Immunotherapy With ex Vivo Expanded Haploidentical Natural Killer Cells for Children/Young Adults With AML

Phase 1

Recruiting

• Conditions: Acute Myeloid Leukemia
• Interventions: Biological: NK cell infusions

• Registration Number: NCT05272293
• Lead Sponsor: Belarusian Research Center for Pediatric Oncology, Hematology and Immunology

Brief Summary

The purpose of this study is to estimate the efficacy of immunotherapy with ex vivo expanded haploidentical NK cells for children/young adults with primary high risk or refractory AML and relapsed AML.

Detailed Description

Immunotherapy with NK cells may improve the treatment results in AML. For better efficiency high cell doses or several infusions of NK cells are required. For this purpose, donor NK cells are expanded in the presence of feeder K562-mbIL21-41BBL cell line.

For patients with high-risk primary AML a cycle of immunotherapy includes chemotherapy (HD-ARA-C+IDA) followed by three doses of NK cells infusion.

For patients with refractory/relapsed AML a cycle of immunotherapy includes chemotherapy (FLAG - fludarabine, cytarabine, G-CSF) followed by three doses of NK cells infusion.

A 2nd cycle of therapy may be administered if a recipient continues to meet the eligibility criteria.

Study Timeline

• Study Start: 2021-11-01
• Study First Submitted: 2022-02-28
• Study First Submitted QC: 2022-02-28
• Study First Posted: 2022-03-09
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-27
• Last Update Posted: 2024-08-28
• Primary Completion: 2025-12
• Study Completion: 2026-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

Patients:

• primary high risk AML
• primary refractory AML
• relapsed AML
• Karnofsky or Lansky performance scale greater or equal to 70
• written informed consent

Donors:

• haploidentical family donor
• donor suitable for cell donation and apheresis according to standard criteria
• written informed consent

Exclusion Criteria

Patients:

• uncontrolled infection
• severe hepatic dysfunction: SGOT or SCPT >=5x upper limit of normal for age
• positive serology for human immunodeficiency virus (HIV)

Donors:

• pregnancy
• positive serology for HIV, hepatitis B or C

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
expanded haploidentical NK cell immunotherapy	NK cell infusions	After a cycle of chemotherapy a patient receive three intravenous infusions of expanded haploidentical NK cells.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) (PR+ MLFS+CRi +CR)	30 days after every a course of NK immunotherapy	The proportion of patients with complete remission (CR), CR with incomplete hematologic recovery (CRi), morphologic leukemia-free state (MLFS), and partial remission (PR) as measured by response criteria definitions for acute myeloid leukemia.
Overall survival (OS)	1 year	The proportion of patients with overall survival
Leukemia-free survival (LFS)	1 year	Time from achievement of CR/CRi/MLFS to the time of relapse, death in remission, or last follow-up.

Secondary Outcome Measures

Name	Time	Method
Duration of persistence of infused NK cells	21 days after the first infusion	Days of persistence of donor NK cells
Number of T, B, NK, activated T and NK cells after immunotherapy	30 days after the first infusion	Analysis of T, B, NK, activated T and NK cells numbers (cells/microL) after NK infusions.

Trial Locations

Locations (1)

Belarussian Research Center for Pediatric Oncology, Hematology and Immunology; 🇧🇾 Minsk, Minsk Region, Belarus