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MT2014-25: Haplo NK With SQ IL-15 in Adult Relapsed or Refractory AML Patients

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ClinicalTrials.gov Identifier: NCT02395822
Recruitment Status : Completed
First Posted : March 24, 2015
Results First Posted : January 10, 2018
Last Update Posted : February 20, 2018
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Acute Myelogenous Leukemia
Intervention Biological: IL-15
Enrollment 17
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Preparative Regimen and SubQ rHuIL-15
Hide Arm/Group Description

Preparative Regimen of Fludarabine and Cyclophosphamide

IL-15 Activation of Donor NK Cells:

IL-15 to Facilitate NK Cell Survival and Expansion

IL-15: 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

Period Title: Overall Study
Started 17
Completed 15
Not Completed 2
Reason Not Completed
Withdrawal by Subject             1
Death             1
Arm/Group Title Preparative Regimen and SubQ rHuIL-15
Hide Arm/Group Description

Preparative Regimen of Fludarabine and Cyclophosphamide

IL-15 Activation of Donor NK Cells:

IL-15 to Facilitate NK Cell Survival and Expansion

IL-15: 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

Overall Number of Baseline Participants 17
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants
<=18 years
1
   5.9%
Between 18 and 65 years
10
  58.8%
>=65 years
6
  35.3%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 17 participants
57  (14)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants
Female
5
  29.4%
Male
12
  70.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
15
  88.2%
Unknown or Not Reported
2
  11.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
14
  82.4%
More than one race
0
   0.0%
Unknown or Not Reported
3
  17.6%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 17 participants
17
 100.0%
1.Primary Outcome
Title < 5% Marrow Blast, no Circulating Peripheral Blasts and Neutrophil Count of > 1 x 10^9/L
Hide Description Without platelet recovery
Time Frame Day 42 post NK cell infusion
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Preparative Regimen and SubQ rHuIL-15
Hide Arm/Group Description:

Preparative Regimen of Fludarabine and Cyclophosphamide

IL-15 Activation of Donor NK Cells:

IL-15 to Facilitate NK Cell Survival and Expansion

IL-15: 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

Overall Number of Participants Analyzed 15
Measure Type: Count of Participants
Unit of Measure: Participants
5
  33.3%
2.Secondary Outcome
Title In Vivo Expansion (>100) of NK Cells (Defined at CD56+/CD3- Lymphocytes)
Hide Description [Not Specified]
Time Frame Day 14 post NK cell infusion
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Preparative Regimen and SubQ rHuIL-15
Hide Arm/Group Description:

Preparative Regimen of Fludarabine and Cyclophosphamide

IL-15 Activation of Donor NK Cells:

IL-15 to Facilitate NK Cell Survival and Expansion

IL-15: 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

Overall Number of Participants Analyzed 15
Measure Type: Count of Participants
Unit of Measure: Participants
4
  26.7%
3.Secondary Outcome
Title Proportion of Patients Experiencing Grade, 3, 4, and 5 Toxicities (Assessed by CTCAE v. 4)
Hide Description [Not Specified]
Time Frame Days 1-5 and Days 8-12, 24 hours after the last IL-15 dose, Day +28, Day +42
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Preparative Regimen and SubQ rHuIL-15
Hide Arm/Group Description:

Preparative Regimen of Fludarabine and Cyclophosphamide

IL-15 Activation of Donor NK Cells:

IL-15 to Facilitate NK Cell Survival and Expansion

IL-15: 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

Overall Number of Participants Analyzed 17
Measure Type: Count of Participants
Unit of Measure: Participants
10
  58.8%
4.Secondary Outcome
Title Treatment Related Mortality
Hide Description [Not Specified]
Time Frame 6 months post-therapy
Hide Outcome Measure Data
Hide Analysis Population Description
1 patient left the study
Arm/Group Title Preparative Regimen and SubQ rHuIL-15
Hide Arm/Group Description:

Preparative Regimen of Fludarabine and Cyclophosphamide

IL-15 Activation of Donor NK Cells:

IL-15 to Facilitate NK Cell Survival and Expansion

IL-15: 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

Overall Number of Participants Analyzed 16
Measure Type: Count of Participants
Unit of Measure: Participants
2
  12.5%
5.Secondary Outcome
Title Number of Subjects Achieving Complete Response, Defined as in Vivo Donor Derived NK Cell Expansion of > 100 Donor Derived NK Cells.
Hide Description [Not Specified]
Time Frame Day 42 post NK cell infusion
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Preparative Regimen and SubQ rHuIL-15
Hide Arm/Group Description:

Preparative Regimen of Fludarabine and Cyclophosphamide

IL-15 Activation of Donor NK Cells:

IL-15 to Facilitate NK Cell Survival and Expansion

IL-15: 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

Overall Number of Participants Analyzed 15
Measure Type: Count of Participants
Unit of Measure: Participants
1
   6.7%
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Preparative Regimen and SubQ rHuIL-15
Hide Arm/Group Description

Preparative Regimen of Fludarabine and Cyclophosphamide

IL-15 Activation of Donor NK Cells:

IL-15 to Facilitate NK Cell Survival and Expansion

IL-15: 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

All-Cause Mortality
Preparative Regimen and SubQ rHuIL-15
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Preparative Regimen and SubQ rHuIL-15
Affected / at Risk (%)
Total   12/17 (70.59%) 
Blood and lymphatic system disorders   
Febrile neutropenia   1/17 (5.88%) 
Immune system disorders   
Cytokine Release Syndrome - Grade 3   3/17 (17.65%) 
Cytokine Release Syndrome - Grade 4   2/17 (11.76%) 
Infections and infestations   
Abdominal Infection   1/17 (5.88%) 
Endocarditis Infective   1/17 (5.88%) 
Hepatitis Viral   1/17 (5.88%) 
Infections and Infestations - Other, specify   1/17 (5.88%) 
Lung Infection   1/17 (5.88%) 
Sepsis   1/17 (5.88%) 
Sinusitis   1/17 (5.88%) 
Musculoskeletal and connective tissue disorders   
Muscle Weakness Lower Limb   1/17 (5.88%) 
Nervous system disorders   
Intracranial Hemorrhage   1/17 (5.88%) 
Seizure   1/17 (5.88%) 
Renal and urinary disorders   
Acute Kidney Injury   1/17 (5.88%) 
Respiratory, thoracic and mediastinal disorders   
Adult Respiratory Distress Syndrome   1/17 (5.88%) 
Vascular disorders   
Hypotension   1/17 (5.88%) 
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Preparative Regimen and SubQ rHuIL-15
Affected / at Risk (%)
Total   15/17 (88.24%) 
Blood and lymphatic system disorders   
Febrile neutropenia   2/17 (11.76%) 
General disorders   
Fatigue   2/17 (11.76%) 
Flu like symptoms   1/17 (5.88%) 
Gait disturbance   1/17 (5.88%) 
Mouth/tongue sores   1/17 (5.88%) 
Immune system disorders   
Cytokine release syndrome   5/17 (29.41%) 
Infections and infestations   
Infections and infestations - Other, specify   1/17 (5.88%) 
Sepsis   1/17 (5.88%) 
Sinusitis   1/17 (5.88%) 
Investigations   
Alanine aminotransferase increased   1/17 (5.88%) 
Aspartate aminotransferase increased   1/17 (5.88%) 
Blood bilirubin increased   1/17 (5.88%) 
Creatinine increased   1/17 (5.88%) 
Weight gain   5/17 (29.41%) 
Metabolism and nutrition disorders   
Hypernatremia   1/17 (5.88%) 
Musculoskeletal and connective tissue disorders   
Back pain   1/17 (5.88%) 
Chest wall pain   1/17 (5.88%) 
Pain in extremity   1/17 (5.88%) 
Nervous system disorders   
Encephalopathy   2/17 (11.76%) 
Headache   4/17 (23.53%) 
Intracranial hemorrhage   1/17 (5.88%) 
Nervous system disorders - Other, specify   1/17 (5.88%) 
Seizure   1/17 (5.88%) 
Non Convulsive Status Epilipticus   1/17 (5.88%) 
Psychiatric disorders   
Confusion   4/17 (23.53%) 
Renal and urinary disorders   
Acute kidney injury   2/17 (11.76%) 
Respiratory, thoracic and mediastinal disorders   
Hiccups   1/17 (5.88%) 
Hypoxia   1/17 (5.88%) 
Pneumonitis   1/17 (5.88%) 
Pulmonary edema   3/17 (17.65%) 
Respiratory failure   1/17 (5.88%) 
Skin and subcutaneous tissue disorders   
Periorbital edema   2/17 (11.76%) 
Pruritus   1/17 (5.88%) 
Rash maculo-papular   1/17 (5.88%) 
Vascular disorders   
Hypotension   2/17 (11.76%) 
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Yumna Akhtar - Ct.gov Manager
Organization: University of Minnesota Masonic Cancer Center
Phone: 612-624-6313
Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT02395822     History of Changes
Other Study ID Numbers: 2014LS092
First Submitted: February 16, 2015
First Posted: March 24, 2015
Results First Submitted: December 12, 2017
Results First Posted: January 10, 2018
Last Update Posted: February 20, 2018