QUILT-3.033: Haplo NK With SQ ALT-803 for Adults With Relapsed or Refractory AML
Condition: Acute Myeloid Leukemia
MeSH terms: Leukemia
Intervention: ALT-803
Intervention description: Preparative Regimen:
Fludarabine 25 mg/m2 x 5 days start day -6 Cyclophosphamide 60 mg/kg x 2 days on day -5 and -4
ALT-803 Stimulated Donor NK Cells:
The apheresis product (collected day -1) will be enriched for NK cells with the large-scale CliniMacs® device (Miltenyi) by depletion of CD3+ cells to remove T-lymphocytes and depletion of CD19+ cells to remove B-lymphocytes. The NK cell enriched product will be stimulated by overnight incubation with 36.1 ng/mL ALT-803 under GMP conditions and infused on day 0.
ALT-803 to Facilitate NK Cell Survival and Expansion:
ALT-803 at 10 mcg/kg subcutaneously (SC) with the 1st dose administered on day 0 (no sooner than 4 hours post NK cells), day +5 and day +10 for 3 doses total
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: Accepts Healthy Volunteers

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