Biphenotypic Acute Leukemia, Leukemia, Acute Lymphoblastic, Lymphoblastic Lymphoma, Myelodysplastic Syndromes, Myeloid Leukemia, Acute, Myeloproliferative Neoplasm
Conditions
Keywords
Fludarabine, Bendamustine, Busulfan, Myeloablative Agonists, Hematopoietic Stem Cell Transplantation, Allogeneic, Antineoplastic Agents, Alkylating
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.
Interventions
DRUGFludarabine
30 mg/m2/day iv x 6 days, days -7 through -2 of HSCT
DRUGBendamustine Hydrochloride
130 mg/m2 iv x 2 days, Days -7 through -6 of HSCT
DRUGBusulfan
1 mg/kg po qid x 3 days, Days -5 through -3
DRUGCyclophosphamide
50 mg/kg iv x 2 days, Days +3 through +4
DRUGMycophenolate Mofetil
45 mg/kg/day, maximum 3 g/day, iv or po x 30 days, Days +5 through +35
DRUGTacrolimus 5Mg Cap
0.03 mg/kg/day iv or po, Days +5 through +100 with with further correction by concentration. Target concentration 5-15 ng/ml.
Sponsors
St. Petersburg State Pavlov Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| - Incidence of primary and secondary graft failure | 100 days | Proportion of patients with primary and secondary graft failure defined by the absence of donor chimerism |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| - Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence | [ Time Frame: 100 days ] [ Designated as safety issue: Yes ] | Proportion of patients, requiring systemic treatment for bacterial, viral and fungal disease |
| - Incidence of acute GVHD grade II-IV | 125 days | Cumulative incidence of patients with acute GVHD II-IV grade |
| - Incidence of moderate and severe chronic GVHD | 365 days | Cumulative incidence of patients with moderate and severe chronic GVHD according to NIH 2015 criteria. |
| - Incidence of HSCT-associated adverse events (safety and toxicity) | 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. |
| - Overall survival analysis | 2 years | Kaplan-Meier estimate of death from all causes |
| - Event-free survival analysis | 2 years | Kaplan-Meier estimate of death or relapse |
| - Relapse rate analysis | 2 years | Cumulative incidence of patients with relapse |
| - Non-relapse mortality analysis | 2 years | Cumulative incidence of patients with mortality without hematological relapse of malignancy |
Countries
Russia
Outcome results
None listed