Safety Trial of NK DLI From 6/6 HLA Matched Family Member Following Nonmyeloablative ASCT

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
David Rizzieri, MD, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT00586690
First received: December 21, 2007
Last updated: May 2, 2014
Last verified: January 2014
Results First Received: February 5, 2014  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Lymphoma
Interventions: Device: NK Cell infusion using CD56 monoclonal antibody
Procedure: Donor Apheresis

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Twenty five participants were recruited through the Adult Bone Marrow Transplant Program at Duke University Medical Center. Recruitment began in May, 2005 and ended in April, 2010. Patients who met the eligibility criteria were approached about the study and informed consent was conducted for those who agreed.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Prior to initiating therapy, donors and subjects will have complete history, physical exam, routine laboratory tests, and/or radiographic tests. Recipients may have Bone marrow aspirate/biopsy repeated to check for prior abnormalities. If disease progression present, patient didn't continue with treatment.

Reporting Groups
  Description
NK Cell Infusion NK Cell infusion using CD56 monoclonal antibody: The cells from leukapheresis will be natural killer (NK) cell 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.
Donor Apheresis Leukapheresis was repeated daily up to 3 days until the target dose of cells was reached (preferably without donor receiving growth factors). When possible, cells were transfused immediately after collection and processing. If collections occurred during initial mobilization at the time of stem cell transplant, the donor was off growth factor for >24 hours. These collections, which are extra cells collected from the donor following initial collections for transplant were sufficient for the natural killer cells used in the trial. The cells were NK selected using a CD56 antibody (CliniMACS CD56 Reagent), CliniMACSplus instrument and CliniMACS tubing set provided by Miltenyi Biotec using the company protocol (Miltenyi Biotec Inc, Auburn, California). Pre and post processing cell count, viability, Hematopoietic Progenitor Cell Assay (HPCA) and flow analysis were done.

Participant Flow:   Overall Study
    NK Cell Infusion     Donor Apheresis  
STARTED     21 [1]   22  
COMPLETED     5     22  
NOT COMPLETED     16     0  
Death                 2                 0  
Disease Progression                 10                 0  
Adverse Event                 1                 0  
Lack of Efficacy                 2                 0  
Lab can't accommodate                 1                 0  
[1] Four consented subjects were screen failures.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Eligible adult patients were those who engrafted following a fludarabine based T cell depleted non-myeloablative allogeneic transplant regimen with alemtuzumab. Donors were the same HLA 6/6 matched family member used for the allogeneic transplantation.

Reporting Groups
  Description
NK Cell Infusion Natural Killer (NK) Cell infusion using CD56 monoclonal antibody: The cells from leukapheresis will be natural killer (NK) cell 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.
Donor Apheresis Apheresis repeated daily up to 3 days until target dose of cells reached (preferably without donor receiving growth factors). Cells were transfused immediately after collection and processing. If collections occurred during initial mobilization at the time of stem cell transplant, the donor was off growth factor for >24 hours. These extra cell collections from the donor were sufficient for the natural killer cells used in the trial. The cells were NK selected using a CD56 antibody (CliniMACS CD56 Reagent), CliniMACSplus instrument and CliniMACS tubing set provided by Miltenyi Biotec using the company protocol (Miltenyi Biotec Inc, Auburn, California). Pre and post processing cell count, viability, Hematopoietic Progenitor Cell Assay (HPCA) and flow analysis were done.
Total Total of all reporting groups

Baseline Measures
    NK Cell Infusion     Donor Apheresis     Total  
Number of Participants  
[units: participants]
  25     22     47  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     21     18     39  
>=65 years     4     4     8  
Gender  
[units: participants]
     
Female     9     8     17  
Male     16     14     30  
Race (NIH/OMB)  
[units: 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     1     1     2  
White     24     21     45  
More than one race     0     0     0  
Unknown or Not Reported     0     0     0  
Ethnicity (NIH/OMB)  
[units: participants]
     
Hispanic or Latino     0     0     0  
Not Hispanic or Latino     25     22     47  
Unknown or Not Reported     0     0     0  
Region of Enrollment  
[units: participants]
     
United States     25     22     47  



  Outcome Measures
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1.  Primary:   Toxicity   [ Time Frame: 5 months ]

2.  Secondary:   Efficacy - Progression Free Survival   [ Time Frame: 3 years ]

3.  Secondary:   Efficacy - Overall Survival   [ Time Frame: 8 years ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Results Point of Contact:  
Name/Title: David Rizzieri, MD
Organization: Duke University Medical Center
phone: 919-668-1040
e-mail: david.rizzieri@duke.edu


Publications of Results:

Responsible Party: David Rizzieri, MD, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT00586690     History of Changes
Other Study ID Numbers: Pro00005124
Study First Received: December 21, 2007
Results First Received: February 5, 2014
Last Updated: May 2, 2014
Health Authority: United States: Food and Drug Administration