Immunotherapy With ex Vivo Expanded Haploidentical Natural Killer Cells for Children/Young Adults With AML

Study Overview
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Brief Summary
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The purpose of this study is to estimate the efficacy of immunotherapy with ex vivo expanded haploidentical NK cells for children/young adults with primary high risk or refractory AML and relapsed AML.

Detailed Description
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Immunotherapy with NK cells may improve the treatment results in AML. For better efficiency high cell doses or several infusions of NK cells are required. For this purpose, donor NK cells are expanded in the presence of feeder K562-mbIL21-41BBL cell line. For patients with high-risk primary AML a cycle of immunotherapy includes chemotherapy (HD-ARA-C+IDA) followed by three doses of NK cells infusion. For patients with refractory/relapsed AML a cycle of immunotherapy includes chemotherapy (FLAG - fludarabine, cytarabine, G-CSF) followed by three doses of NK cells infusion. A 2nd cycle of therapy may be administered if a recipient continues to meet the eligibility criteria.

Official Title
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Immunotherapy With ex Vivo Expanded Haploidentical Natural Killer Cells for Children/Young Adults With High-risk, Refractory or Relapsed AML

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Biological: NK cell infusions


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients: primary high risk AML primary refractory AML relapsed AML Karnofsky or Lansky performance scale greater or equal to 70 written informed consent Donors: haploidentical family donor 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 positive serology for HIV, hepatitis B or C

Ages Eligible for Study
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Minimum Age: 6 Months
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: expanded haploidentical NK cell immunotherapy<br>After a cycle of chemotherapy a patient receive three intravenous infusions of expanded haploidentical NK cells. | Biological: NK cell infusions<br>* Three doses of expanded haploidentical NK cells (30-100 x 10^6 cells /kg).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) (PR+ MLFS+CRi +CR) | The proportion of patients with complete remission (CR), CR with incomplete hematologic recovery (CRi), morphologic leukemia-free state (MLFS), and partial remission (PR) as measured by response criteria definitions for acute myeloid leukemia. | 30 days after every a course of NK immunotherapy | 
| Leukemia-free survival (LFS) | Time from achievement of CR/CRi/MLFS to the time of relapse, death in remission, or last follow-up. | 1 year | 
| Overall survival (OS) | The proportion of patients with overall survival | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of persistence of infused NK cells | Days of persistence of donor NK cells | 21 days after the first 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) after NK infusions. | 30 days after the first infusion | 

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