in Recipients of Haploidentical Stem Cell Transplantation (FluBuBe)
Official title: Benadamustine, Fludarabine and Busulfan Conditioning in Recipients of Haploidentical Stem Cell Transplantation (FluBuBe)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: St. Petersburg State Pavlov Medical University
Sponsor class: OTHER
First posted: 2021-06-28
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: - Incidence of primary and secondary graft failure
timeFrame: 100 days
Secondary outcomes:
measure: - Incidence of HSCT-associated adverse events (safety and toxicity)
timeFrame: 125 days
measure: - Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence
timeFrame: [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
measure: - Incidence of acute GVHD grade II-IV
timeFrame: 125 days
measure: - Incidence of moderate and severe chronic GVHD
timeFrame: 365 days
measure: - Non-relapse mortality analysis
timeFrame: 2 years
measure: - Overall survival analysis
timeFrame: 2 years
measure: - Event-free survival analysis
timeFrame: 2 years
measure: - Relapse rate analysis
timeFrame: 2 years
Other outcomes:
Locations:
city: Saint Petersburg
country: Russian Federation
facility: RM Gorbacheva Research Institute
Study officials:
References: