Optimization of bendamustine-containg graft-versus-host disease (GVHD) prophylaxis to reduce the incidence of secondary haemophagocytic lymphohistiocytosis and GVHD
Prognosis of patients undergoing allogeneic stem cell transplantation (HCT) for high-risk myeloid malignancies, including refractory acute myeloid leukemia, with standard HCT technologies have relatively poor prognosis with 10-30% long-term disease-free survival. One of the approaches to augment graft-versus-leukemia effect the use of post-transplantation bendamustine in graft-versus-host disease prophylaxis. Despite high frequency of responses and durable remissions after this approach majority of patients develop a serious complication - cytokine release syndrome, which can be life-threatening in some patients. The combination bendamustine (PTB) and post-transplantation cyclophosphamide (PTCY) facilitates comparable graft-versus leukemia effect to PTB, but with better safety profile and reduced incidence of severe cytokine release syndrome.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
; Days -1 through +21: ruxolitinib 10 mg/kg/day p.o.
Days -1,+5, +14, +21 abatacept 10 mg/kg/day i.v.
Pavlov University
Saint Petersburg, Russia
RECRUITINGOverall survival analysis
Measure: Kaplan-Meier estimate of death from all causes
Time frame: 2 years
Incidence of secondary hemophagocytic lymphohistiocytosis
Based on H-score diagnostic criteria.
Time frame: 100 days
Incidence of HSCT-associated adverse events (safety and toxicity)
Toxicity assessment is based on NCI CTC AE 6.0 grades. Veno-occlusive disease incidence and severity assessment is based on EBMT criteria 2016. Transplant-associated microangiopathy incidence assessment is based on Schoettler et al. criteria. All toxicity measurements will be aggregated as severity scores.
Time frame: 100 days
Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence
Proportion of patients, requiring systemic treatment for bacterial, viral and fungal disease
Time frame: 100 days
Incidence of acute GVHD grade II-IV
Cumulative incidence of patients with acute GVHD II-IV grade
Time frame: 180 days
Incidence of moderate and severe chronic GVHD
Cumulative incidence of patients with moderate and severe chronic GVHD according to MAGIC 2018 criteria
Time frame: 2 years
Non-relapse mortality analysis
Cumulative incidence of patients with mortality without hematological relapse of malignancy
Time frame: 2 years
Relapse rate analysis
Cumulative incidence of patients with relapse
Time frame: 2 years
Event-free survival analysis
Kaplan-Meier estimate of death or relapse
Time frame: 2 years
GVHD-event-free survival analysis
Kaplan-Meier estimate of death, grade III-IV acute GVHD, severe chronic GVHD or relapse
Time frame: 2 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.