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

Lymphoma Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00586703
• Other study ID #: Pro00005123
• Status: Completed
• Phase: Phase 1
• First received: December 21, 2007
• Last updated: June 6, 2014
• Start date: April 2005
• Est. completion date: November 2013

Study information

• Verified date: May 2014
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: November 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma

Intervention

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.

Locations

Country	Name	City	State
United States	Duke University Health Systems	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
David Rizzieri, MD

Country where clinical trial is conducted

United States, 

References & Publications (1)

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/ — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Efficacy - Overall Survival	Evaluate the efficacy of the regimen in terms of overall survival (OS).	7 years	No