Clinical trial NCT00586690: Safety Trial of NK DLI From 6/6 HLA Matched Family Member Following Nonmyeloablative ASCT
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphoma
Keywords: Stem cell transplant
matched donor
NK infusion
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2008-01-04
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Toxicity
timeFrame: 5 months
Secondary outcomes:
measure: Efficacy - Progression Free Survival
timeFrame: 3 years
measure: Efficacy - Overall Survival
timeFrame: 8 years
measure: Efficacy - Disease Progression
timeFrame: 3 years
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
Study officials:
affiliation: Duke Health
name: David Rizzieri, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.