Trial Outcomes & Findings for MT2014-25: Haplo NK With SQ IL-15 in Adult Relapsed or Refractory AML Patients (NCT NCT02395822)
NCT ID: NCT02395822
Last Updated: 2018-02-20
Results Overview
Without platelet recovery
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
17 participants
Primary outcome timeframe
Day 42 post NK cell infusion
Results posted on
2018-02-20
Participant Flow
Participant milestones
| Measure |
Preparative Regimen and SubQ rHuIL-15
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 Study
STARTED
|
17
|
|
Overall Study
COMPLETED
|
15
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Preparative Regimen and SubQ rHuIL-15
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 Study
Withdrawal by Subject
|
1
|
|
Overall Study
Death
|
1
|
Baseline Characteristics
MT2014-25: Haplo NK With SQ IL-15 in Adult Relapsed or Refractory AML Patients
Baseline characteristics by cohort
| Measure |
Preparative Regimen and SubQ rHuIL-15
n=17 Participants
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
|
|---|---|
|
Age, Categorical
<=18 years
|
1 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
10 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
6 Participants
n=5 Participants
|
|
Age, Continuous
|
57 Years
STANDARD_DEVIATION 14 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
15 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
14 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
17 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 42 post NK cell infusionWithout platelet recovery
Outcome measures
| Measure |
Preparative Regimen and SubQ rHuIL-15
n=15 Participants
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
|
|---|---|
|
< 5% Marrow Blast, no Circulating Peripheral Blasts and Neutrophil Count of > 1 x 10^9/L
|
5 Participants
|
SECONDARY outcome
Timeframe: Day 14 post NK cell infusionOutcome measures
| Measure |
Preparative Regimen and SubQ rHuIL-15
n=15 Participants
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
|
|---|---|
|
In Vivo Expansion (>100) of NK Cells (Defined at CD56+/CD3- Lymphocytes)
|
4 Participants
|
SECONDARY outcome
Timeframe: Days 1-5 and Days 8-12, 24 hours after the last IL-15 dose, Day +28, Day +42Outcome measures
| Measure |
Preparative Regimen and SubQ rHuIL-15
n=17 Participants
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
|
|---|---|
|
Proportion of Patients Experiencing Grade, 3, 4, and 5 Toxicities (Assessed by CTCAE v. 4)
|
10 Participants
|
SECONDARY outcome
Timeframe: 6 months post-therapyPopulation: 1 patient left the study
Outcome measures
| Measure |
Preparative Regimen and SubQ rHuIL-15
n=16 Participants
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
|
|---|---|
|
Treatment Related Mortality
|
2 Participants
|
SECONDARY outcome
Timeframe: Day 42 post NK cell infusionOutcome measures
| Measure |
Preparative Regimen and SubQ rHuIL-15
n=15 Participants
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
|
|---|---|
|
Number of Subjects Achieving Complete Response, Defined as in Vivo Donor Derived NK Cell Expansion of > 100 Donor Derived NK Cells.
|
1 Participants
|
Adverse Events
Preparative Regimen and SubQ rHuIL-15
Serious events: 12 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Preparative Regimen and SubQ rHuIL-15
n=17 participants at risk
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
|
|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
5.9%
1/17
|
|
Immune system disorders
Cytokine Release Syndrome - Grade 3
|
17.6%
3/17
|
|
Immune system disorders
Cytokine Release Syndrome - Grade 4
|
11.8%
2/17
|
|
Infections and infestations
Abdominal Infection
|
5.9%
1/17
|
|
Infections and infestations
Endocarditis Infective
|
5.9%
1/17
|
|
Infections and infestations
Hepatitis Viral
|
5.9%
1/17
|
|
Infections and infestations
Infections and Infestations - Other, specify
|
5.9%
1/17
|
|
Infections and infestations
Lung Infection
|
5.9%
1/17
|
|
Infections and infestations
Sepsis
|
5.9%
1/17
|
|
Infections and infestations
Sinusitis
|
5.9%
1/17
|
|
Musculoskeletal and connective tissue disorders
Muscle Weakness Lower Limb
|
5.9%
1/17
|
|
Nervous system disorders
Intracranial Hemorrhage
|
5.9%
1/17
|
|
Nervous system disorders
Seizure
|
5.9%
1/17
|
|
Renal and urinary disorders
Acute Kidney Injury
|
5.9%
1/17
|
|
Respiratory, thoracic and mediastinal disorders
Adult Respiratory Distress Syndrome
|
5.9%
1/17
|
|
Vascular disorders
Hypotension
|
5.9%
1/17
|
Other adverse events
| Measure |
Preparative Regimen and SubQ rHuIL-15
n=17 participants at risk
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
|
|---|---|
|
Renal and urinary disorders
Acute kidney injury
|
11.8%
2/17
|
|
Investigations
Alanine aminotransferase increased
|
5.9%
1/17
|
|
Investigations
Aspartate aminotransferase increased
|
5.9%
1/17
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.9%
1/17
|
|
Investigations
Blood bilirubin increased
|
5.9%
1/17
|
|
Musculoskeletal and connective tissue disorders
Chest wall pain
|
5.9%
1/17
|
|
Psychiatric disorders
Confusion
|
23.5%
4/17
|
|
Investigations
Creatinine increased
|
5.9%
1/17
|
|
Immune system disorders
Cytokine release syndrome
|
29.4%
5/17
|
|
Nervous system disorders
Encephalopathy
|
11.8%
2/17
|
|
General disorders
Fatigue
|
11.8%
2/17
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
11.8%
2/17
|
|
General disorders
Flu like symptoms
|
5.9%
1/17
|
|
General disorders
Gait disturbance
|
5.9%
1/17
|
|
Nervous system disorders
Headache
|
23.5%
4/17
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
5.9%
1/17
|
|
Metabolism and nutrition disorders
Hypernatremia
|
5.9%
1/17
|
|
Vascular disorders
Hypotension
|
11.8%
2/17
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
5.9%
1/17
|
|
Infections and infestations
Infections and infestations - Other, specify
|
5.9%
1/17
|
|
Nervous system disorders
Intracranial hemorrhage
|
5.9%
1/17
|
|
Nervous system disorders
Nervous system disorders - Other, specify
|
5.9%
1/17
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.9%
1/17
|
|
Skin and subcutaneous tissue disorders
Periorbital edema
|
11.8%
2/17
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
5.9%
1/17
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.9%
1/17
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary edema
|
17.6%
3/17
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
5.9%
1/17
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
5.9%
1/17
|
|
Nervous system disorders
Seizure
|
5.9%
1/17
|
|
Infections and infestations
Sepsis
|
5.9%
1/17
|
|
Infections and infestations
Sinusitis
|
5.9%
1/17
|
|
Investigations
Weight gain
|
29.4%
5/17
|
|
General disorders
Mouth/tongue sores
|
5.9%
1/17
|
|
Nervous system disorders
Non Convulsive Status Epilipticus
|
5.9%
1/17
|
Additional Information
Yumna Akhtar - Ct.gov Manager
University of Minnesota Masonic Cancer Center
Phone: 612-624-6313
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place