Expanded Haploidentical Natural Killer Cells as Consolidation Strategy 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 as consolidation therapy for children/young adults with intermediate risk 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. The cycle of immunotherapy includes chemotherapy (cyclophosphamide, fludarabine) followed by two doses of NK cells infusion.

Official Title
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Immunotherapy With ex Vivo Expanded Haploidentical Natural Killer Cells as Consolidation Strategy for Children/Young Adults With AML

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Biological: Expanded haploidentical NK cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients: primary intermediate risk AML in molecular complete remission; primary high risk AML in molecular complete remission awaiting unrelated HSCT; 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: 21 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 lymphodepleting chemotherapy a patient receive two intravenous infusions of expanded haploidentical NK cells. | Biological: Expanded haploidentical NK cells<br>* Two 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 |
| --- | --- | --- |
| Relapse-free survival (RFS) | Time from achievement of CR to the time of relapse or death from any cause. | 2 years | 
| Overall survival (OS) | The proportion of patients with overall survival | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Persistence of donor 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. | 28 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