Clinical trial NCT04327037: Safety of Expanded Haploidentical Natural Killer Cells for Leukemia
Official title: Pilot Study of Immunotherapy With ex Vivo Expanded Haploidentical Natural Killer Cells for Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leukemia, Acute Myeloid
Leukemia, Acute Lymphoblastic
Keywords: Immunotherapy
Natural killer cells
Lead sponsor: Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
Sponsor class: OTHER
First posted: 2020-03-30
Enrollment: 10
Sex: ALL
Minimum age (years): 1
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 1 months
Secondary outcomes:
measure: Days of persistence of adoptively-transferred haploidentical NK cells
timeFrame: 1 months
measure: Occurrence of disease response
timeFrame: 1 months post infusion
measure: Median time to leukocytes and platelets recovery
timeFrame: 2 months post infusion
measure: Number of T, B, NK, activated T and NK cells after immunotherapy
timeFrame: 1 months post infusion
Other outcomes:
Locations:
city: Minsk
country: Belarus
facility: Belarussian Research Center for Pediatric Oncology, Hematology and Immunology
state: Minsk Region
Study officials:
affiliation: Belarussian Research Center for Pediatric Oncology, Hematology and Immunology
name: Olga Aleinikova
role: PRINCIPAL_INVESTIGATOR
References: