Personalized Targeted Preparative Regimen Before T-depleted Allogeneic HSCT in Children With Chemoresistent Acute Leukemias
A Phase I-II Pilot Clinical Trial of Safety and Efficacy of Personalized Targeted Preparative Regimen With Allogeneic TcRαβ/CD19-depleted Hematopoietic Stem Cell Transplantation and Posttransplant Donor T- Cells Infusion in Children With Chemoresistаnt Acute Leukemia.
1 other identifier
interventional
25
1 country
1
Brief Summary
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started Oct 2019
Typical duration for phase_3
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 25, 2019
CompletedFirst Posted
Study publicly available on registry
June 27, 2019
CompletedStudy Start
First participant enrolled
October 15, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2022
CompletedNovember 20, 2020
November 1, 2020
2.7 years
June 25, 2019
November 19, 2020
Conditions
Outcome Measures
Primary Outcomes (5)
cumulative incidence of neutrophil and platelets engraftment at day +30 after HSCT
30 days after HSCT
Overall response rate
Proportion of patients with hematologic remission at time points
30 days after HSCT
Partial response rate
Proportion of patients with MRD negativity at time points
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
40 days after first drug administration
cumulative incidence of transplant-related mortality
100 days after HSCT
Secondary Outcomes (6)
Rate of expression of target molecule on blast cells
1 week before first drug administration
cumulative incidence of acute GVHD grade II-IV
120 days after HSCT
cumulative incidence of chronic GvHD
1 year after HSCT
Rate of immune recovery at day 30
30
overall survival
1 year after HSCT
- +1 more secondary outcomes
Study Arms (1)
intervention/treatment
EXPERIMENTALPreparative chemotherapy before allogeneic HSCT * Fludarabin * Cytarabine * Venetoclax * Daratumomab * Vecanoid * treosulfan * fludarabine * thiophosphomide * Venetoclax * Plerixafor * abatacept * tocilizumab * rituximab * HSCT from the haploidentical donor, ex vivo depleted of alpha/beta T lymphocytes
Interventions
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
Eligibility Criteria
You may qualify if:
- Ability to give informed consent (for patients \> 14 years old). For subjects \< 18 years old their legal guardian must give informed consent
- Disease stage
- Acute myeloid leukemia (AML), relapsed or refractory, failure to achieve hematologic remission after at least to courses of intensive chemotherapy, including at least one course with high-dose AraC and fludarabine
- Acute lymphoblastic leukemia (ALL), relapsed or refractory, failure to achieve hematologic remission after at least two high-dose therapy blocks
- Patient eligible for current hematopoietic stem cell transplantation protocol
- The BCL-2 expression must be detected on greater than 30% of tumor cells (AML and ALL) by flow cytometry
- CD38 expression must be detected on greater than 30% of tumor cells (AML and ALL) by flow cytometry
- CD184
- Patients must have measurable or evaluable disease at the time of enrollment, which may include any evidence of disease including minimal residual disease detected by flow cytometry, cytogenetics, or polymerase chain reaction (PCR) analysis.
- Patient Clinical Performance Status: Karnofsky \>50% or Lansky \>50%
- Patient Life Expectancy \>12 weeks
- Patients who agree to long-term follow up for up to 5 years
You may not qualify if:
- Age \>25 years
- Patients with uncontrolled infections
- Clearance of creatinine \< 70 ml/min
- Cardiac ejection fraction \< 40%
- Patients who can perform pulmonary function tests will be excluded if they have a diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) of \< 50% predicted; patients who are unable to perform pulmonary function tests will be excluded if the oxygen (O2) saturation is \< 92% on room air
- Patients who have liver function test (LFTs) (including total bilirubin, aspartate aminotransferase \[AST\] and alanine aminotransferase \[ALT\]) \>= twice the upper limit of normal
- Karnofsky/Lansky Scale \<70%
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology
Moscow, 117997, Russia
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 25, 2019
First Posted
June 27, 2019
Study Start
October 15, 2019
Primary Completion
July 1, 2022
Study Completion
December 1, 2022
Last Updated
November 20, 2020
Record last verified: 2020-11