Recruiting
Phase 1
Phase 2

Natural Killer Cells

Sponsor:

Nationwide Children's Hospital

Code:

NCT05503134

Conditions

Acute Myeloid Leukemia

Eligibility Criteria

Sex: All

Age: 1 - 24

Healthy Volunteers: Not accepted

Interventions

Universal Donor Natural Killer Cells

Study Details

Brief summary:

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.

Conditions

Acute Myeloid Leukemia

Study ID

NCT05503134

Start date

Feb 14, 2022

Status verified date

Oct, 2024

Completion date

Feb, 2027

Anticipated

Primary completion date

Feb, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 1 - 24

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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).

Study Design

Enrollment

20 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment

Fludarabine 30 mg/m2/day (day -6 to day -2) and Cytarabine 2000 mg/ m2/day (days -6 to day -2)

Six doses of universal donor IL-21 expanded NK cells (UD-NK) given thrice weekly for two weeks starting on day 0. 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.

Interventions

Universal Donor Natural Killer Cells

Six doses of UD-NK cells will be given thrice weekly for two weeks for up to 2 cycles of treatment

Primary outcome measure

  • Incidence and severity of adverse events [ Time Frame: Up to 56 days after the first NK cell infusion ]
  • Rate of dose limiting toxicities [ Time Frame: Up to 56 days after the first NK cell infusion ]

Central Contacts and Locations

Locations

Nationwide Children's Hospital

Recruiting

Columbus, Ohio, United States, 43205

Contacts

More Information

Sponsor

Nationwide Children's Hospital

Last update posted

Nov 4, 2024

Last verified

Oct, 2024

Keywords

  • AML

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Nationwide Children's Hospital on 2024-11-04.