Safety Trial of NK DLI From 6/6 HLA Matched Family Member Following Nonmyeloablative ASCT
Condition: Lymphoma
Intervention: NK Cell infusion using CD56 monoclonal antibody; Donor Apheresis
Intervention description: The cells from leukapheresis will be natural killer (NK) cell 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 acute graft versus host disease (aGVHD) at the time of infusion. Patients will be evaluated for toxicity and response until 20 weeks after the last NK Infusion.; 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.
Intervention MeSH terms: Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 47.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Stem cell transplant; matched donor; NK infusion

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.
    

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