Safety of Expanded Haploidentical Natural Killer Cells for Leukemia

Phase 1

Completed

• Conditions: Leukemia, Acute Myeloid; Leukemia, Acute Lymphoblastic
• Interventions: Biological: Expanded Haploidentical Natural Killer cells; Drug: IL-2

• Registration Number: NCT04327037
• Lead Sponsor: Belarusian Research Center for Pediatric Oncology, Hematology and Immunology

Brief Summary

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

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 Timeline

• Study Start: 2019-01-02
• Study First Submitted: 2020-03-18
• Study First Submitted QC: 2020-03-27
• Study First Posted: 2020-03-30
• Primary Completion: 2021-06-06
• Study Completion: 2021-06-30
• Status Verified: 2022-02
• Last Update Submitted: 2022-02-28
• Last Update Posted: 2022-03-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
NK cells + IL-2	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.
NK cells + IL-2	Expanded Haploidentical Natural Killer cells	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.

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment-Emergent Adverse Events	1 months	Adverse events will be graded according to the CTCAE v4.0

Secondary Outcome Measures

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

Trial Locations

Locations (1)

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