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

David Rizzieri, MD

Status and phase: Completed; Phase 1

Conditions: Lymphoma

Treatments: Procedure: Donor Apheresis; Device: NK Cell infusion using CD56 monoclonal antibody

Study type: Interventional

Funder types: Other

Identifiers

NCT00586690

Pro00005124

Details and patient eligibility

About

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.

Full 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.

Enrollment: 47 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

---

47 participants in 2 patient groups

NK Cell Infusion

Experimental group

Description:

Natural Killer (NK) Cell infusion using CD56 monoclonal antibody

Treatment:

Device: NK Cell infusion using CD56 monoclonal antibody

Donor Apheresis

Other group

Description:

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.

Treatment:

Procedure: Donor Apheresis