The purpose of this study is to evaluate the safety and efficiency of personalized targeted therapy in combination with high-dose chemotherapy as part of a preparative regimen before T-depleted allogeneic hematopoietic stem cell transplantation in children with chemoresistant acute leukemias
The outcome of hematopoietic stem cell transplantation (HSCT) in a cohort of children with chemorefractory leukemia is poor. The incidence of relapse exceeds 50% and survival varies from 10 to 40%. Additional attempts at remission induction with various combinations of chemotherapy are unlikely to improve the outcome and will contribute to toxicity. The hypothesis of the study is that personalized targeted therapy combined with high-dose chemotherapy may improve the outcome of allogeneic HSCT in a cohort of pediatric patients with refractory leukemia. Bcl-2, CD38, CD184 were chosen as potential targets due to frequent expression in pediatric acute leukemias, availability of marketed targeted therapies venetoclax, daratumumab and prelixafor, and expected non-overlapping toxicity profile of these agents and the conditioning regimen.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
25
Preparative chemotherapy before allogeneic HSCT * Fludarabin * Cytarabine * Venetoclax * Daratumomab * Vecanoid Condition * treosulfan * fludarabine * thiophosphomide * Venetoclax * Plerixafor GVHD prophylaxis * abatacept * tocilizumab * rituximab * HSCT from the haploidentical donor, ex vivo depleted of alpha/beta T lymphocytes
Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology
Moscow, Russia
RECRUITINGcumulative incidence of neutrophil and platelets engraftment at day +30 after HSCT
Time frame: 30 days after HSCT
Overall response rate
Proportion of patients with hematologic remission at time points
Time frame: 30 days after HSCT
Partial response rate
Proportion of patients with MRD negativity at time points
Time frame: 30 days after HSCT
Rate of toxicity stage > 3 according to CTCAE 5.0
Proportion of patients with allergic/ anaphylaxis reaction toxicity stage \> 3 according to CTCAE 5.0
Time frame: 40 days after first drug administration
cumulative incidence of transplant-related mortality
Time frame: 100 days after HSCT
Rate of expression of target molecule on blast cells
Proportion of patients with target molecule on blast cells: CD38 and/or CD 184 and/or Bcl2
Time frame: 1 week before first drug administration
cumulative incidence of acute GVHD grade II-IV
Time frame: 120 days after HSCT
cumulative incidence of chronic GvHD
Time frame: 1 year after HSCT
Rate of immune recovery at day 30
Proportion of patients with early immune recovery: T-cell, NK- cell, B-cell \>determined numbers
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Time frame: 30
overall survival
Time frame: 1 year after HSCT
event-free survival
Time frame: 1 year after HSCT