MT2014-25: Haplo NK With SQ IL-15 in Adult Relapsed or Refractory AML Patients
Condition: Acute Myelogenous Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: IL-15
Intervention description: Preparative Regimen:
Fludarabine 25 mg/m2 x 5 days start day -6 Cyclophosphamide 60 mg/kg x 2 days on day -5 and -4 (if < 4 months from prior transplant, omit day -4 dose)
IL-15 Activated Donor NK Cells:
The apheresis product (collected day -1) will be enriched for NK cells with the large-scale CliniMacs® device (Miltenyi) by depletion of CD3+ cells to remove T-lymphocytes and depletion of CD19+ cells to remove B-lymphocytes. The NK cell enriched product will be activated by overnight incubation with10 ng/ml IL-15 under GMP conditions and infused on day 0.
IL-15 to Facilitate NK Cell Survival and Expansion:
IL-15 at 2 mcg/kg subcutaneously (SC) beginning day +1, once a day for 5 days followed by a 2 day rest, and then once a day for 5 days for 10 doses total
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: AML; Relapsed; Refractory

Summary:

      A phase II trial of CD3/CD19 depleted, IL-15 activated, donor natural killer (NK) cells in
      adults and subcutaneous IL-15 given after a preparative regimen for the treatment of relapsed
      or refractory acute myelogenous leukemia (AML). The primary objective is to study the
      potential efficacy of NK cells and IL-15 to achieve complete remission while maintaining
      safety.
    

Eligibility criteria:

        Inclusion Criteria (Recipient):

          -  Meets ONE of the following disease criteria:

               1. Primary AML induction failure: no CR after 2 or more induction attempts

               2. Relapsed AML or Secondary AML (from MDS or treatment related): not in CR after 1
                  or more cycles of standard re-induction therapy

               3. AML relapsed > 2 months after transplant: No re-induction required, and no more
                  than 1 re-induction cycle is allowed.

               4. Relapsed AML for patients > 60 years of age the 1 cycle of standard chemotherapy
                  is not required if either of the following criteria is met:

                    -  Relapse within 6 months of last chemotherapy

                    -  BM blast count < 30% within 10 days of starting protocol therapy

          -  Available related HLA-haploidentical donor (aged 14 to 75 years) by at least Class I
             serologic typing at the A&B locus

          -  Karnofsky Performance Status ≥ 60%

          -  Patients must have adequate organ within 14 days (28 days for pulmonary and cardiac)
             of study registration

          -  Able to be off prednisone or other immunosuppressive medications for at least 3 days
             prior to NK cell infusion (excluding preparative regimen pre-medications).

          -  Agrees to use contraception prior to study entry and for the duration of study
             participation.

        Exclusion Criteria (Recipient):

          -  Bi-phenotypic acute leukemia.

          -  Transplant < 60 days prior to study enrollment.

          -  Active autoimmune disease.

          -  History of severe asthma

          -  Uncontrolled intercurrent illness

          -  New or progressive pulmonary infiltrates on screening chest x-ray or chest CT scan
             that has not been evaluated with bronchoscopy

          -  Pleural effusion large enough to be detectable on chest x-ray.

          -  Pregnant women

          -  History of HIV, active or chronic hepatitis B, hepatitis C or HTLV-I infection

          -  Known hypersensitivity to any of the study agents used

          -  Received investigational drugs within the 14 days of study registration.

          -  Known active CNS involvement.

        Criteria For Initial Donor Selection:

          -  Related donors (sibling, parent, offspring, parent or offspring of an HLA identical
             sibling).

          -  14-75 years of age.

          -  At least 40 kilogram body weight.

          -  In general good health as determined by the evaluating medical provider.

          -  HLA-haploidentical donor/recipient match by at least Class I serologic typing at the
             A&B locus.

          -  Not pregnant.

          -  Able and willing to undergo apheresis.