Safety and Efficacy of Expanded, Universal Donor Natural Killer Cells for Relapsed/Refractory AML

Recruiting now · Phase 1/Phase 2

Conditions studied: Acute Myeloid Leukemia

In brief

This is a phase I/II dose escalation study designed to determine the safety and estimate the efficacy of UD-NK cells combined with FLA chemotherapy in patients age 1-24.99 with relapsed or refractory acute myeloid leukemia. PRIMARY OBJECTIVE: I. To determine the safety and recommended phase II dose of adoptive NK cell therapy using UD-NK cells in pediatric and young adult patients with relapsed/refractory AML. SECONDARY OBJECTIVES: I. To estimate the efficacy of UD- NK cells with FLA chemotherapy in pediatric and young adult patients with relapsed/refractory AML. EXPLORATORY OBJECTIVES: I. To determine the immunophenotype and function of UD-NK cells II. To characterize in vivo expansion of UD-NK cells III. To determine the persistence of UD-NK cells Six doses of universal donor mbIL-21 expanded NK cells (UD-NK) given thrice weekly for two weeks. Days may vary and NK cells can be given from days 0 to 21. Patients may receive up to 2 cycles of fludarabine/cytarabine (FLA) + NK cells (up to 12 NK cell infusions) if they do not achieve CR after cycle 1 or if necessary to bridge to transplant.

Key facts

Study ID: NCT05503134
Run by: Nationwide Children's Hospital
People needed: 20
Starts: 2022-02-14
Expected to finish: 2027-02-01
Last updated by the study team: 2024-11-04

Who can join

Age: 1 and older, up to 24. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Patients with relapsed or primary refractory AML, including:
Patients with relapsed AML (Any patient in first or subsequent relapse are eligible. Patients with relapse after HSCT are eligible)
Primary refractory AML defined as failure to achieve a complete response after 2 cycles of induction chemotherapy, including persistent MRD positivity
Patients with isolated CNS or extramedullary disease are eligible Note: a response monitoring plan must be developed a priori for subjects with extramedullary disease
Patient age 1-24.99 years old
Negative serum test to rule out pregnancy within 2 weeks prior to enrollment in females of childbearing potential
o Sexually active males and females of childbearing potential must agree to use a form of contraception considered effective and medically acceptable by the Investigator for 6 months after the last dose of chemotherapy and/or NK cell infusion
Negative serology for human immunodeficiency virus (HIV)
Both males and females and members of all races and ethnic groups are eligible
Organ function requirements:
Renal function: Creatinine ≤ 2 mg/dl OR creatinine clearance > 60 ml/min/1.73m2.
Liver function: Total bilirubin ≤ 2 mg/dl (unless Gilbert's syndrome), AST and ALT ≤ 5 times the upper limit of normal (unless related to leukemic involvement). Upper limit of normal should be determined by the institutional defined normal laboratory range.
Cardiac function: left ventricular ejection fraction ≥ 40% or shortening fraction ≥20%. May be eligible after cardiology clearance if qualitatively normal function or repeat measures are normal.
CNS: Patients with seizure disorder may be eligible if seizures well controlled
All prior treatment related non-hematologic toxicities must have resolved to ≤ Grade 2 prior to enrollment unless granted approval by study PI and/or Co-Is.
All patients and/or their legal guardians must be able to understand and willing to sign a written informed consent document

You may not qualify if…

AML directed therapies in the 2 weeks prior to beginning treatment on this protocol (except for hydroxyurea)
o Note: There is no waiting period required for patients having received intrathecal cytarabine, methotrexate and/or hydrocortisone
Patients on immunosuppressive therapy
o Patients must be off of all systemic immunosuppressive therapy for at least 2 weeks prior to enrollment with no evidence of recurrent GVHD
Patients with a history of donor lymphocyte infusion or cellular therapy within the last 30 days are not eligible for this study
Allogeneic SCT < 3 months prior to study enrollment
Any comorbidities that in the opinion of the investigator will preclude receiving study therapy
Performance status: Karnofsky or Lansky Performance Scale (PS) < 50
Uncontrolled infection, defined as an infection which has not resolved or does not show evidence of significant resolution after initiating appropriate therapy
o Asymptomatic viremia such as CMV, HPV, BK virus, HCV, etc. is NOT considered as an exclusion criterion
Uncontrolled arrhythmias or uncontrolled symptomatic cardiac disease
History of autoimmune disease
Active GVHD at the time of enrollment
Patients with a history of adoptive cell therapy are excluded unless at least 30 days from infusion and with evidence of recovery of normal hematopoiesis (ANC ≥ 500/μL, platelet count ≥ 50,000/μL).

Where it is running

Nationwide Children's Hospital — Columbus, Ohio, United States (enrolling)

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.