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

NCT05503134 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: KARMA
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Keywords

AML

Outcome Measures

Primary Outcomes (2)

• Incidence and severity of adverse events

  Up to 56 days after the first NK cell infusion

• Rate of dose limiting toxicities

  Up to 56 days after the first NK cell infusion

Secondary Outcomes (7)

• Minimal Residual Disease (MRD) negative response rate by flow cytometry

  At the end of Cycle 1 and Cycle 2 (each cycle is 28 days)

• CR rate after first cycle

  At the end of Cycle 1 (each cycle is 28 days)

• Relapse free survival and overall survival

  1 year

• Median time to neutrophil and platelet count recovery

  1 year

• Median duration of remission for patients who do not go onto transplant

  1 year

Other Outcomes (3)

• Immunophenotype of UD-NK cells

  Weekly samples from day 0 to day +28 after the first NK cell infusion for each cycle (each cycle is 28 days)

• Function of UD-NK Cells

  Day 0 of the first cycle

• Expansion/persistence of UD-NK cells after infusion

  Weekly samples from day 0 to day +28 after the first NK cell infusion for each cycle (each cycle is 28 days)

Study Arms (1)

Treatment

EXPERIMENTAL

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.

Biological: Universal Donor Natural Killer Cells

Interventions

Universal Donor Natural Killer Cells BIOLOGICAL

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

Treatment

Eligibility Criteria

• Age: 1 Year - 24 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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.

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
• 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).

Sponsors & Collaborators

• Nationwide Children's Hospital: lead

Study Sites (1)

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Margaret Lamb, MD

  Nationwide Children's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Melinda C Triplet

CONTACT

6147226039; Melinda.Triplet@nationwidechildrens.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2022
• First Posted: August 16, 2022
• Study Start: February 14, 2022
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: November 4, 2024

Record last verified: 2024-10

Locations

US (1)