Trial Outcomes & Findings for Safety Trial of NK Cell DLI 3-5/6 Family Member Following Nonmyeloablative ASCT (NCT NCT00586703)
NCT ID: NCT00586703
Last Updated: 2014-06-12
Results Overview
Evaluate the safety of NK cell infusion using CD56 monoclonal antibody following nonmyeloablative stem cell transplantation from mismatched donors: Toxicity including mortality, occurrence of acute graft versus host disease (aGVHD) and other severe toxicity.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
21 participants
Primary outcome timeframe
8 weeks
Results posted on
2014-06-12
Participant Flow
21 Patients were recruited through the Adult Bone Marrow Transplant Program at Duke University Medical Center. Recruitment began in April, 2005 and ended in March, 2011. Patients who met the eligibility criteria were approached about the study and informed consent was conducted for those who agreed.
Prior to donor lymphocyte infusion (DLI), disease state was documented: Complete history Physical exam Performance status Routine lab tests Radiographic tests Subjects didn't continue with treatment with disease progression. 2 subjects withdrew consent; 1 had graft versus host disease; 1 died; 1 subject's donor didn't yield enough cells.
Participant milestones
| Measure |
Experimental: NK-CD56
NK Cell infusion using CD56 monoclonal antibody following nonmyeloablative SCT from mismatched donors
NK Cell Infusion following SCT from mismatched donors : The cells from leukapheresis will be NK selected using a CD56 antibody and a cell column system provided by Miltenyi Biotec. The target cell dose for each NK cell infusion will be up to 1 X 10(7) CD56+ cells/kg patient weight with less than 0.5 X 10(6) CD3+ cells/kg patient weight. The first NK cell infusion will be administered 6 weeks post transplant in patients who have ≤ grade II aGVHD at the time of infusion. Patients will be evaluated for toxicity and response until 20 weeks after the last NK Infusion.
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|---|---|
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Overall Study
STARTED
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16
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Overall Study
COMPLETED
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4
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Overall Study
NOT COMPLETED
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12
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Reasons for withdrawal
| Measure |
Experimental: NK-CD56
NK Cell infusion using CD56 monoclonal antibody following nonmyeloablative SCT from mismatched donors
NK Cell Infusion following SCT from mismatched donors : The cells from leukapheresis will be NK selected using a CD56 antibody and a cell column system provided by Miltenyi Biotec. The target cell dose for each NK cell infusion will be up to 1 X 10(7) CD56+ cells/kg patient weight with less than 0.5 X 10(6) CD3+ cells/kg patient weight. The first NK cell infusion will be administered 6 weeks post transplant in patients who have ≤ grade II aGVHD at the time of infusion. Patients will be evaluated for toxicity and response until 20 weeks after the last NK Infusion.
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|---|---|
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Overall Study
Death
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12
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Baseline Characteristics
Safety Trial of NK Cell DLI 3-5/6 Family Member Following Nonmyeloablative ASCT
Baseline characteristics by cohort
| Measure |
Experimental: NK-CD56
n=21 Participants
Natural Killer (NK) Cell infusion using CD56 monoclonal antibody following nonmyeloablative stem cell transplant (SCT) from mismatched donors
NK Cell Infusion following SCT from mismatched donors: The cells from leukapheresis will be NK selected using a CD56 antibody and a cell column system provided by Miltenyi Biotec. The target cell dose for each NK cell infusion will be up to 1 X 10(7) CD56+ cells/kg patient weight with less than 0.5 X 10(6) CD3+ cells/kg patient weight. The first NK cell infusion will be administered 6 weeks post transplant in patients who have ≤ grade II acute graft-versus host disease (aGVHD) at the time of infusion. Patients will be evaluated for toxicity and response until 20 weeks after the last NK Infusion.
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|---|---|
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Age, Categorical
<=18 years
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0 Participants
n=5 Participants
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Age, Categorical
Between 18 and 65 years
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18 Participants
n=5 Participants
|
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Age, Categorical
>=65 years
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3 Participants
n=5 Participants
|
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Sex: Female, Male
Female
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8 Participants
n=5 Participants
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Sex: Female, Male
Male
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13 Participants
n=5 Participants
|
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Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=5 Participants
|
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Race (NIH/OMB)
Asian
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0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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0 Participants
n=5 Participants
|
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Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
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Race (NIH/OMB)
White
|
17 Participants
n=5 Participants
|
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Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
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Race (NIH/OMB)
Unknown or Not Reported
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1 Participants
n=5 Participants
|
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Ethnicity (NIH/OMB)
Hispanic or Latino
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0 Participants
n=5 Participants
|
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Ethnicity (NIH/OMB)
Not Hispanic or Latino
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21 Participants
n=5 Participants
|
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Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
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Region of Enrollment
United States
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21 participants
n=5 Participants
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PRIMARY outcome
Timeframe: 8 weeksPopulation: Participants who were able to receive infusion.
Evaluate the safety of NK cell infusion using CD56 monoclonal antibody following nonmyeloablative stem cell transplantation from mismatched donors: Toxicity including mortality, occurrence of acute graft versus host disease (aGVHD) and other severe toxicity.
Outcome measures
| Measure |
Experimental: NK-CD56
n=16 Participants
Natural Killer (NK) Cell infusion using CD56 monoclonal antibody following nonmyeloablative stem cell transplant (SCT) from mismatched donors
NK Cell Infusion following SCT from mismatched donors: The cells from leukapheresis will be NK selected using a CD56 antibody and a cell column system provided by Miltenyi Biotec. The target cell dose for each NK cell infusion will be up to 1 X 10(7) CD56+ cells/kg patient weight with less than 0.5 X 10(6) CD3+ cells/kg patient weight. The first NK cell infusion will be administered 6 weeks post transplant in patients who have ≤ grade II acute graft-versus host disease (aGVHD) at the time of infusion. Patients will be evaluated for toxicity and response until 20 weeks after the last NK Infusion.
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Toxicity
Acute Graft versus Host Disease (aGvHD)
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8 participants
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Toxicity
Post-transplant lymphoproliferative disorder
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2 participants
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SECONDARY outcome
Timeframe: 7 yearsPopulation: Participants who completed infusion.
Evaluate the efficacy of the regimen in terms of overall survival (OS).
Outcome measures
| Measure |
Experimental: NK-CD56
n=16 Participants
Natural Killer (NK) Cell infusion using CD56 monoclonal antibody following nonmyeloablative stem cell transplant (SCT) from mismatched donors
NK Cell Infusion following SCT from mismatched donors: The cells from leukapheresis will be NK selected using a CD56 antibody and a cell column system provided by Miltenyi Biotec. The target cell dose for each NK cell infusion will be up to 1 X 10(7) CD56+ cells/kg patient weight with less than 0.5 X 10(6) CD3+ cells/kg patient weight. The first NK cell infusion will be administered 6 weeks post transplant in patients who have ≤ grade II acute graft-versus host disease (aGVHD) at the time of infusion. Patients will be evaluated for toxicity and response until 20 weeks after the last NK Infusion.
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|---|---|
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Efficacy - Overall Survival
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27 months
Interval 4.0 to 84.0
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Adverse Events
Experimental: NK-CD56
Serious events: 0 serious events
Other events: 16 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Experimental: NK-CD56
n=16 participants at risk
Natural Killer (NK) Cell infusion using CD56 monoclonal antibody following nonmyeloablative stem cell transplant (SCT) from mismatched donors
NK Cell Infusion following SCT from mismatched donors: The cells from leukapheresis will be NK selected using a CD56 antibody and a cell column system provided by Miltenyi Biotec. The target cell dose for each NK cell infusion will be up to 1 X 10(7) CD56+ cells/kg patient weight with less than 0.5 X 10(6) CD3+ cells/kg patient weight. The first NK cell infusion will be administered 6 weeks post transplant in patients who have ≤ grade II acute graft-versus host disease (aGVHD) at the time of infusion. Patients will be evaluated for toxicity and response until 20 weeks after the last NK Infusion.
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Investigations
Failure to Engraft
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6.2%
1/16 • Number of events 1 • Patients shall be monitored for toxicity and Graft versus Host Disease every other week until 8 weeks after the last Natural Killer cell Infusion and after that, every 4 weeks for 12 more weeks.
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Cardiac disorders
Atrial Fibrillation
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6.2%
1/16 • Number of events 1 • Patients shall be monitored for toxicity and Graft versus Host Disease every other week until 8 weeks after the last Natural Killer cell Infusion and after that, every 4 weeks for 12 more weeks.
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Cardiac disorders
Atrial Flutter
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6.2%
1/16 • Number of events 1 • Patients shall be monitored for toxicity and Graft versus Host Disease every other week until 8 weeks after the last Natural Killer cell Infusion and after that, every 4 weeks for 12 more weeks.
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Skin and subcutaneous tissue disorders
Dermatology - Skin (other)
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6.2%
1/16 • Number of events 1 • Patients shall be monitored for toxicity and Graft versus Host Disease every other week until 8 weeks after the last Natural Killer cell Infusion and after that, every 4 weeks for 12 more weeks.
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Skin and subcutaneous tissue disorders
Rash
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6.2%
1/16 • Number of events 1 • Patients shall be monitored for toxicity and Graft versus Host Disease every other week until 8 weeks after the last Natural Killer cell Infusion and after that, every 4 weeks for 12 more weeks.
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Gastrointestinal disorders
Diarrhea
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12.5%
2/16 • Number of events 2 • Patients shall be monitored for toxicity and Graft versus Host Disease every other week until 8 weeks after the last Natural Killer cell Infusion and after that, every 4 weeks for 12 more weeks.
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Gastrointestinal disorders
Esophagitis
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6.2%
1/16 • Number of events 1 • Patients shall be monitored for toxicity and Graft versus Host Disease every other week until 8 weeks after the last Natural Killer cell Infusion and after that, every 4 weeks for 12 more weeks.
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Blood and lymphatic system disorders
Hemorrhagic Cystitis
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6.2%
1/16 • Number of events 1 • Patients shall be monitored for toxicity and Graft versus Host Disease every other week until 8 weeks after the last Natural Killer cell Infusion and after that, every 4 weeks for 12 more weeks.
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Blood and lymphatic system disorders
Hemorrhage - GU
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6.2%
1/16 • Number of events 1 • Patients shall be monitored for toxicity and Graft versus Host Disease every other week until 8 weeks after the last Natural Killer cell Infusion and after that, every 4 weeks for 12 more weeks.
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Infections and infestations
Febrile Neutropenia
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12.5%
2/16 • Number of events 2 • Patients shall be monitored for toxicity and Graft versus Host Disease every other week until 8 weeks after the last Natural Killer cell Infusion and after that, every 4 weeks for 12 more weeks.
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Infections and infestations
Infection - other
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6.2%
1/16 • Number of events 1 • Patients shall be monitored for toxicity and Graft versus Host Disease every other week until 8 weeks after the last Natural Killer cell Infusion and after that, every 4 weeks for 12 more weeks.
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Infections and infestations
Infection-bacterial with grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L)
|
31.2%
5/16 • Number of events 6 • Patients shall be monitored for toxicity and Graft versus Host Disease every other week until 8 weeks after the last Natural Killer cell Infusion and after that, every 4 weeks for 12 more weeks.
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Infections and infestations
Infection-bacterial with normal ANC or grade 1 or 2 neutrophils
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18.8%
3/16 • Number of events 5 • Patients shall be monitored for toxicity and Graft versus Host Disease every other week until 8 weeks after the last Natural Killer cell Infusion and after that, every 4 weeks for 12 more weeks.
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Infections and infestations
Infection-viral without febrile neutropenia
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18.8%
3/16 • Number of events 3 • Patients shall be monitored for toxicity and Graft versus Host Disease every other week until 8 weeks after the last Natural Killer cell Infusion and after that, every 4 weeks for 12 more weeks.
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Metabolism and nutrition disorders
Hyperbilirubinemia
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6.2%
1/16 • Number of events 1 • Patients shall be monitored for toxicity and Graft versus Host Disease every other week until 8 weeks after the last Natural Killer cell Infusion and after that, every 4 weeks for 12 more weeks.
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Metabolism and nutrition disorders
AST; SGOT
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6.2%
1/16 • Number of events 1 • Patients shall be monitored for toxicity and Graft versus Host Disease every other week until 8 weeks after the last Natural Killer cell Infusion and after that, every 4 weeks for 12 more weeks.
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Metabolism and nutrition disorders
Creatinine
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6.2%
1/16 • Number of events 1 • Patients shall be monitored for toxicity and Graft versus Host Disease every other week until 8 weeks after the last Natural Killer cell Infusion and after that, every 4 weeks for 12 more weeks.
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Musculoskeletal and connective tissue disorders
Arthritis
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6.2%
1/16 • Number of events 1 • Patients shall be monitored for toxicity and Graft versus Host Disease every other week until 8 weeks after the last Natural Killer cell Infusion and after that, every 4 weeks for 12 more weeks.
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Nervous system disorders
Neuropathy
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6.2%
1/16 • Number of events 1 • Patients shall be monitored for toxicity and Graft versus Host Disease every other week until 8 weeks after the last Natural Killer cell Infusion and after that, every 4 weeks for 12 more weeks.
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Respiratory, thoracic and mediastinal disorders
Hypoxia
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12.5%
2/16 • Number of events 2 • Patients shall be monitored for toxicity and Graft versus Host Disease every other week until 8 weeks after the last Natural Killer cell Infusion and after that, every 4 weeks for 12 more weeks.
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Respiratory, thoracic and mediastinal disorders
Pneumonitis
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6.2%
1/16 • Number of events 1 • Patients shall be monitored for toxicity and Graft versus Host Disease every other week until 8 weeks after the last Natural Killer cell Infusion and after that, every 4 weeks for 12 more weeks.
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Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Secondary Malignancy
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6.2%
1/16 • Number of events 1 • Patients shall be monitored for toxicity and Graft versus Host Disease every other week until 8 weeks after the last Natural Killer cell Infusion and after that, every 4 weeks for 12 more weeks.
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Reproductive system and breast disorders
Erectile Dysfunction
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6.2%
1/16 • Number of events 1 • Patients shall be monitored for toxicity and Graft versus Host Disease every other week until 8 weeks after the last Natural Killer cell Infusion and after that, every 4 weeks for 12 more weeks.
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Blood and lymphatic system disorders
Blood/Bone Marrow - Blast Crisis
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6.2%
1/16 • Number of events 1 • Patients shall be monitored for toxicity and Graft versus Host Disease every other week until 8 weeks after the last Natural Killer cell Infusion and after that, every 4 weeks for 12 more weeks.
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Infections and infestations
Infection-viral with normal ANC or grade 1 or 2 neutrophils
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31.2%
5/16 • Number of events 7 • Patients shall be monitored for toxicity and Graft versus Host Disease every other week until 8 weeks after the last Natural Killer cell Infusion and after that, every 4 weeks for 12 more weeks.
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Infections and infestations
Infection-viral with Grade 3 or 4 neutrophils (ANC <1.0 x 10e
|
43.8%
7/16 • Number of events 11 • Patients shall be monitored for toxicity and Graft versus Host Disease every other week until 8 weeks after the last Natural Killer cell Infusion and after that, every 4 weeks for 12 more weeks.
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Blood and lymphatic system disorders
Hypervolemia
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6.2%
1/16 • Number of events 1 • Patients shall be monitored for toxicity and Graft versus Host Disease every other week until 8 weeks after the last Natural Killer cell Infusion and after that, every 4 weeks for 12 more weeks.
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Infections and infestations
Infection-bacterial without febrile neutropenia
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6.2%
1/16 • Number of events 1 • Patients shall be monitored for toxicity and Graft versus Host Disease every other week until 8 weeks after the last Natural Killer cell Infusion and after that, every 4 weeks for 12 more weeks.
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place