Safety of Expanded Haploidentical Natural Killer Cells for Leukemia

Sponsor

Belarusian Research Center for Pediatric Oncology, Hematology and Immunology (Other)

Overall Status

Completed

CT.gov ID

NCT04327037

Collaborator

(none)

Enrollment

Location

Arm

29.9

Actual Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Acute Myeloid Leukemia, Acute Lymphoblastic	Biological: Expanded Haploidentical Natural Killer cells Drug: IL-2	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 2, 2019

Actual Primary Completion Date :

Jun 6, 2021

Actual Study Completion Date :

Jun 30, 2021

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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.
Median time to leukocytes and platelets recovery [2 months post infusion]
Days of platelets (>50x10^9/L) and leukocytes (>1x10^9/L) recovery.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 30 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Belarussian Research Center for Pediatric Oncology, Hematology and Immunology	Minsk	Minsk Region	Belarus	223053

Sponsors and Collaborators

Belarusian Research Center for Pediatric Oncology, Hematology and Immunology

Investigators

Principal Investigator: Olga Aleinikova, Belarussian Research Center for Pediatric Oncology, Hematology and Immunology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Belarusian Research Center for Pediatric Oncology, Hematology and Immunology

ClinicalTrials.gov Identifier:

NCT04327037

Other Study ID Numbers:

BelarusianPediatric_NK_Pilot

First Posted:

Mar 30, 2020

Last Update Posted:

Mar 2, 2022

Last Verified:

Feb 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Belarusian Research Center for Pediatric Oncology, Hematology and Immunology

Immunotherapy

Natural killer cells

Additional relevant MeSH terms:

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Myeloid, Acute

Acute Disease

Study Results

No Results Posted as of Mar 2, 2022