Trial Testing Safety of IL-21 NK Cells for Induction of R/R AML

NCT ID: NCT04220684

Last Updated: 2026-01-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-11
• Study Completion Date: 2024-10-22

Brief Summary

This phase I trial studies the side effects of donor natural killer (NK) cell therapy in treating patients with acute myeloid leukemia that has come back (recurrent) or has not responded to treatment (refractory). Natural killer cells are a type of immune cell. Immunotherapy with genetically modified NK cells from donors may induce changes in the body's immune system and may interfere with the ability of cancer cells to grow and spread.

Detailed Description

PRIMARY OBJECTIVE:

I. To determine the safety of adoptive NK cell therapy using membrane-bound interleukin-21 (mbIL21)-expanded, off-the-shelf, third-party donor-derived NK cells in patients with relapsed/refractory acute myeloid leukemia (AML).

SECONDARY OBJECTIVES:

I. Estimate the complete response (CR, CR with incomplete hematologic recovery [CRi] & morphologic leukemia-free state [MLFS]).

II. Estimate the median relapse free survival. III. Estimate the median time to neutrophil and platelet count recovery. IV. Estimate the median duration of remission. V. Estimate the incidence of infectious complications. VI. Estimate percentage of patients receiving this regimen who are rendered transplant-eligible.

CORRELATIVE OBJECTIVES:

I. Determine the persistence of ex-vivo expanded, off-the-shelf, third-party NK cells.

II. Characterize in vivo expansion of third-party NK cells and if it differs based on the conditioning regimen as defined by NK chimerism assay.

III. Determine the immunophenotype and function of expanded cells. IV. Chimerism analysis in patients who have had post-transplant relapses.

OUTLINE: This is a dose-escalation study of membrane-bound interleukin-21-expanded haploidentical natural killer cells.

INDUCTION: Patients receive fludarabine intravenously (IV) and cytarabine IV on days -6 to -2 in the absence of disease progression or unacceptable toxicity.

COHORT II: Patients who are >= 60 years old, unable/unwilling to tolerate intensive chemotherapy, or disease insensitive to cytarabine (tp53, TET2 mutations) receive fludarabine IV on days -5 to -2 and decitabine IV on days -6 to -2 in the absence of disease progression or unacceptable toxicity.

All patients receive membrane-bound interleukin-21-expanded haploidentical natural killer cells via infusion on days 0, 2, 4, 7, 9, and 11.

After completion of study treatment, patients are followed up to day 56.

Conditions

Allogeneic Stem Cell Transplant Recipient; Blasts 10 Percent or More of Bone Marrow Nucleated Cells; Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Conditioning Regimen

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

Group Type: EXPERIMENTAL

Cytarabine Hydrochloride

Intervention Type: DRUG

Given IV

Fludarabine

Intervention Type: DRUG

Given IV

Induction

Six doses of third-party-donor mbIL-21 expanded (KDS-1001) cells given thrice weekly for two weeks. Days may vary and KDS-1001 can be given from days 0 to 21

Group Type: EXPERIMENTAL

Membrane-bound Interleukin-21-Expanded Haploidentical Natural Killer Cells

Intervention Type: BIOLOGICAL

Given via infusion

Interventions

Cytarabine Hydrochloride

Given IV

Intervention Type: DRUG

Fludarabine

Given IV

Intervention Type: DRUG

Membrane-bound Interleukin-21-Expanded Haploidentical Natural Killer Cells

Given via infusion

Intervention Type: BIOLOGICAL

Other Intervention Names

Ara-C HCl; Arabinosylcytosine Hydrochloride; Aracytidine Hydrochloride; CHX-3311; Cytosar Hydrochloride; Cytosine Arabinosine Hydrochloride; U-19920A; Fluradosa; (mbIL21)-expanded Haploidentical NK Cells; Donor mbIL21-expanded NK Cells; mbIL21-expanded Haploidentical NK Cells

Eligibility Criteria

Inclusion Criteria

• Primary Relapsed AML including
• Relapsed AML after allogeneic stem cells
• Isolated CNS or extramedullary disease (Note: a response monitoring plan must be developed a priori for subjects with extramedullary disease)
• 1-3 prior lines of therapy which includes chemotherapy, hypomethylating agents, venetoclax or targeted therapy.
• Patient weight ≥ 42 kg
• Performance status: Karnofsky or Lansky Performance Scale (PS) greater or equal to 70, or, ECOG score 0-2.
• Renal function: Serum creatinine ≤ 2 mg/dl and/or creatinine clearance greater or equal than 40 cc/min.
• Pulmonary function: FEV1, FVC and DLCO ≥ 50% of expected, corrected for hemoglobin.
• Liver function: Total bilirubin ≤ 2 mg/dl or ≤ 2.5 x ULN for age (unless Gilbert's syndrome) and SGPT (ALT) ≤ 2.5 x ULN for age.
• Cardiac function: left ventricular ejection fraction ≥ 40%.
• CNS: Patients with seizure disorder are eligible if seizures well controlled.
• Negative serum test to rule out pregnancy within 2 weeks prior to enrollment in females of childbearing potential (non-childbearing potential defined as premenarchal, greater than one year post-menopausal, or surgically sterilized).
• Sexually active males and females of childbearing potential must agree to use a form of contraception considered effective and medically acceptable by the Investigator.
• Ability to understand and willingness to sign the written informed consent document.
• Negative serology for human immunodeficiency virus (HIV).
• Patients on hydrocortisone for adrenal insufficiency or on inhaled or topical steroids are eligible.

Maintenance Phase: Patients that complete induction therapy and who achieve a CR/CRi/PR within the designated follow-up period and who are ineligible, unable or unwilling to undergo HSCT; these patients will not receive fludarabine or cytarabine.

Exclusion Criteria

• Investigational therapies in the 3 weeks prior to beginning treatment on this protocol.
• Patients receiving any concurrent therapy including but not limited to chemotherapy, targeted therapy, radiation therapy, or immunotherapy for R/R AML.
• Any comorbidities that in the opinion of the investigator will preclude receiving fludarabine or cytarabine.
• Uncontrolled arrhythmias or uncontrolled symptomatic cardiac disease.
• Active GVHD
• Prednisone dose is > 20 mg/day or >0.25mg/kg, whichever is higher will be excluded.
• Patients with donor-specific antibodies with MFI > 5000 will be ineligible

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kiadis Pharma

INDUSTRY

Sponsor Role: collaborator

Sumithira Vasu

OTHER

Sponsor Role: lead

Responsible Party

Sumithira Vasu

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Sumithira Vasu, MBBS

Role: PRINCIPAL_INVESTIGATOR

Ohio State University Comprehensive Cancer Center

Locations

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Oregon Health & Science University

Portland, Oregon, United States

Countries

United States

Provided Documents

Document Type: Informed Consent Form

View Document

Related Links

http://cancer.osu.edu

The Jamesline

Other Identifiers

NCI-2019-05150

Identifier Type: REGISTRY

Identifier Source: secondary_id

OSU-18336

Identifier Type: -

Identifier Source: org_study_id