Clinical trial NCT04354025: Cytokine-induced Memory-like NK Cells in Combination With Chemotherapy in Pediatric Patents With Refractory or Relapsed AML
Official title: A Phase 2 Study of Cytokine-induced Memory-like NK Cells in Combination With Chemotherapy in Pediatric Patients With Refractory or Relapsed AML
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Refractory Acute Myeloid Leukemia
Relapsed Acute Myeloid Leukemia
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2020-04-21
Enrollment: 0
Sex: ALL
Minimum age (years): 1
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Refractory AML without complete remission (CR) after induction therapy (primary induction failure) or relapsed AML after obtaining a CR. Disease defined by one of the following:

  \*≥ 5% blasts in the bone marrow (M2/M3 bone marrow), with or without extramedullary disease

  \*absolute blast count greater than 1,000 per microliter in the peripheral blood with or without extramedullary disease.
* Age requirement for pediatric cohort: 1-21 years of age.
* Available HLA-haploidentical donor that meets the following criteria:

  * Related donor (parent, sibling, offspring, or offspring of sibling)
  * At least 18 years of age
  * HLA-haploidentical donor/recipient match by at least Class I serologic typing at the A\&B locus.
  * In general, good health and medically able to tolerate leukapheresis required for harvesting the NK cells for this study.
  * Negative for hepatitis, HTLV, and HIV on donor viral screen
  * Not pregnant
  * Voluntary written consent to participate in this study
* Patients with known CNS involvement with AML are eligible provided that they have been treated and CSF is clear for at least 2 weeks prior to enrollment into the study. CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment.
* Karnofsky/Lansky performance status \> 50 %
* Adequate organ function as defined below:

  * Total bilirubin \< 2 mg/dL
  * AST(SGOT)/ALT(SGPT) \< 3.0 x upper limit of normal (ULN)
  * Creatinine within normal institutional limits OR creatinine clearance \> 50 mL/min/1.73 m2 by Schwartz formula or GFR (See Appendix B)
  * Oxygen saturation ≥90% on room air
  * Ejection fraction ≥35%
* Able to be off corticosteroids and any other immune suppressive medications beginning on Day -3 and continuing until 30 days after the infusion of the CIML NK cells. However, use of low-level corticosteroids is permitted if deemed medically necessary. Low-level corticosteroid use is defined as 10mg or less of prednisone (or equivalent for other steroids) per day.
* Women of childbearing potential must have a negative pregnancy test within 28 days prior to study registration. Female and male patients (along with their female partners) must agree to use two forms of acceptable contraception, including one barrier method, during participation in the study and throughout the DLT evaluation period.
* Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

* Relapsed after allogeneic transplantation.
* Isolated extramedullary relapse
* Circulating blast count \>30,000/µL by morphology or flow cytometry (cytoreductive therapies including leukapheresis or hydroxyurea are allowed).
* Patients with any of the following diagnoses:

  * Down's syndrome
  * Acute promyelocytic leukemia (APL)
  * Juvenile myelomonocytic leukemia (JMML)
* Uncontrolled bacterial or viral infections, or known HIV, Hepatitis B or C infection.
* Known hypersensitivity to one or more of the study agents.
* Received any investigational drugs within the 14 days prior to the first dose of fludarabine.
* Pregnant

Primary outcomes:
measure: Response rate (complete remission (CR) plus complete remission with incomplete blood count recovery (CRi))
timeFrame: Day 28
measure: Percentage of patients able to proceed to stem cell transplant
timeFrame: Up to 60 days
Secondary outcomes:
measure: Disease-free survival (DFS)
timeFrame: Up to 2 years
measure: Overall survival (OS)
timeFrame: Up to 2 years
measure: Percentage of patients who achieve minimum residual disease (MRD)-negative status
timeFrame: Day 28
measure: Safety of regimen as measured by number of adverse events
timeFrame: From Day 0 to Day 100
measure: Duration of remission
timeFrame: Up to 2 years
measure: Time to progression
timeFrame: Up to 2 years
Other outcomes:
Locations:
Study officials:
affiliation: Washington University School of Medicine
name: Jeffrey Bednarski, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: