Safety of Expanded Haploidentical Natural Killer Cells for Leukemia

Pilot Study of Immunotherapy With ex Vivo Expanded Haploidentical Natural Killer Cells for Leukemia

The purpose of this study is to estimate the safety of ex vivo expanded haploidentical natural killer (NK) cells for patients with leukemia.

Study Overview

• Status: Completed
• Conditions: Leukemia, Acute Lymphoblastic; Leukemia, Acute Myeloid
• Intervention / Treatment: Biological: Expanded Haploidentical Natural Killer cells; Drug: IL-2

Detailed Description

Immunotherapy with natural killer (NK) cells may improve the results of treatment for patients with cancer. However, for better efficiency high doses of NK cells are required. For this purpose, NK cells were expanded in the presence of feeder K562 cells gene-modified for expression 4-1BBL and membrane bound IL-21. In the result of expansion, large number of activated NK cells are obtained.

Protocol of immunotherapy includes conditioning (fludarabine + cyclophosphamide or any other protocol of chemotherapy) followed by expanded NK cells intravenous infusion. To sustain proliferation of donor NK cells in vivo patients receive 6 doses of Il-2 every second day. 10 patients will be enrolled in phase I to test different doses of NK cells: 20, 50, 70, 100 and >100 x 10^6/kg.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belarus
  • Minsk Region
    • Minsk, Minsk Region, Belarus, 223053
      • Belarussian Research Center for Pediatric Oncology, Hematology and Immunology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 30 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients:

• Relapsed acute myeloid or lymphoblastic leukemia
• Primary refractory myeloid or lymphoblastic leukemia
• Karnofsky or Lansky performance scale greater or equal to 70
• Written informed consent

Donor:

• Haploidentical family donor
• > 18 years old
• 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 or breast feeding
• 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: NK cells + IL-2; After cycle of chemotherapy patient receive one intravenous infusion of expanded haploidentical NK cells on day 0. On alternate days, 6 doses of subcutaneous IL-2 is administered with start on day -1.	Biological: Expanded Haploidentical Natural Killer cells; One dose (from 20x to >100x 10^6 /kg) of expanded haploidentical NK cells; Drug: IL-2; 6 doses of IL-2 (1 × 10^6 units/m2) from -1 day every other day.; Other Names: Ronkoleukinum

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events	Adverse events will be graded according to the CTCAE v4.0	1 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days of persistence of adoptively-transferred haploidentical NK cells	Analysis of donor chimerism at +2, 6, 10, 14, 21, 28 days after NK infusion.	1 months
Occurrence of disease response	Analysis of blast cells content in bone marrow by cytomorphology or detection of MRD level by flow/PCR before and after immunotherapy.	1 months post infusion
Median time to leukocytes and platelets recovery	Days of platelets (>50x10^9/L) and leukocytes (>1x10^9/L) recovery.	2 months post infusion
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) at +2, 6, 10, 14, 21, 28 days after NK infusion.	1 months post infusion

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2019
• Primary Completion (Actual): June 6, 2021
• Study Completion (Actual): June 30, 2021

Study Registration Dates

• First Submitted: March 18, 2020
• First Submitted That Met QC Criteria: March 27, 2020
• First Posted (Actual): March 30, 2020

Study Record Updates

• Last Update Posted (Actual): March 2, 2022
• Last Update Submitted That Met QC Criteria: February 28, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Immunotherapy; Natural killer cells
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Acute Disease
• Other Study ID Numbers: BelarusianPediatric_NK_Pilot

Drug and device information, study documents

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