Description:
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
Title
- Brief Title: Personalized Targeted Preparative Regimen Before T-depleted Allogeneic HSCT in Children With Chemoresistent Acute Leukemias
- Official Title: 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.
Clinical Trial IDs
- ORG STUDY ID:
NCPHOI-2018-08
- NCT ID:
NCT04000698
Conditions
- Refractory Acute Myeloid Leukemia
- Refractory Acute Lymphoblastic Leukemia
Interventions
Drug | Synonyms | Arms |
---|
Preparative regimen | | intervention/treatment |
Purpose
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
Detailed Description
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.
Trial Arms
Name | Type | Description | Interventions |
---|
intervention/treatment | Experimental | Preparative 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 | |
Eligibility Criteria
Inclusion Criteria:
1. Ability to give informed consent (for patients > 14 years old). For subjects < 18
years old their legal guardian must give informed consent
2. 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
3. Patient eligible for current hematopoietic stem cell transplantation protocol
4. The BCL-2 expression must be detected on greater than 30% of tumor cells (AML and ALL)
by flow cytometry
5. CD38 expression must be detected on greater than 30% of tumor cells (AML and ALL) by
flow cytometry
6. CD184
7. 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.
8. Patient Clinical Performance Status: Karnofsky >50% or Lansky >50%
9. Patient Life Expectancy >12 weeks
10. Patients who agree to long-term follow up for up to 5 years
Exclusion Criteria:
- 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%
Maximum Eligible Age: | 25 Years |
Minimum Eligible Age: | N/A |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | cumulative incidence of neutrophil and platelets engraftment at day +30 after HSCT |
Time Frame: | 30 days after HSCT |
Safety Issue: | |
Description: | Proportion of patients with hematologic remission at time points |
Secondary Outcome Measures
Measure: | Rate of expression of target molecule on blast cells |
Time Frame: | 1 week before first drug administration |
Safety Issue: | |
Description: | Proportion of patients with target molecule on blast cells: CD38 and/or CD 184 and/or Bcl2 |
Measure: | cumulative incidence of acute GVHD grade II-IV |
Time Frame: | 120 days after HSCT |
Safety Issue: | |
Description: | |
Measure: | cumulative incidence of chronic GvHD |
Time Frame: | 1 year after HSCT |
Safety Issue: | |
Description: | |
Measure: | Rate of immune recovery at day 30 |
Time Frame: | 30 |
Safety Issue: | |
Description: | Proportion of patients with early immune recovery: T-cell, NK- cell, B-cell >determined numbers |
Measure: | overall survival |
Time Frame: | 1 year after HSCT |
Safety Issue: | |
Description: | |
Measure: | event-free survival |
Time Frame: | 1 year after HSCT |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Federal Research Institute of Pediatric Hematology, Oncology and Immunology |
Last Updated
November 20, 2020