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

NCT ID: NCT04000698

Last Updated: 2020-11-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

25 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-15

Study Completion Date

2022-12-31

Brief Summary

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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

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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.

Conditions

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Refractory Acute Myeloid Leukemia Refractory Acute Lymphoblastic Leukemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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intervention/treatment

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

Group Type EXPERIMENTAL

Preparative regimen

Intervention Type DRUG

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

Interventions

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Preparative regimen

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

Intervention Type DRUG

Eligibility Criteria

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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

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Federal Research Institute of Pediatric Hematology, Oncology and Immunology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology

Moscow, , Russia

Site Status RECRUITING

Countries

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Russia

Central Contacts

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Larisa Shelikhova

Role: CONTACT

Phone: 84956647078

Email: [email protected]

Zhanna Shekhovtsova

Role: CONTACT

Phone: 84956647078

Email: [email protected]

Facility Contacts

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Zhanna Shekhovtsova, MD

Role: primary

Eugene Pashanov, PhD

Role: backup

Other Identifiers

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NCPHOI-2018-08

Identifier Type: -

Identifier Source: org_study_id