Adoptive Transfer of Haploidentical Natural Killer Cells to Treat Refractory or Relapsed AML MT2010-02
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