Haploidentical Natural Killer Cells to Treat Refractory or Relapsed Acute Myelogenous Leukemia (AML)
Condition: Leukemia, Myelogenous, Acute
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Natural Killer Cells; Fludarabine; Cyclophosphamide; Denileukin diftitox; Donor lymphapheresis; IL-2
Intervention description: Given by infusion on Day 0. The product is T cell-depleted (CD3-) and B cell-depleted (CD19). Target dose for infusion is < or = 8 x 10^7 nucleated cells/kilogram.; Administered as a 1 hour intravenous infusion once a day for 5 doses beginning on day -6.; Administered as a 2 hour intravenous infusion with high volume fluid flush and mesna per institutional guidelines on day -5 and -4 one hour after fludarabine infusion. (Day -4 administration may be omitted if patient has had a transplant in the previous 4 months.); 12 ug/kg/day will be administered on day -1 and day -2 intravenously.; Day -1 before planned NK cell infusion, the donor will undergo lymphapheresis (Removal of lymphocytes from donated blood, with the remainder of the blood retransfused into the donor).; Administered after NK cell infusion, 10 million units every other day for a total of 6 doses. (Patients weighing less than 45 kilograms will receive a dose of 5 million units/m^2 every other day for 6 doses).
Intervention MeSH terms: Cyclophosphamide; Fludarabine; Interleukin-2; Denileukin diftitox
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 2 Years
Healthy volunteers: No
Keywords: acute myelogenous leukemia; primary acute myelogenous leukemia; secondary acute myelogenous leukemia; relapsed acute myelogenous leukemia

Summary:

      This is a phase II therapeutic study of related donor HLA-haploidentical NK-cell based
      therapy after a high dose of fludarabine/cyclophosphamide with denileukin diftitox
      preparative regimen for the treatment of poor prognosis acute myelogenous leukemia (AML).
    

Eligibility criteria:

        Inclusion Criteria:

          -  ≥ 2 years of age

          -  Meets one of the following disease criteria:

               -  Primary acute myelogenous leukemia (AML) induction failure: no complete remission
                  (CR) after 2 or more induction attempts

               -  Relapsed acute myelogenous leukemia (AML): not in CR after 1 or more cycles of
                  standard re-induction therapy. 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

                    -  blast count < 30% within 10 days of starting protocol therapy

               -  Secondary AML from myelodysplastic syndrome (MDS)

               -  AML relapsed > 2 months after transplant who do not have the option of donor
                  lymphocyte infusions (e.g. recipients of autologous or umbilical cord blood [UCB]
                  transplants) Patients with prior central nervous system (CNS) involvement are
                  eligible provided that it has been treated and CSF is clear for at least 2 weeks
                  or magnetic resonance imaging (MRI) stable prior to enrollment. CNS therapy
                  (chemotherapy or radiation) should continue as medically indicated during the
                  study treatment.

          -  Available related HLA-haploidentical donor (3-5 of 6 HLA-A, B and C)

          -  Karnofsky Performance Status > 50% or Lansky Play score > 50

          -  Adequate organ function defined as:

               -  Creatinine: ≤ 2.0 mg/dL (for pediatric patients - ClCr > 50 ml/min or age
                  adjusted Cr)

               -  Hepatic: Liver function tests (LFT's) < 5 x upper limit of institutional normal
                  (ULN)

               -  Pulmonary Function: oxygen saturation ≥ 90% on room air and pulmonary function
                  >50% corrected Diffusion lung capacity for carbon monoxide (DLCO) and Forced
                  expiratory volume in one second (FEV1) Oxygen saturation [>92%] can be used in
                  child where pulmonary function tests (PFT's) cannot be obtained. (Testing
                  required only if symptomatic or prior known impairment.)

               -  Cardiac Function: Ejection fraction (EF) ≥ 40%, no uncontrolled angina, severe
                  uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
                  ischemia or active conduction system abnormalities

          -  Able to be off prednisone or other immunosuppressive medications for at least 3 days
             prior to natural killer (NK) cell infusion (excluding denileukin diftitox pre-meds)

          -  Women of child bearing potential must have a negative pregnancy test within 14 days
             prior to study registration and agree to use adequate birth control during study
             treatment.

          -  Voluntary written consent

        Exclusion Criteria:

          -  Bi-phenotypic acute leukemia

          -  Transplant < 60 days prior to study enrollment

          -  New or progressive pulmonary infiltrates on screening chest x-ray or chest computated
             tomography (CT) scan that has not been evaluated with bronchoscopy, if feasible.
             Infiltrates attributed to infection must be stable/improving (with associated clinical
             improvement) after 1 week of appropriate therapy (4 weeks for presumed or documented
             fungal infections). Surgical resection waives any waiting requirements.

          -  Uncontrolled bacterial or viral infections - chronic asymptomatic viral hepatitis is
             allowed

          -  Pleural effusion large enough to be detectable on chest x-ray

          -  Known hypersensitivity to any of the study agents used

          -  Received investigational drugs within the 14 days before enrollment

          -  Known active CNS involvement