Safety Trial of NK DLI From 6/6 HLA Matched Family Member Following Nonmyeloablative ASCT - Full Text View

Sponsored by:	Duke University
Information provided by:	Duke University
ClinicalTrials.gov Identifier:	NCT00586690

Purpose

Evaluate the safety of NK cell infusion using CD56 monoclonal antibody selected with Miltenyi Biotec system following nonmyeloablative stem cell transplantation from matched donors. This pilot study will evaluate toxicity including mortality, occurrence of acute graft versus host disease and other severe toxicity.

Condition	Intervention	Phase
Lymphoma	Procedure: NK Cell Infusion following SCT from matched donors	Phase I

MedlinePlus related topics: Lymphoma

Drug Information available for: Immunoglobulins Globulin, Immune

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Safety Study
Official Title:	Safety Trial of NK Cell Donor Lymphocyte Infusions From 6/6 HLA Matched Family Member Following Nonmyeloablative Allogeneic Stem Cell Transplantation

Further study details as provided by Duke University:

Primary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Evaluate efficacy of NK cell infusions in terms of response, progression free, and overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Evaluate the recovery of immune function post engraftment with this regimen [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	32
Study Start Date:	May 2005
Estimated Study Completion Date:	May 2010
Estimated Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
I: Experimental NK Cell infusion using CD56 monoclonal antibody following nonmyeloablative SCT from matched donors	Procedure: NK Cell Infusion following SCT from matched 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.

Arms

Assigned Interventions

I: Experimental

NK Cell infusion using CD56 monoclonal antibody following nonmyeloablative SCT from matched donors

Procedure: NK Cell Infusion following SCT from matched 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.

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 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 feasibility and toxicity of donor natural killer (NK) cell selection and infusion following nonmyeloablative allogeneic stem cell transplantation from matched donors. Additionally, we will assess immune reconstitution/function post NK cell infusion and evaluate efficacy.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with who have undergone a non-myeloablative allogeneic transplant, using a 6/6 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 GVHD at time of infusion of NK cell infusion. Patients with treated acute GVHD must be on a stable dose of therapy (no increase in immunosuppressive therapy for the 2 weeks before planned NKI). The dosage/level of immunosuppressive therapy at the time of NKI should be no greater than 1 mg/kg of prednisone daily or mycophenylate 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00586690

Contacts

Contact: Jennifer Loftis, RN, BSN, OCN	919-668-1939	lofti002@mc.duke.edu
Contact: Donna Adams	919-668-4716	adams068@mc.duke.edu

Locations

United States, North Carolina
Duke University Health System	Recruiting
Durham, North Carolina, United States, 27710
Contact: David Rizzieri, MD 919-668-1014 rizzi003@mc.duke.edu
Contact: Nelson Chao, MD 919-668-1011 chao0002@mc.duke.edu

Sponsors and Collaborators

Duke University

Investigators

Principal Investigator:

David Rizzieri, MD

Duke University Health System

More Information

Responsible Party:	Duke University Health System, Department of Medicine, Cell Therapy Div. ( David Rizzieri, MD )
Study ID Numbers:	00005124
Study First Received:	December 21, 2007
Last Updated:	August 13, 2008
ClinicalTrials.gov Identifier:	NCT00586690
Health Authority:	United States: Food and Drug Administration

Keywords provided by Duke University:

Stem cell transplant
matched donor
NK infusion

Study placed in the following topic categories:

Lymphatic Diseases
Antibodies
Immunoproliferative Disorders

Lymphoproliferative Disorders
Lymphoma
Immunoglobulins

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Immune System Diseases

ClinicalTrials.gov processed this record on January 14, 2009