This phase 2 clinical trial investigates the effectiveness of cytokine-induced memory-like natural killer (CIML NK) cells in combination with FLAG chemotherapy as a treatment for refractory or relapsed AML. Previous studies in adults with AML sowed successful induction of remission and a previous phase 1 study demonstrated that CIML NK cells can be used safely in pediatric patients. This phase 2 study uses FLAG chemotherapy to lower leukemic burden and suppress the recipient's immune system to provide an optimal environment for CIML NK cell expansion and anti-leukemic activity.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
-The CIML NK cells (maximum dose capped at 10 x 106/kg, minimum dose allowed is 0.5 x 106/kg) will be infused on Day 0 without a filter or pump.
-Fludarabine (dose: 30 mg/m\^2 per dose) will be given daily beginning on Day -7 for a total of 5 doses administered as an IV infusion over 30 minutes.
-Ara-C (dose: 2000mg/m\^2 per dose) will be given daily for a total of 5 doses administered as IV infusion over 3 hours, starting the same day as fludarabine.
Response rate (complete remission (CR) plus complete remission with incomplete blood count recovery (CRi))
* Complete remission (CR) requires all of the following: * Bone marrow: * Morphologically leukemia free state (≤ 5% myeloblasts) with normal maturation of all cell lines. Persistent dysplasia may be noted * Peripheral blood: * Platelets ≥ 100,000/uL * Neutrophils ≥ 1000/uL * Complete remission with incomplete blood count recovery (CRi): * All of the above criteria for CR must be met, except that absolute neutrophils \<1000/μL or platelets \<100,000 /μL in the blood.
Time frame: Day 28
Percentage of patients able to proceed to stem cell transplant
Time frame: Up to 60 days
Disease-free survival (DFS)
-DFS is defined as the time from the day CR or CRi is documented until disease progression or death.
Time frame: Up to 2 years
Overall survival (OS)
-OS is defined from the date of first dose of fludarabine on this study until death.
Time frame: Up to 2 years
Percentage of patients who achieve minimum residual disease (MRD)-negative status
Time frame: Day 28
Safety of regimen as measured by number of adverse events
-Adverse events will be collected from Day 0 to Day 35; however, bone marrow suppression (ANC ≤ 500/mcL) and adverse events of GVHD involving the liver, skin, or gastrointestinal tract will be recorded to Day 100
Time frame: From Day 0 to Day 100
Duration of remission
Time frame: Up to 2 years
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-Filgrastim (dose: 5 mcg/kg per dose to a maximum of 300 mcg) will be given subcutaneously daily for a total of 5 doses starting the same day as fludarabine and ara-C.
-IL-2 will be administered subcutaneously at a dose of 1 million units/m2 every other day from Day 0 to Day +12 (7 doses total).
-Donor only
Time to progression
Time frame: Up to 2 years