Safety of Expanded Haploidentical Natural Killer Cells for Leukemia

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Leukemia, Acute Myeloid, Leukemia, Acute Lymphoblastic

Intervention / Treatment
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* Biological: Expanded Haploidentical Natural Killer cells
* Drug: IL-2


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NK cells + IL-2<br>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<br>* One dose (from 20x to >100x 10^6 /kg) of expanded haploidentical NK cells<br>Drug: IL-2<br>* 6 doses of IL-2 (1 × 10^6 units/m2) from -1 day every other day.<br>* Other names: Ronkoleukinum;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events | Adverse events will be graded according to the CTCAE v4.0 | 1 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days of persistence of adoptively-transferred haploidentical NK cells | Analysis of donor chimerism at +2, 6, 10, 14, 21, 28 days after NK infusion. | 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. | 1 months post infusion | 
| Median time to leukocytes and platelets recovery | Days of platelets (>50x10^9/L) and leukocytes (>1x10^9/L) recovery. | 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. | 1 months post infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunotherapy, Natural killer cells