Randomised Controlled Phase-2 Trial to Determine the Efficacy of Adoptive Immunotherapy With NK Cells in High-risk AML

Study Overview
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Brief Summary
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The trial investigates the efficacy of adoptive immunotherapy with haploidentical natural killer cells compared to standard chemotherapy (after first complete remission) in patients with a high-risk acute myeloid leukemia being older than 65 years of age and not eligible for allogeneic transplantation

Detailed Description
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Randomised controlled phase-2 trial to determine the efficacy of adoptive immunotherapy with haploidentical natural killer cells in high-risk acute myeloid leukemia

Official Title
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Randomised Controlled Phase-2 Trial to Determine the Efficacy of Adoptive Immunotherapy With Haploidentical Natural Killer Cells in High-risk Acute Myeloid Leukemia

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Biological: NK cells
* Drug: Cytarabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed AML other than acute promyelocytic leukemia (APL) according to WHO criteria In AML defined by cytogenetic aberrations the proportion of blasts may be <20% Age ≥60 years Clinical performance corresponding to ECOG score 0-2 High-risk karyotype <5% myeloblasts in bone marrow ≥21 days after beginning of most recent chemotherapy maximal two preceding chemotherapy cycles Potentially available haploidentical family donor (child/ sibling), willing and fit for NK cell donation Exclusion Criteria: AML with favorable or intermediate risk cytogenetic features Persistent aplasia following preceding chemotherapy Relapsed or refractory AML Known pre-existing autoimmune diseases Any severe concomitant condition which makes it undesirable for the patient to participate in the study Any condition which could jeorpadize compliance of the protocol Participation in another clinical trial during or within 4 weeks before study entry

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 99 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NK cells<br>Infusion of haploidentical NK cells after immunosuppression with cyclophosphamide and fludarabine, followed by immunostimulatory treatment with interleukin-2 | Biological: NK cells<br> <br> * Other names: donors;|
| Active Comparator: Control Intervention<br>1 cycle of consolidation chemotherapy with high-dose cytarabine | Drug: Cytarabine<br>* 1 cycle of consolidation chemotherapy with high-dose cytarabine<br>* Other names: chemotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year overall survival | measure time of survival of each patiente up to 2 years after study inclusion | 2 years after study inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to relapse | evaluate time to relapse for 2 years after study inclusion for each patient; calculate cumulative incidence of relapse | 2 years after study inclusion | 
| Relapse-free survival |  | 2 years after study inclusion | 
| Yield and purity of NK cells (CD3-CD56+) after CD3 depletion and CD56 enrichment |  | timepoint of application of NK cells | 
| NK cell analysis |  | 2 years after study inclusion | 
| Clinical performance (ECOG score) |  | 2 years after study inclusion | 
| Incidence and severity of GVHD |  | 6 months after start of treatment | 
| Incidence of (S)AEs |  | 5 weeks after start of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML, high-risk AML, acute myeloid leukemia, NK cells, haploidentical natural killer cells, immunotherapy