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

NCT04220684 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-18336NCI-2019-05150
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Keywords

Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) of membrane-bound interleukin-21-expanded haploidentical natural killer (NK) cells

  The MTD will be defined as the highest safely tolerated dose where at most one patient in six experiences dose-limiting toxicity (DLT) during DLT observation period. DLT is defined as any steroid refractory acute graft versus host disease.

  Up to 63 days

• Incidence of adverse events

  Toxicities will be assessed by type and grade using Common Terminology Criteria for Adverse Events version 5.0 and displayed in summary form by cohort and overall. Toxicities will be summarized and reported regardless of attribution and also only those attributed to NK cells.

  Up to day 28

Secondary Outcomes (8)

• Complete response (CR)

  Up to day 56

• CR with incomplete hematologic recovery

  Up to day 56

• Morphologic leukemia-free state

  Up to day 56

• Median relapse free survival

  Up to day 56

• Median time to neutrophil and platelet count recovery

  Up to day 56

Other Outcomes (3)

• Identification of In-vivo expansion of NK cells

  Up to day 56

• Chimerism analysis to determine origin and number of circulating NK cells

  Up to day 56

• Number of donor human leukocyte antigen (HLA) detection

  Up to day 56

Study Arms (2)

Conditioning Regimen

EXPERIMENTAL

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

Drug: Cytarabine Hydrochloride; Drug: Fludarabine

Induction

EXPERIMENTAL

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

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

Interventions

Cytarabine Hydrochloride DRUG

Given IV

Also known as: Ara-C HCl, Arabinosylcytosine Hydrochloride, Aracytidine Hydrochloride, CHX-3311, Cytosar Hydrochloride, Cytosine Arabinosine Hydrochloride, U-19920A

Conditioning Regimen

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Conditioning Regimen

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

Given via infusion

Also known as: (mbIL21)-expanded Haploidentical NK Cells, Donor mbIL21-expanded NK Cells, mbIL21-expanded Haploidentical NK Cells

Induction

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Sumithira Vasu: lead
• Kiadis Pharma: collaborator

Study Sites (2)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Oregon Health & Science University

Portland, Oregon, 24344, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Cytarabine; fludarabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Sumithira Vasu, MBBS

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 26, 2019
• First Posted: January 7, 2020
• Study Start: June 11, 2020
• Primary Completion: October 22, 2024
• Study Completion: October 22, 2024
• Last Updated: January 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)