Safety of Expanded Haploidentical Natural Killer Cells for Leukemia

Belarusian Research Center for Pediatric Oncology, Hematology and Immunology

Status and phase: Completed; Phase 1

Conditions: Leukemia, Acute Lymphoblastic; Leukemia, Acute Myeloid

Treatments: Drug: IL-2; Biological: Expanded Haploidentical Natural Killer cells

Study type: Interventional

Funder types: Other

Identifiers

NCT04327037

BelarusianPediatric_NK_Pilot

Details and patient eligibility

About

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

Full 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.

Enrollment: 10 patients

Sex: All

Ages: 1 to 30 years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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10 participants in 1 patient group

NK cells + IL-2

Experimental group

Description:

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.

Treatment:

Biological: Expanded Haploidentical Natural Killer cells

Drug: IL-2