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

Immunotherapy With ex Vivo Expanded Haploidentical Natural Killer Cells for Children/Young Adults With High-risk, Refractory or Relapsed AML

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Biological: NK cell infusions

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 Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Tatsiana Shman, PhD; Phone Number: +375296341853; Email: shman@oncology.by
• Study Contact Backup: Name: Mariya Naumovich, MD; Phone Number: +375293563846; Email: mariyanaumovich@gmail.com

Study Locations

• Belarus
  • Minsk Region
    • Minsk, Minsk Region, Belarus, 223053
      • Recruiting
      • Belarussian Research Center for Pediatric Oncology, Hematology and Immunology
      • Contact: Tatsiana Shman; Phone Number: +37529 6341853; Email: shman@oncology.by
      • Contact: Mariya Naumovich; Phone Number: +375293563846; Email: mariyanaumovich@gmail.com
      • Principal Investigator: Olga Aleinikova, MD, Prof

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 30 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: expanded haploidentical NK cell immunotherapy; After a cycle of chemotherapy a patient receive three intravenous infusions of expanded haploidentical NK cells.	Biological: NK cell infusions; Three doses of expanded haploidentical NK cells (30-100 x 10^6 cells /kg).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) (PR+ MLFS+CRi +CR)	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.	30 days after every a course of NK immunotherapy
Leukemia-free survival (LFS)	Time from achievement of CR/CRi/MLFS to the time of relapse, death in remission, or last follow-up.	1 year
Overall survival (OS)	The proportion of patients with overall survival	1 year

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
• Investigators: Principal Investigator: Olga Aleinikova, MD, Prof, Belarussian Research Center for Pediatric Oncology, Hematology and Immunology

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2021
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: February 28, 2022
• First Submitted That Met QC Criteria: February 28, 2022
• First Posted (Actual): March 9, 2022

Study Record Updates

• Last Update Posted (Actual): August 28, 2024
• Last Update Submitted That Met QC Criteria: August 27, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Natural killer cells, immunotherapy
• Other Study ID Numbers: haploNK_ HR/R/R_AML

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No