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Safety Trial of NK Cell DLI 3-5/6 Family Member Following Nonmyeloablative ASCT

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ClinicalTrials.gov Identifier: NCT00586703
Recruitment Status : Completed
First Posted : January 4, 2008
Results First Posted : March 27, 2014
Last Update Posted : June 12, 2014
Sponsor:
Information provided by (Responsible Party):
David Rizzieri, MD, Duke University

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Lymphoma
Intervention Device: NK-CD56
Enrollment 21
Recruitment Details 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.
Pre-assignment Details

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.

Arm/Group Title Experimental: NK-CD56
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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.

Period Title: Overall Study
Started 16
Completed 4
Not Completed 12
Reason Not Completed
Death             12
Arm/Group Title Experimental: NK-CD56
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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.

Overall Number of Baseline Participants 21
Hide Baseline Analysis Population Description
Participants who were eligible for study.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants
<=18 years
0
   0.0%
Between 18 and 65 years
18
  85.7%
>=65 years
3
  14.3%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants
Female
8
  38.1%
Male
13
  61.9%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 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
3
  14.3%
White
17
  81.0%
More than one race
0
   0.0%
Unknown or Not Reported
1
   4.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
21
 100.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 21 participants
21
1.Primary Outcome
Title Toxicity
Hide Description 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.
Time Frame 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who were able to receive infusion.
Arm/Group Title Experimental: NK-CD56
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 16
Measure Type: Number
Unit of Measure: participants
Acute Graft versus Host Disease (aGvHD) 8
Post-transplant lymphoproliferative disorder 2
2.Secondary Outcome
Title Efficacy - Overall Survival
Hide Description Evaluate the efficacy of the regimen in terms of overall survival (OS).
Time Frame 7 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who completed infusion.
Arm/Group Title Experimental: NK-CD56
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 16
Mean (Full Range)
Unit of Measure: months
27
(4 to 84)
Time Frame 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.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Experimental: NK-CD56
Hide Arm/Group Description

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.

All-Cause Mortality
Experimental: NK-CD56
Affected / at Risk (%)
Total   --/--    
Hide Serious Adverse Events
Experimental: NK-CD56
Affected / at Risk (%) # Events
Total   0/16 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Experimental: NK-CD56
Affected / at Risk (%) # Events
Total   16/16 (100.00%)    
Blood and lymphatic system disorders   
Hemorrhagic Cystitis * 1  1/16 (6.25%)  1
Hemorrhage - GU * 1  1/16 (6.25%)  1
Blood/Bone Marrow - Blast Crisis * 1 [1]  1/16 (6.25%)  1
Hypervolemia * 1  1/16 (6.25%)  1
Cardiac disorders   
Atrial Fibrillation * 1 [2]  1/16 (6.25%)  1
Atrial Flutter * 1 [2]  1/16 (6.25%)  1
Gastrointestinal disorders   
Diarrhea * 1  2/16 (12.50%)  2
Esophagitis * 1 [3]  1/16 (6.25%)  1
Infections and infestations   
Febrile Neutropenia * 1 [4]  2/16 (12.50%)  2
Infection - other * 1 [5]  1/16 (6.25%)  1
Infection-bacterial with grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L) * 1 [6]  5/16 (31.25%)  6
Infection-bacterial with normal ANC or grade 1 or 2 neutrophils * 1 [7]  3/16 (18.75%)  5
Infection-viral without febrile neutropenia * 1 [8]  3/16 (18.75%)  3
Infection-viral with normal ANC or grade 1 or 2 neutrophils * 1 [9]  5/16 (31.25%)  7
Infection-viral with Grade 3 or 4 neutrophils (ANC <1.0 x 10e * 1 [10]  7/16 (43.75%)  11
Infection-bacterial without febrile neutropenia * 1 [11]  1/16 (6.25%)  1
Investigations   
Failure to Engraft * 1  1/16 (6.25%)  1
Metabolism and nutrition disorders   
Hyperbilirubinemia * 1  1/16 (6.25%)  1
AST; SGOT * 1 [12]  1/16 (6.25%)  1
Creatinine * 1 [13]  1/16 (6.25%)  1
Musculoskeletal and connective tissue disorders   
Arthritis * 1  1/16 (6.25%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Secondary Malignancy * 1 [14]  1/16 (6.25%)  1
Nervous system disorders   
Neuropathy * 1 [15]  1/16 (6.25%)  1
Reproductive system and breast disorders   
Erectile Dysfunction * 1  1/16 (6.25%)  1
Respiratory, thoracic and mediastinal disorders   
Hypoxia * 1  2/16 (12.50%)  2
Pneumonitis * 1  1/16 (6.25%)  1
Skin and subcutaneous tissue disorders   
Dermatology - Skin (other) * 1 [16]  1/16 (6.25%)  1
Rash * 1 [17]  1/16 (6.25%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (3.0)
[1]
Relapsed Acute myeloid leukemia
[2]
Supraventricular and nodal arrhythmia
[3]
ulcerative esophagitis
[4]
fever of unknown origin without clinically or microbiologically documented infection)(ANC <1.0 x 10e9/L, fever >=38.5 degrees C
[5]
Cytomegalovirus Retinitis
[6]
C-diff; Gram-rod bacteria; Methicillin-resistant Staphylococcus aureus (MRSA); Klebsiella; E-coli; Bacillus and Coag Negative Staph
[7]
Osteomyelitis; Pseudomonas bacteremia; Staph; Enterococcus
[8]
Cytomegalovirus; Viremia; Parainfluenza
[9]
Cytomegalovirus; Viremia; Polyoma; Herpes; Varicella Zoster
[10]
Adenovirus; Cytomegalovirus; Parainfluenza; Polyoma; Human Herpes Virus 6; Viremia
[11]
Gram positive Cocci bacteria
[12]
Aspartate transaminase; serum glutamic oxaloacetic transaminase
[13]
4.3 mg/dl
[14]
Post-transplant lymphoproliferative disorder
[15]
Motor neuropathy
[16]
Squamous cell carcinoma - left chest
[17]
desquamation - contact dermatitis on neck and face
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: David Rizzieri, MD
Organization: Duke University Medical Center
Phone: 919-668-1040
EMail: david.rizzieri@duke.edu
Layout table for additonal information
Responsible Party: David Rizzieri, MD, Duke University
ClinicalTrials.gov Identifier: NCT00586703    
Other Study ID Numbers: Pro00005123
First Submitted: December 21, 2007
First Posted: January 4, 2008
Results First Submitted: February 5, 2014
Results First Posted: March 27, 2014
Last Update Posted: June 12, 2014