QUILT-3.033: Haplo NK With SQ ALT-803 for Adults With Relapsed or Refractory AML

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