Haploidentical Donor Natural Killer Cell Infusion With IL-15 in Acute Myelogenous Leukemia (AML)

This is an interventional treatment trial for Acute Myelogenous Leukemia focused on measuring acute myelogenous leukemia, natural killer cells, haploidentical donor Read More

Inclusion Criteria:

• ≥ 18 years of age

• Meets one of the following disease criteria:

  • Primary acute myelogenous leukemia (AML) induction failure: no complete response (CR )after 2 or more induction attempts
  • Relapsed AML or Secondary AML (from MDS or treatment-related): not in CR after 1 or more cycles of standard induction therapy. For patients > 60 years of age the 1 cycle of standard chemotherapy is not required if either of the following is met:
• relapse within 6 months of last chemotherapy

• blast count <30% within 10 days of starting protocol

  • 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 cerebrospinal fluid (CSF) is clear for at least 2 weeks 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%

• Adequate organ function defined as:

  • Creatinine: ≤ 2.0 mg/dL
  • Hepatic: Liver function tests (LFT's) < 5 times upper limit of institutional normal (ULN)
  • Pulmonary Function: oxygen saturation ≥ 90% on room air and pulmonary function >50% corrected DLCO and FEV1 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 preparative regimen pre-medications)
• Women of child bearing potential and men with partners of child bearing potential must agree to use effective contraception during therapy and for 4 months after completion of therapy.
• Voluntary written consent

Exclusion Criteria:

• Bi-phenotypic acute leukemia
• Transplant < 60 days prior to study enrollment
• Pregnant or breastfeeding - The agents used in this study include those that fall under Pregnancy Category D - have known teratogenic potential. Women of child bearing potential must have a negative pregnancy test within 14 days of study treatment start
• Active autoimmune disease
• History of severe asthma, presently on chronic medications (a history of mild asthma not requiring therapy is eligible)
• New or progressive pulmonary infiltrates on screening chest x-ray or chest 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

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 (low resolution)
• Not pregnant
• Agree to undergo donor viral screening panel
• Able and willing to undergo apheresis
• Voluntary written consent