Randomised trial to determine the efficacy of immunotherapy with natural killer cells in high-risk acute myeloid leukemia

Phase 1

• Conditions: ewly diagnosed high-risk AML other than acute promyelocytic leukemia, =20% blasts; MedDRA version: 17.0Level: LLTClassification code 10000886Term: Acute myeloid leukemiaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2013-003421-28-DE
• Lead Sponsor: Technische Universität Dreden

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-01-03
• Last Update Posted: 12 November 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 56

Inclusion Criteria

• Newly diagnosed AML other than acute promyelocytic leukemia (APL) according to WHO criteria, i.e. bone marrow aspirate or biopsy must have contained =20% blasts
• 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 (either two induction cycles or one induction + one consolidation cycle)
• Study inclusion (experimental or control intervention) latest 56 days after preceding chemotherapy
• Reconstitution of peripheral blood leukocytes following chemotherapy (total leukocytes >1.5 GPT/l; neutrophil granulocytes >0.5 GPT/l)
• No available HLA-matched (= 9 of 10 HLA-alleles) stem cell donor or unfit for allogeneic hematopoietic stem cell transplantation
• Available haploidentical family donor, willing and fit for NK cell donation
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 56
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 56

Exclusion Criteria

• AML with favorable risk cytogenetic features, i.e. t(15;17) or PML-RAR alpha transcript or t(8;21) or RUNX1 transcript or inv(16) or CBFa transcript
• AML with t(9;11)(p22;q23)
• AML with intermediate risk cytogenetic features, i.e. no high-risk cytogenetic features as defined in inclusion criteria and no favorable cyto-genetic features as defined in exclusion criteria, FLT3-ITD ratio =0.8
• Persistent aplasia following preceding chemotherapy
• Relapsed or refractory AML
• Available HLA-matched (=9 of 10 HLA-alleles) stem cell donor and patient fit for allogeneic stem cell transplantation
• Age <60 years
• Known pre-existing autoimmune diseases
• Any severe concomitant condition which makes it undesirable for the patient to participate in the study (e.g. end stage irreversible multi organ failure, HIV infection, uncontrolled active infections >°2 )
• Any condition which could jeorpadize compliance of the protocol
• Participation in another clinical trial (investigational drug therapy outside of this trial) during or within 4 weeks before study entry

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare the efficacy of haploidentical NK-cell based consolidation with standard cytarabine based consolidation in elderly patients suffering from AML with high risk of fatal relapse and no option for allogeneic stem cell transplantation (SCT). ;Secondary Objective: - To compare the time to relapse (TTR), the cumulative incidence of relapse (CIR) and relapse-free survival (RFS) between the two study groups<br>- To investigate the yield and purity of NK cells (CD3-CD56+) after CD3 de-pletion and CD56 enrichment<br>- To investigate patients NC cell recovery, NK cell chimerism, NK phenotype and functional capacity of NK cells at various time points after infusion<br>- To compare tolerability and safety of the two interventions;Primary end point(s): 2-year overall survival;Timepoint(s) of evaluation of this end point: 2-year after study inclusion

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • Time to relapse (TTR), cumulative incidence of relapse (CIR),<br>• Relapse-free survival (RFS), <br>• Yield and purity of NK cells (CD3-CD56+) after CD3 depletion and CD56 enrichment, <br>• Patient NK cell recovery <br>• NK cell chimerism <br>• NK phenotype s <br>• Clinical performance (ECOG score)<br>• Incidence and severity of GVHD<br>• Incidence of AEs and SAEs;Timepoint(s) of evaluation of this end point: up to 2 years from study inclusion