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

Safety Trial of Natural Killer (NK) Cell Donor Lymphocyte Infusions (DLI) From 3-5/6 Human Leukocyte Antigen (HLA) Matched Family Member Following Nonmyeloablative Allogeneic Stem Cell Transplantation (ASCT)

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 mismatched donors. This pilot study will evaluate toxicity including mortality, occurrence of acute graft versus host disease (aGVHD) and other severe toxicity.

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Device: NK-CD56

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 from mismatched donors.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Health Systems

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with who have undergone a non-myeloablative allogeneic transplant, using a 3-5/6 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 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: NK-CD56; NK Cell infusion using CD56 monoclonal antibody following nonmyeloablative SCT from mismatched donors

Device: NK-CD56; NK Cell infusion using CD56 monoclonal antibody following nonmyeloablative 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity	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.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy - Overall Survival	Evaluate the efficacy of the regimen in terms of overall survival (OS).	7 years

Collaborators and Investigators

• Sponsor: David Rizzieri, MD
• Investigators: Principal Investigator: David Rizzieri, MD, Duke University Health Systems

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: December 21, 2007
• First Submitted That Met QC Criteria: December 21, 2007
• First Posted (Estimate): January 4, 2008

Study Record Updates

• Last Update Posted (Estimate): June 12, 2014
• Last Update Submitted That Met QC Criteria: June 6, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Stem cell transplant; mismatched donor; NK infusion
• Other Study ID Numbers: Pro00005123