Leukemia, Acute Lymphoblastic, Leukemia, Acute Myeloid
Conditions
Keywords
Immunotherapy, Natural killer cells
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.
Interventions
BIOLOGICALExpanded Haploidentical Natural Killer cells
One dose (from 20x to \>100x 10\^6 /kg) of expanded haploidentical NK cells
DRUGIL-2
6 doses of IL-2 (1 × 10\^6 units/m2) from -1 day every other day.
Sponsors
Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 30 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events | 1 months | Adverse events will be graded according to the CTCAE v4.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Belarus
Outcome results
None listed