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

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ClinicalTrials.gov Identifier: NCT00586690
Recruitment Status : Completed
First Posted : January 4, 2008
Results First Posted : June 2, 2014
Last Update Posted : February 8, 2017
Sponsor:
Information provided by (Responsible Party):
David Rizzieri, MD, Duke University

Tracking Information
First Submitted Date  ICMJE December 21, 2007
First Posted Date  ICMJE January 4, 2008
Results First Submitted Date  ICMJE February 5, 2014
Results First Posted Date  ICMJE June 2, 2014
Last Update Posted Date February 8, 2017
Study Start Date  ICMJE May 2005
Actual Primary Completion Date May 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 2, 2014)
Toxicity [ Time Frame: 5 months ]
Evaluate the toxicity post-infusion including mortality, occurrence of acute graft versus host disease (GVHD) and other severe toxicity until a minimum of 8 weeks following the last infusion, then at least monthly for 3 additional months. Unacceptable toxicity was defined as grade ≥ III aGVHD of the gut or liver or Grade 4 aGVHD of the skin lasting > 7 days; other Grade 4 toxicity from the procedure in the major organs that lasted > 5 days; or treatment-related mortality (TRM). Though these infusions are provided early following transplantation and severe toxicity could still have occurred due to the primary transplant procedure, for this study any aGVHD or other toxicities occurring after the first day of infusion of the natural killer (NK) cell enriched Donor Lymphocyte Infusions (DLIs) is considered here as study related.
Original Primary Outcome Measures  ICMJE
 (submitted: December 21, 2007)
Evaluate the safety of NK cell infusion using CD56 monoclonal antibody following nonmyeloablative stem cell transplantation from matched donors: toxicity including mortality, occurrence of acute GVHD and other severe toxicity [ Time Frame: 2 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 4, 2016)
  • Efficacy - Progression Free Survival [ Time Frame: 3 years ]
    Evaluate efficacy of natural killer (NK) cell infusions in terms of progression free survival (PFS) in number of months without disease progression.
  • Efficacy - Overall Survival [ Time Frame: 8 years ]
    Evaluate efficacy of natural killer (NK) cell infusions in terms of overall survival (OS).
  • Efficacy - Disease Progression [ Time Frame: 3 years ]
    Evaluate efficacy of natural killer (NK) cell infusions in terms of number of patients with disease progression.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 21, 2007)
  • Evaluate efficacy of NK cell infusions in terms of response, progression free, and overall survival [ Time Frame: 2 years ]
  • Evaluate the recovery of immune function post engraftment with this regimen [ Time Frame: 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety Trial of NK DLI From 6/6 HLA Matched Family Member Following Nonmyeloablative ASCT
Official Title  ICMJE Safety Trial of Natural Killer (NK) Cell Donor Lymphocyte Infusions(DLI) From 6/6 Human Leukocyte Antigen (HLA) Matched Family Member Following Nonmyeloablative Allogeneic Stem Cell Transplantation (ASCT)
Brief Summary Evaluate the safety of natural killer (NK) cell infusion using CD56 monoclonal antibody selected with Miltenyi Biotec system following nonmyeloablative stem cell transplantation (SCT) from matched donors. This pilot study will evaluate toxicity including mortality, occurrence of acute graft versus host disease and other severe toxicity.
Detailed Description

The use of non-selected donor lymphocyte infusions (DLIs) (to help early immune recovery and induce antitumor response) following nonmyeloablative allogeneic stem cell transplantation (ASCT) is also complicated by the risk of acute graft versus host disease (aGVHD) with 30-40% of patients experiencing grade III-IV aGVHD. Data suggests that the use of natural killer (NK) cells (instead of nonselected DLIs) in this setting may mediate a graft versus tumor (GVT) effect independently of aGVHD.

This pilot study is designed to evaluate the efficacy and toxicity of donor natural killer (NK) cell selection and infusion following nonmyeloablative allogeneic stem cell transplantation (ASCT) from matched donors.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lymphoma
Intervention  ICMJE
  • Device: 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.
    Other Name: CD56 monoclonal antibody
  • Procedure: 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.
Study Arms  ICMJE
  • Experimental: NK Cell Infusion
    Natural Killer (NK) Cell infusion using CD56 monoclonal antibody
    Intervention: Device: NK Cell infusion using CD56 monoclonal antibody
  • 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.
    Intervention: Procedure: Donor Apheresis
Publications * Rizzieri DA, Storms R, Chen DF, Long G, Yang Y, Nikcevich DA, Gasparetto C, Horwitz M, Chute J, Sullivan K, Hennig T, Misra D, Apple C, Baker M, Morris A, Green PG, Hasselblad V, Chao NJ. Natural killer cell-enriched donor lymphocyte infusions from A 3-6/6 HLA matched family member following nonmyeloablative allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2010 Aug;16(8):1107-14. doi: 10.1016/j.bbmt.2010.02.018. Epub 2010 Feb 24.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 2, 2014)
47
Original Estimated Enrollment  ICMJE
 (submitted: December 21, 2007)
32
Actual Study Completion Date  ICMJE November 2013
Actual Primary Completion Date May 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with who have undergone a non-myeloablative allogeneic transplant, using a 6/6 human leukocyte antigen (HLA) matched sibling donor. Measureable disease is not needed at study entry.
  • Performance status must be Karnofsky 50-100%.
  • Donor cellular engraftment of at least 2.5% from the non-myeloablative procedure.
  • ≤ Grade 2 acute Graft versus Host Disease (aGvHD) at time of infusion of natural killer (NK) cell infusion. Patients with treated aGVHD must be on a stable dose of therapy (no increase in immunosuppressive therapy for the 2 weeks before planned natural killer cell infusion [NKI]). The dosage/level of immunosuppressive therapy at the time of NKI should be no greater than 1 mg/kg of prednisone daily or mycophenolate 1000 mg bid daily or cyclosporine with a target level of 200 or equivalent.
  • Estimated survival at least 8 weeks.
  • Age > or equal to 18 years of age.

Exclusion Criteria:

  • Pregnant or lactating women,
  • Patients with other major medical or psychiatric illnesses, which the treating physician feels, could seriously compromise tolerance to this protocol.
  • Patients who had biopsy proven overall Grade 4 GVHD lasting longer than 7 days, from the non-myeloablative therapy, are not eligible
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00586690
Other Study ID Numbers  ICMJE Pro00005124
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party David Rizzieri, MD, Duke University
Study Sponsor  ICMJE David Rizzieri, MD
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: David Rizzieri, MD Duke Health
PRS Account Duke University
Verification Date January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP