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NKX101, Intravenous Allogeneic Engineered Natural Killer Cells, in Adults With AML or MDS

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04623944
Recruitment Status : Recruiting
First Posted : November 10, 2020
Last Update Posted : May 17, 2021
Information provided by (Responsible Party):
Nkarta Inc.

Brief Summary:
This is a single arm, open-label, multi-center, Phase 1 study to determine safety and tolerability of an experimental therapy called NKX101 (allogeneic CAR NK cells targeting NKG2D ligands) in patients with relapsed/refractory AML or intermediate, high and very high risk relapsed/refractory MDS

Condition or disease Intervention/treatment Phase
Relapsed/Refractory AML AML, Adult MDS Refractory Myelodysplastic Syndromes Biological: NKX101 - CAR NK cell therapy Phase 1

Detailed Description:

This is a dose-finding study of NKX101 and will be conducted in 2 parts:

Part 1: dose finding with two dosing regimens, utilizing modified "3+3" enrollment schema.

Part 2: dose expansion to further evaluate safety and tolerability, cellular kinetics, pharmacodynamics and anti-tumor response in expansion cohorts of patients with either AML or MDS.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of NKX101, an Activating Chimeric Receptor Natural Killer Cell Therapy, in Subjects With Hematological Malignancies or Dysplasias
Actual Study Start Date : September 21, 2020
Estimated Primary Completion Date : July 2023
Estimated Study Completion Date : July 2038

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: NKX101 - CAR NK cell therapy

All subjects will receive fludarabine/cyclophosphamide lymphodepletion followed by 3 or 2 weekly doses of NKX101. Regimen A will dose on Day 0, 7, and 14 of a 28-day cycle. Regimen B will dose on Day 0 and 7 of a 28-day cycle.

Part 1: either haplo-matched related donor derived or unrelated off-the-shelf donor derived NKX101 will be used

Part 2: either haplo-matched related donor derived or unrelated off-the-shelf donor derived NKX101 will be used

Biological: NKX101 - CAR NK cell therapy
NKX101 is an investigational allogeneic CAR NK product targeting NKG2D ligands on cancer cells. The starting dose of NKX101 in Part 1/Regimen A is 1 × 10^8 NK cells (2 × 10^6/kg for patients < 50 kg) administered as 3 weekly doses. The starting dose of NKX101 in Part 1/Regimen B is 1.5 × 10^8 NK cells (3 × 10^6/kg for patients < 50 kg) administered as 2 weekly doses. Part 2 will use the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of NKX101 as determined in Part 1.
Other Names:
  • Cyclophosphamide
  • Fludarabine

Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 30 days after last dose of NKX101 ]
    Incidence, nature, and severity of treatment related adverse events will be evaluated. An adverse event is any unfavorable and unintended sign including clinically significant abnormal laboratory findings, symptom or disease.

  2. Proportion of subjects experiencing dose-limiting toxicities of NKX101 [ Time Frame: 28 days from first dose of NKX101 ]
    DLTs are defined as adverse events attributable to NKX101 treatment that occur during Cycle 1 and meet protocol-specified criteria

Secondary Outcome Measures :
  1. Assessment of NKX101 half-life [ Time Frame: 28 days from first dose of NKX101 ]
    Time required for 50% reduction from maximum amount of circulating NKX101

  2. NKX101 duration of persistence [ Time Frame: Followed up to 2 years after last dose of NKX101 ]
    Testing NKX101 in peripheral blood every 3 months after dosing to determine persistence

  3. Evaluation of host immune response against NKX101 [ Time Frame: Followed up to 2 years after last dose of NKX101 ]
    Serum samples will be measured for antibodies against NKX101

  4. Objective response rate to NKX101 [ Time Frame: Primary assessment: 28 days after first dose of NKX101 followed up to 2 years after last dose of NKX101 ]
    Percentage of subjects with complete and partial response. AML subjects will be assessed for anti-tumor activity of NKX101 based on the updated ELN criteria (Döhner 2017). Subjects with MDS will be assessed for anti-tumor activity of NKX101 based on the IWG criteria with MDS (Cheson 2006).

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • General:

    • ECOG performance status ≤2
    • Haplo-matched related subjects require a suitable haplo-matched related donor, who is able and willing to undergo leukapheresis
  • Disease related:

    • For AML subjects:

      • Previously treated relapsed/refractory AML, including subjects with MRD+ disease
      • White blood cell count of ≤25 × 10^9/L
    • For MDS subjects:

      • Intermediate-, high-, or very high-risk MDS
      • Previously treated relapsed/refractory MDS
  • Adequate Organ Function
  • Platelet count ≥30,000/uL (platelet transfusions acceptable)
  • Other:

    • Signed informed consent
    • Agree to use an effective barrier method of birth control

Exclusion Criteria:

  • Disease related:

    • Acute promyelocytic leukemia with t(15;17) (q22;q12); or abnormal promyelocytic leukemia/retinoic acid receptor alpha (APML-RARA)
    • Evidence of leukemic meningitis or known active central nervous system disease
    • Use of any anti-AML/MDS chemotherapeutic or targeted small molecule drug within protocol specified window prior to the first dose of NKX101
    • Presence of residual non-hematologic toxicity from prior therapies that has not resolved to ≤ Grade 1
    • Any hematopoietic cell transplantation within 16 weeks
  • Other comorbid conditions and concomitant medications prohibited as per study protocol
  • Other:

    • Pregnant or lactating female

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04623944

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Contact: Minoti Hiremath, MD, PhD +1 415-651-5080
Contact: Cornell Chang +1 415-651-5060

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United States, Colorado
Colorado Blood Cancer Institute Recruiting
Denver, Colorado, United States, 80218
Contact: Marcello Rotta    844-482-4812   
Principal Investigator: Marcello Rotta, MD         
United States, Georgia
Winship Cancer Institute, Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Tolu Adewuya    404-778-1900   
Principal Investigator: William Blumm, MD         
United States, Ohio
The Cleveland Clinic - Taussig Cancer Institute Recruiting
Cleveland, Ohio, United States, 44195
Contact: Navneet Majhail, MD   
Principal Investigator: Navneet Majhail, MD         
United States, Tennessee
Sarah Cannon at TriStar Bone Marrow Transplant Center Recruiting
Nashville, Tennessee, United States, 37203
Contact: Carlos Bachier    844-482-4812   
Principal Investigator: Carlos Bachier, MD         
United States, Texas
MD Anderson Cancer Center, University of Texas Recruiting
Houston, Texas, United States, 77030
Contact: Carol Bivins    713-794-4460   
Principal Investigator: Gautam Borthakur, MD         
Sponsors and Collaborators
Nkarta Inc.
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Study Director: Minoti Hiremath, MD, PhD Nkarta Inc.
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Responsible Party: Nkarta Inc. Identifier: NCT04623944    
Other Study ID Numbers: NKX101-101
First Posted: November 10, 2020    Key Record Dates
Last Update Posted: May 17, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Nkarta Inc.:
Natural killer
Interleukin 15
NK cell
Cell Therapy
Adoptive cell therapy
r/r AML
Additional relevant MeSH terms:
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Myelodysplastic Syndromes
Bone Marrow Diseases
Hematologic Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists