Back to resultsRandomised Controlled Phase-2 Trial to Determine the Efficacy of Adoptive Immunotherapy With NK Cells in High-risk AML (HINKL)
Primary Purpose
Acute Myeloid Leukemia
Status
Terminated
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
NK cells
Cytarabine
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring AML, high-risk AML, acute myeloid leukemia, NK cells, haploidentical natural killer cells, immunotherapy
Eligibility Criteria
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
Sites / Locations
- Klinikum Bayreuth
- Klinikum Chemnitz
- Universitätsklinikum Dresden
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
NK cells
Control Intervention
Arm Description
Infusion of haploidentical NK cells after immunosuppression with cyclophosphamide and fludarabine, followed by immunostimulatory treatment with interleukin-2
1 cycle of consolidation chemotherapy with high-dose cytarabine
Outcomes
Primary Outcome Measures
2-year overall survival
measure time of survival of each patiente up to 2 years after study inclusion
Secondary Outcome Measures
Time to relapse
evaluate time to relapse for 2 years after study inclusion for each patient; calculate cumulative incidence of relapse
Relapse-free survival
Yield and purity of NK cells (CD3-CD56+) after CD3 depletion and CD56 enrichment
NK cell analysis
Clinical performance (ECOG score)
Incidence and severity of GVHD
Incidence of (S)AEs
Full Information
NCT ID
NCT02229266
First Posted
August 28, 2014
Last Updated
August 10, 2021
Sponsor
Technische Universität Dresden
Collaborators
German Research Foundation
1. Study Identification
Unique Protocol Identification Number
NCT02229266
Brief Title
Randomised Controlled Phase-2 Trial to Determine the Efficacy of Adoptive Immunotherapy With NK Cells in High-risk AML
Acronym
HINKL
Official Title
Randomised Controlled Phase-2 Trial to Determine the Efficacy of Adoptive Immunotherapy With Haploidentical Natural Killer Cells in High-risk Acute Myeloid Leukemia
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Terminated
Why Stopped
low recruitment rate
Study Start Date
September 2015 (undefined)
Primary Completion Date
April 22, 2017 (Actual)
Study Completion Date
April 22, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Technische Universität Dresden
Collaborators
German Research Foundation
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
Randomised controlled phase-2 trial to determine the efficacy of adoptive immunotherapy with haploidentical natural killer cells in high-risk acute myeloid leukemia
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia
Keywords
AML, high-risk AML, acute myeloid leukemia, NK cells, haploidentical natural killer cells, immunotherapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1 (Actual)
8. Arms, Groups, and Interventions
Arm Title
NK cells
Arm Type
Experimental
Arm Description
Infusion of haploidentical NK cells after immunosuppression with cyclophosphamide and fludarabine, followed by immunostimulatory treatment with interleukin-2
Arm Title
Control Intervention
Arm Type
Active Comparator
Arm Description
1 cycle of consolidation chemotherapy with high-dose cytarabine
Intervention Type
Biological
Intervention Name(s)
NK cells
Other Intervention Name(s)
CD3-negative/ CD56-positive NK cells from HLA-haploidentical family, donors
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Other Intervention Name(s)
chemotherapy
Intervention Description
1 cycle of consolidation chemotherapy with high-dose cytarabine
Primary Outcome Measure Information:
Title
2-year overall survival
Description
measure time of survival of each patiente up to 2 years after study inclusion
Time Frame
2 years after study inclusion
Secondary Outcome Measure Information:
Title
Time to relapse
Description
evaluate time to relapse for 2 years after study inclusion for each patient; calculate cumulative incidence of relapse
Time Frame
2 years after study inclusion
Title
Relapse-free survival
Time Frame
2 years after study inclusion
Title
Yield and purity of NK cells (CD3-CD56+) after CD3 depletion and CD56 enrichment
Time Frame
timepoint of application of NK cells
Title
NK cell analysis
Time Frame
2 years after study inclusion
Title
Clinical performance (ECOG score)
Time Frame
2 years after study inclusion
Title
Incidence and severity of GVHD
Time Frame
6 months after start of treatment
Title
Incidence of (S)AEs
Time Frame
5 weeks after start of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Martin Bornhäuser, Prof. Dr. med.
Organizational Affiliation
Universitätsklinikum Dresden
Official's Role
Principal Investigator
Facility Information:
Facility Name
Klinikum Bayreuth
City
Bayreuth
Country
Germany
Facility Name
Klinikum Chemnitz
City
Chemnitz
Country
Germany
Facility Name
Universitätsklinikum Dresden
City
Dresden
Country
Germany
12. IPD Sharing Statement
Links:
URL
http://www.sal-aml.org
Description
Study Alliance Leukemia
URL
http://www.uniklinikum-dresden.de/das-klinikum/kliniken-polikliniken-institute/mk1
Description
Universitätsklinikum Dresden, Medizinische Klinik I
Learn more about this trial
Randomised Controlled Phase-2 Trial to Determine the Efficacy of Adoptive Immunotherapy With NK Cells in High-risk AML
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