study drug (Ontak) no longer available

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).

Patients achieving a complete remission and neutrophil recovery (ANC > 500) for at least 4 weeks will be considered for allogeneic transplant to prolong remission (independent of this study).

All patients, including those who go on to transplant, will be followed to determine disease free survival, treatment related mortality, and time to relapse.

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