Safety of Expanded Haploidentical Natural Killer Cells for Leukemia

Belarusian Research Center for Pediatric Oncology, Hematology and Immunology10 enrolled

Overview

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

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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Leukemia, Acute Myeloid Leukemia, Acute Lymphoblastic

Interventions

Expanded Haploidentical Natural Killer cellsBIOLOGICAL

One dose (from 20x to \>100x 10\^6 /kg) of expanded haploidentical NK cells

IL-2DRUG

6 doses of IL-2 (1 × 10\^6 units/m2) from -1 day every other day.

Eligibility

Sex: ALLMin age: 1 YearMax age: 30 Years

Medical Language ↔ Plain English

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.

Locations (1)

Belarussian Research Center for Pediatric Oncology, Hematology and Immunology

Minsk, Minsk Oblast, Belarus

Outcomes

Primary Outcomes

Incidence of Treatment-Emergent Adverse Events

Adverse events will be graded according to the CTCAE v4.0

Time frame: 1 months

Secondary Outcomes

Days of persistence of adoptively-transferred haploidentical NK cells

Analysis of donor chimerism at +2, 6, 10, 14, 21, 28 days after NK infusion.

Time frame: 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.

Time frame: 1 months post infusion

Median time to leukocytes and platelets recovery

Days of platelets (\>50x10\^9/L) and leukocytes (\>1x10\^9/L) recovery.

Time frame: 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.

Time frame: 1 months post infusion

Data from ClinicalTrials.gov

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