Back to resultsMT2014-25: Haplo NK With SQ IL-15 in Adult Relapsed or Refractory AML Patients
Primary Purpose
Acute Myelogenous Leukemia
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
IL-15
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myelogenous Leukemia focused on measuring AML, Relapsed, Refractory
Eligibility Criteria
Inclusion Criteria (Recipient):
Meets ONE of the following disease criteria:
- Primary AML induction failure: no CR after 2 or more induction attempts
- Relapsed AML or Secondary AML (from MDS or treatment related): not in CR after 1 or more cycles of standard re-induction therapy
- AML relapsed > 2 months after transplant: No re-induction required, and no more than 1 re-induction cycle is allowed.
Relapsed AML for patients > 60 years of age the 1 cycle of standard chemotherapy is not required if either of the following criteria is met:
- Relapse within 6 months of last chemotherapy
- BM blast count < 30% within 10 days of starting protocol therapy
- Available related HLA-haploidentical donor (aged 14 to 75 years) by at least Class I serologic typing at the A&B locus
- Karnofsky Performance Status ≥ 60%
- Patients must have adequate organ within 14 days (28 days for pulmonary and cardiac) of study registration
- Able to be off prednisone or other immunosuppressive medications for at least 3 days prior to NK cell infusion (excluding preparative regimen pre-medications).
- Agrees to use contraception prior to study entry and for the duration of study participation.
Exclusion Criteria (Recipient):
- Bi-phenotypic acute leukemia.
- Transplant < 60 days prior to study enrollment.
- Active autoimmune disease.
- History of severe asthma
- Uncontrolled intercurrent illness
- New or progressive pulmonary infiltrates on screening chest x-ray or chest CT scan that has not been evaluated with bronchoscopy
- Pleural effusion large enough to be detectable on chest x-ray.
- Pregnant women
- History of HIV, active or chronic hepatitis B, hepatitis C or HTLV-I infection
- Known hypersensitivity to any of the study agents used
- Received investigational drugs within the 14 days of study registration.
- Known active CNS involvement.
Criteria For Initial Donor Selection:
- Related donors (sibling, parent, offspring, parent or offspring of an HLA identical sibling).
- 14-75 years of age.
- At least 40 kilogram body weight.
- In general good health as determined by the evaluating medical provider.
- HLA-haploidentical donor/recipient match by at least Class I serologic typing at the A&B locus.
- Not pregnant.
- Able and willing to undergo apheresis.
Sites / Locations
- Masonic Cancer Center at University of Minnesota
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Preparative Regimen and SubQ rHuIL-15
Arm Description
Preparative Regimen of Fludarabine and Cyclophosphamide IL-15 Activation of Donor NK Cells: IL-15 to Facilitate NK Cell Survival and Expansion
Outcomes
Primary Outcome Measures
< 5% Marrow Blast, no Circulating Peripheral Blasts and Neutrophil Count of > 1 x 10^9/L
Without platelet recovery
Secondary Outcome Measures
In Vivo Expansion (>100) of NK Cells (Defined at CD56+/CD3- Lymphocytes)
Proportion of Patients Experiencing Grade, 3, 4, and 5 Toxicities (Assessed by CTCAE v. 4)
Treatment Related Mortality
Number of Subjects Achieving Complete Response, Defined as in Vivo Donor Derived NK Cell Expansion of > 100 Donor Derived NK Cells.
Full Information
NCT ID
NCT02395822
First Posted
February 16, 2015
Last Updated
January 22, 2018
Sponsor
Masonic Cancer Center, University of Minnesota
1. Study Identification
Unique Protocol Identification Number
NCT02395822
Brief Title
MT2014-25: Haplo NK With SQ IL-15 in Adult Relapsed or Refractory AML Patients
Official Title
MT2014-25: Haploidentical Donor Natural Killer (NK) Cell Infusion With Subcutaneous Recombinant Human IL-15 (rhIL-15) in Adults With Refractory or Relapsed Acute Myelogenous Leukemia (AML)
Study Type
Interventional
2. Study Status
Record Verification Date
December 2017
Overall Recruitment Status
Completed
Study Start Date
October 1, 2015 (Actual)
Primary Completion Date
December 1, 2016 (Actual)
Study Completion Date
December 1, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Masonic Cancer Center, University of Minnesota
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A phase II trial of CD3/CD19 depleted, IL-15 activated, donor natural killer (NK) cells in adults and subcutaneous IL-15 given after a preparative regimen for the treatment of relapsed or refractory acute myelogenous leukemia (AML). The primary objective is to study the potential efficacy of NK cells and IL-15 to achieve complete remission while maintaining safety.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myelogenous Leukemia
Keywords
AML, Relapsed, Refractory
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
17 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Preparative Regimen and SubQ rHuIL-15
Arm Type
Experimental
Arm Description
Preparative Regimen of Fludarabine and Cyclophosphamide
IL-15 Activation of Donor NK Cells:
IL-15 to Facilitate NK Cell Survival and Expansion
Intervention Type
Biological
Intervention Name(s)
IL-15
Other Intervention Name(s)
Interleukin-15
Intervention Description
Preparative Regimen:
Fludarabine 25 mg/m2 x 5 days start day -6 Cyclophosphamide 60 mg/kg x 2 days on day -5 and -4 (if < 4 months from prior transplant, omit day -4 dose)
IL-15 Activated Donor NK Cells:
The apheresis product (collected day -1) will be enriched for NK cells with the large-scale CliniMacs® device (Miltenyi) by depletion of CD3+ cells to remove T-lymphocytes and depletion of CD19+ cells to remove B-lymphocytes. The NK cell enriched product will be activated by overnight incubation with10 ng/ml IL-15 under GMP conditions and infused on day 0.
IL-15 to Facilitate NK Cell Survival and Expansion:
IL-15 at 2 mcg/kg subcutaneously (SC) beginning day +1, once a day for 5 days followed by a 2 day rest, and then once a day for 5 days for 10 doses total
Primary Outcome Measure Information:
Title
< 5% Marrow Blast, no Circulating Peripheral Blasts and Neutrophil Count of > 1 x 10^9/L
Description
Without platelet recovery
Time Frame
Day 42 post NK cell infusion
Secondary Outcome Measure Information:
Title
In Vivo Expansion (>100) of NK Cells (Defined at CD56+/CD3- Lymphocytes)
Time Frame
Day 14 post NK cell infusion
Title
Proportion of Patients Experiencing Grade, 3, 4, and 5 Toxicities (Assessed by CTCAE v. 4)
Time Frame
Days 1-5 and Days 8-12, 24 hours after the last IL-15 dose, Day +28, Day +42
Title
Treatment Related Mortality
Time Frame
6 months post-therapy
Title
Number of Subjects Achieving Complete Response, Defined as in Vivo Donor Derived NK Cell Expansion of > 100 Donor Derived NK Cells.
Time Frame
Day 42 post NK cell infusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria (Recipient):
Meets ONE of the following disease criteria:
Primary AML induction failure: no CR after 2 or more induction attempts
Relapsed AML or Secondary AML (from MDS or treatment related): not in CR after 1 or more cycles of standard re-induction therapy
AML relapsed > 2 months after transplant: No re-induction required, and no more than 1 re-induction cycle is allowed.
Relapsed AML for patients > 60 years of age the 1 cycle of standard chemotherapy is not required if either of the following criteria is met:
Relapse within 6 months of last chemotherapy
BM blast count < 30% within 10 days of starting protocol therapy
Available related HLA-haploidentical donor (aged 14 to 75 years) by at least Class I serologic typing at the A&B locus
Karnofsky Performance Status ≥ 60%
Patients must have adequate organ within 14 days (28 days for pulmonary and cardiac) of study registration
Able to be off prednisone or other immunosuppressive medications for at least 3 days prior to NK cell infusion (excluding preparative regimen pre-medications).
Agrees to use contraception prior to study entry and for the duration of study participation.
Exclusion Criteria (Recipient):
Bi-phenotypic acute leukemia.
Transplant < 60 days prior to study enrollment.
Active autoimmune disease.
History of severe asthma
Uncontrolled intercurrent illness
New or progressive pulmonary infiltrates on screening chest x-ray or chest CT scan that has not been evaluated with bronchoscopy
Pleural effusion large enough to be detectable on chest x-ray.
Pregnant women
History of HIV, active or chronic hepatitis B, hepatitis C or HTLV-I infection
Known hypersensitivity to any of the study agents used
Received investigational drugs within the 14 days of study registration.
Known active CNS involvement.
Criteria For Initial Donor Selection:
Related donors (sibling, parent, offspring, parent or offspring of an HLA identical sibling).
14-75 years of age.
At least 40 kilogram body weight.
In general good health as determined by the evaluating medical provider.
HLA-haploidentical donor/recipient match by at least Class I serologic typing at the A&B locus.
Not pregnant.
Able and willing to undergo apheresis.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey Miller, MD
Organizational Affiliation
Masonic Cancer Center, University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
Masonic Cancer Center at University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
31266741
Citation
Cooley S, He F, Bachanova V, Vercellotti GM, DeFor TE, Curtsinger JM, Robertson P, Grzywacz B, Conlon KC, Waldmann TA, McKenna DH, Blazar BR, Weisdorf DJ, Miller JS. First-in-human trial of rhIL-15 and haploidentical natural killer cell therapy for advanced acute myeloid leukemia. Blood Adv. 2019 Jul 9;3(13):1970-1980. doi: 10.1182/bloodadvances.2018028332.
Results Reference
derived
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MT2014-25: Haplo NK With SQ IL-15 in Adult Relapsed or Refractory AML Patients
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