quilt-3.033: haplo nk with sq alt-803 for adults with relapsed or refractory aml

Conditions: Acute Myeloid Leukemia

Summary: this is a multi-institutional simon's optimal two-stage phase ii trial of cd3/cd19 depleted, alt-803 activated, haploidentical donor nk cells and subcutaneous alt-803 given after lymphodepleting chemotherapy (cy/flu) for the treatment of refractory or released acute myelogenous leukemia (aml).


Eligibility criteria:
inclusion criteria: * diagnosis of acute myeloid leukemia (aml) and meets one of the following disease criteria: * primary induction failure: * de novo aml - no cr after 2 or more chemotherapy induction attempts * secondary aml (from mds or treatment related): no cr after 1 or more chemotherapy induction attempts * relapse after chemotherapy: not in cr after 1, 2, or 3 re-induction attempts * patients \> 60 years of age, the 1 cycle of chemotherapy is not required * relapse after hematopoietic stem cell transplant: * relapse must have occurred \> 18 months after transplant * no re-induction required and no more than 1 re-induction attempt is allowed * notes: 1. for hypomethylating agents (i.e. decitabine, azacitidine) to count as an induction/re-induction attempt, the patient must have completed a minimum of 3 monthly cycles 2. for targeting agents (i.e. sorafenib) to count as an induction/re-induction attempt, the patient must have completed a minimum of 1 month without attaining cr 3. 7+3 followed by 5+2 counts as two induction attempts 4. use of hydroxyurea is permitted to control blasts until day -3 per section 8.7 5. a history of aml related cns involvement is allowed if csf analysis is negative on 2 test dates at least 2 weeks apart prior to study treatment. the use of ongoing cns maintenance therapy is allowed while on study. * hla-haploidentical related donor (aged 12 to 75 years) with donor/recipient match based on a minimum of intermediate resolution dna based class i typing of the a and b locus (at least 2/4 class i allele) * karnofsky performance status ≥ 60% * adequate organ function within 14 days of study registration (28 days for pulmonary and cardiac) defined as: * creatinine: ≤ 2.0 mg/dl * hepatic: ast and alt \< 3 x upper limit of institutional normal * pulmonary function: oxygen saturation ≥ 90% on room air; pft's required only if symptomatic or prior known impairment - must have pulmonary function \>50% corrected dlco and fev1. * cardiac function: lvef ≥ 40% by echocardiography, muga or cardiac mri, 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 systemic immunosuppressive medications for at least 3 days prior to nk cell infusion (excluding preparative regimen pre-medications) . * sexually active females of child bearing potential and males 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 prior to the performance of any research related procedures. exclusion criteria: * acute leukemias of ambiguous lineage * 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 at screening * active autoimmune disease requiring systemic immunosuppressive therapy * history of severe asthma and currently on systemic chronic medications (mild asthma requiring inhaled steroids only is eligible) * new or progressive pulmonary infiltrates on screening chest x-ray or chest ct scan unless cleared for study by pulmonary. 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). * uncontrolled bacterial, fungal or viral infections including hiv-1/2 or active hepatitis c/b - chronic asymptomatic viral hepatitis is allowed * received any investigational agent within the 14 days before the start of study treatment (1st dose of fludarabine) * prior alt-803