Clinical Trials /

Personalized Targeted Preparative Regimen Before T-depleted Allogeneic HSCT in Children With Chemoresistent Acute Leukemias

NCT04000698

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

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
Recruiting Status:

Not yet recruiting

Phase:

Phase 3

Trial Eligibility

Document

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

DrugSynonymsArms
Preparative regimenintervention/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

NameTypeDescriptionInterventions
intervention/treatmentExperimentalPreparative 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
  • Preparative regimen

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:Not yet recruiting
Lead Sponsor:Federal Research Institute of Pediatric Hematology, Oncology and Immunology

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