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NKX101, Intravenous Allogeneic CAR NK 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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04623944
Recruitment Status : Active, not recruiting
First Posted : November 10, 2020
Last Update Posted : April 9, 2024
Sponsor:
Information provided by (Responsible Party):
Nkarta Inc.

Study Description
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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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 61 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 2024
Estimated Study Completion Date : July 2039

Resource links provided by the National Library of Medicine


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

All subjects in Part 1 will receive lymphodepletion with fludarabine/cyclophosphamide followed by 3 or 2 (Regimen A or B, respectively) weekly doses of NKX101.

Subjects in Part 2 will receive lymphodepletion with either fludarabine/cyclophosphamide or fludarabine/cytarabine (ara-C), or if the optional arm is opened, lymphodepletion with fludarabine/cyclophosphamide and decitabine, followed by 3 weekly doses of NKX101.

Part 2: 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. 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
  • Cytarabine (ara-C)
  • Decitabine


Outcome Measures
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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. Response rate to NKX101 (for Part 2) [ Time Frame: 28 days from first dose of NKX101 ]
    Responses will be assessed per modified ELN criteria and will include complete and partial remission with and without varying degrees of hematologic recovery


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. 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 ]
    Time-to-first response, time-to-best response, duration of response, transfusion independent rate, bridge-to-transplant rate, event-free survival, progression-free survival (PFS), overall survival (OS) (for all subjects), and hematologic improvement rates (for subjects with myelodysplastic syndrome [MDS])


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

Inclusion Criteria:

  • General:

    • ECOG performance status ≤2

  • Disease related:

    • For AML subjects:

      • Previously treated relapsed/refractory AML, including subjects with MRD+ disease
      • Received at most 3 lines of previous anti-leukemia therapy
      • For subjects with targetable fms-like tyrosine kinase 3 (FLT3)-mutated or isocitrate dehydrogenase (IDH)1/2 mutated disease, subjects must have received at least 1 prior respective targeted therapy and may receive up to 4 lines of prior therapy
      • White blood cell count of ≤25 × 10^9/L
      • For groups receiving NKX101 after lymphodepletion with fludarabine/cyclophosphamide +/- decitabine: Disease localized to the bone marrow, as evidenced by ≤ 5% peripheral blasts and no evidence of extramedullary disease
      • For groups receiving NKX101 after lymphodepletion with fludarabine/ cyclophosphamide +/- decitabine, group receiving NKX101 after lymphodepletion with fludarabine/ara-C: Additional subjects with specifically high-risk genetic mutations may be enrolled. High risk genetic mutation per ELN 2022 should be evaluated as per local assay and discussed with the Sponsor prior to study entry
      • For groups receiving NKX101 after lymphodepletion with fludarabine/cyclophosphamide +/- decitabine, group receiving NKX101 after lymphodepletion with fludarabine/ara-C: Additional subjects who have relapsed following HCT may be enrolled.

    • For MDS subjects:

      • Intermediate-, high-, or very high-risk MDS
      • Previously treated relapsed/refractory MDS
      • Received at least 1 and at most 3 lines of previous standard anti-MDS therapy
      • For groups receiving NKX101 after lymphodepletion with fludarabine/ cyclophosphamide +/- decitabine: Additional subjects with specifically high-risk disease may be enrolled. High-risk genetic mutation should be evaluated as per local assay
      • For group receiving lymphodepletion with fludarabine/cyclophosphamide +/- decitabine and NKX101: Additional subjects who have relapsed following HCT may be enrolled.
  • 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) and AML arising from chronic myelomonocytic leukemia (CMML)
    • Evidence of leukemic meningitis or known active central nervous system disease
    • Peripheral leukocytosis with ≥ 20,000 blasts/μL or other evidence of rapidly progressive disease that would preclude subject from completing at least 1 cycle of treatment
    • 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
Contacts and Locations
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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 ClinicalTrials.gov identifier (NCT number): NCT04623944


Locations
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United States, Colorado
Colorado Blood Cancer Institute
Denver, Colorado, United States, 80218
United States, Florida
Mayo Clinic Florida
Jacksonville, Florida, United States, 32224
United States, Georgia
Winship Cancer Institute, Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
University of Chicago Medical Center
Chicago, Illinois, United States, 60637
United States, Ohio
The Cleveland Clinic - Taussig Cancer Institute
Cleveland, Ohio, United States, 44195
United States, Tennessee
Sarah Cannon at TriStar Bone Marrow Transplant Center
Nashville, Tennessee, United States, 37203
United States, Texas
MD Anderson Cancer Center, University of Texas
Houston, Texas, United States, 77030
Methodist Healthcare System of San Antonio
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Nkarta Inc.
Investigators
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Study Director: David Shook, MD Nkarta Inc.
More Information
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Responsible Party: Nkarta Inc.
ClinicalTrials.gov Identifier: NCT04623944    
Other Study ID Numbers: NKX101-101
First Posted: November 10, 2020    Key Record Dates
Last Update Posted: April 9, 2024
Last Verified: April 2024
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.:
NKG2D
CAR
Allogeneic
Natural killer
ACR
NKX101
IL15
 Interleukin 15
NK cell
Cell Therapy
Immunotherapy
Adoptive cell therapy
r/r AML
Off-the-shelf
Additional relevant MeSH terms:
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Myelodysplastic Syndromes
Bone Marrow Diseases
Hematologic Diseases
Cytarabine
Cyclophosphamide
Fludarabine
Decitabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
 Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors