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NKX019, Intravenous Allogeneic Chimeric Antigen Receptor Natural Killer Cells (CAR NK), in Adults With B-cell Cancers

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ClinicalTrials.gov Identifier: NCT05020678
Recruitment Status : Recruiting
First Posted : August 25, 2021
Last Update Posted : September 5, 2023
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 the safety and tolerability of an experimental therapy called NKX019 (allogeneic CAR NK cells targeting CD19) in patients with relapsed/refractory non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) or B cell acute lymphoblastic leukemia (B-ALL)

Condition or disease Intervention/treatment Phase
Lymphoma, Non-Hodgkin B-cell Acute Lymphoblastic Leukemia Large B-cell Lymphoma Mantle Cell Lymphoma Indolent Lymphoma Waldenstrom Macroglobulinemia Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Aggressive Lymphoma Large-cell Lymphoma Biological: NKX019 Phase 1

Detailed Description:

This is a dose-finding study of NKX019 and will be conducted in 2 parts:

Part 1: dose finding utilizing a "3+3" enrollment schema and safety lead-in to confirm dose for NKX019 in combination with rituximab expansion cohorts (as applicable) Part 2: dose expansion to further evaluate safety and tolerability, cellular kinetics, pharmacodynamics and anti-tumor response in expansion cohorts of patients with large B cell lymphoma (LBCL), mantle cell lymphoma (MCL), indolent lymphoma (IL), Waldenström macroglobulinemia (WM), CLL/ small lymphocytic lymphoma (SLL), and B-ALL.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of NKX019, a CD19 Chimeric Antigen Receptor Natural Killer (CAR NK) Cell Therapy, in Subjects With B-cell Malignancies
Actual Study Start Date : August 20, 2021
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2038

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: NKX019 - CAR NK cell therapy
All subjects will receive fludarabine/cyclophosphamide lymphodepletion followed by 3 weekly doses of NKX019 on Day 0, 7, and 14 of a 28-day cycle. Combination cohorts (if opened) will additionally receive rituximab with each cycle.
 Biological: NKX019
NKX019 is an investigational allogeneic CAR NK product targeting CD19 on cells. The starting dose of NKX019 in Part 1 is 3 × 10^8 NK cells (6 × 10^6/kg for patients < 50 kg) administered as 3 weekly doses. Part 2 (dose expansion cohorts) will use the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of NKX019 as determined in Part 1.


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 NKX019 ]
    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 NKX019 [ Time Frame: 28 days from first dose of NKX019 ]
    DLTs are defined as adverse events attributable to NKX019 treatment that occur during Cycle 1 and meet protocol-specified criteria

  3. Objective response rate to NKX019 in Part 2 [ Time Frame: Primary assessment: 28 days after the first dose of NKX019 followed up to 2 years after the last dose of NKX019] ]
    Percentage of subjects with complete and partial response. Response to treatment will be assessed based on: Lugano classification with LYRIC refinement for subjects with NHL (except CLL/SLL and WM); 2018 iwCLL guidelines for subjects with CLL/SLL; Version 1.2020 NCCN for subjects with B-ALL; consensus criteria from the 6th International Workshop on Waldenström Macroglobulinemia for subjects with WM.


Secondary Outcome Measures :
  1. Assessment of NKX019 half-life [ Time Frame: Time Frame: 28 days from first dose of NKX019 ]
    Time required for 50% reduction from maximum amount of circulating NKX019

  2. NKX019 duration of persistence [ Time Frame: Followed up to 2 years after last dose of NKX019 ]
    Testing NKX019 in peripheral blood every 3 months after dosing to determine persistence

  3. Evaluation of host immune response against NKX019 [ Time Frame: Followed up to 2 years after last dose of NKX019 ]
    Serum samples will be measured for antibodies against NKX019

  4. Objective response rate to NKX019 in Part 1 [ Time Frame: Primary assessment: 28 days after first dose of NKX019 followed up to 2 years after last dose of NKX019 ]
    Percentage of subjects with complete and partial response. Response to treatment will be assessed based on: Lugano classification with LYRIC refinement for subjects with NHL (except CLL/SLL and WM); 2018 iwCLL guidelines for subjects with CLL/SLL; Version 1.2020 NCCN for subjects with B-ALL; consensus criteria from the 6th International Workshop on Waldenström Macroglobulinemia for subjects with WM.


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:

Eastern Cooperative Oncology Group (ECOG) performance status ≤1

• Disease Related:

  • Have a histologically or cytologically confirmed diagnosis of r/r B cell NHL or CLL or B-ALL as defined by WHO 2016 classification
  • Subjects who received prior CD19/CD20-directed therapy must have disease that remains CD19+ and/or CD20+ respectively
  • Have measurable disease
  • Have received ≥2 lines of therapy except subjects with MCL, CAR T Naïve cohorts and WM, who must have received at least 1 prior line of therapy
  • Have received a combination of an anti CD20 monoclonal antibody and cytotoxic chemotherapy for subjects with NHL

  • Received:

    • BTKi for subjects with MCL, CLL/SLL, WM, and other indications where a BTKi is approved
    • Venetoclax for subjects with CLL/SLL
    • Tyrosine kinase inhibitor for subjects with Philadelphia chromosome (Ph+) B-ALL
  • Not responded or relapsed within 12 months of completion of their prior line of therapy, with the exception of a newly diagnosed Richter's transformation of CLL/SLL or other transformation of an indolent lymphoma, including from WM
  • Subjects must not have evidence of rapidly progressive disease that would preclude subject from completing at least 1 cycle of treatment.
  • Adequate organ function
  • White blood cell count of ≤20 × 109/L
  • Platelet count ≥30,000/uL

Exclusion Criteria:

• Disease related:

  • Burkitt Lymphoma, primary central nervous system (CNS) lymphoma, Richter's transformation to Hodgkin lymphoma
  • Subjects with WM who underwent plasmapheresis <35 days prior to the first dose of NKX019
  • Subjects with NHL with any evidence of active CNS malignancy
  • Subjects with B-ALL who have extramedullary disease (EMD)
  • Subjects with any prior cellular therapy except subjects enrolling in selected cohorts who must have received prior CAR T therapy, recent HCT, or complications from HCT
  • Recent use of any cancer-directed therapy within protocol specified window prior to the first dose of NKX019
  • Residual toxicities ≥Grade 2 due to prior therapy
  • Other comorbid conditions and concomitant medications prohibited as per study protocol
  • 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): NCT05020678


Contacts
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Contact: David Shook, MD +1 415-651-5080 medmonitor@nkartatx.com
Contact: Beth Martello +1 415-651-5060 clinops@nkartatx.com

Locations
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United States, Colorado
Colorado Blood Cancer Institute Recruiting
Denver, Colorado, United States, 80218
Contact: Michael Tees, MD    720-754-4800      
Contact: Savannah Harris    +1-720-754-8063    Savannah.Harris@SarahCannon.com   
Principal Investigator: Michael Tees, MD         
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Peter Riedell, MD       peter.riedell@uchicagomedicine.org   
Principal Investigator: Peter Riedell, MD         
United States, Ohio
The Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44195
Contact: Brian Hill, MD PhD    216-445-9451    hillb2@ccf.org   
Principal Investigator: Brian Hill, MD PhD         
Australia, New South Wales
Institute of Haematology, Royal Prince Alfred Hospital Recruiting
Camperdown, New South Wales, Australia, 2050
Contact: Christian Bryant, MBSS PhD    +61 2 9515 8031    Christian.Bryant@health.nsw.gov.au   
Principal Investigator: Christain Bryant, MBSS PhD         
St. Vincent's Hospital Recruiting
Sydney, New South Wales, Australia, 2010
Contact: Louise Christophersen    +61 2 9355 5702    louise.christophersen@svha.org.au   
Principal Investigator: Nada Hamad, MBSS BSc         
Australia, Queensland
Royal Brisbane and Woman's Hospital Recruiting
Brisbane, Queensland, Australia, 4029
Contact: Glen W Kennedy, MBBS FRACP    +61 07 3646 7962    glen.kennedy@health.qld.gov.au   
Principal Investigator: Glen Kennedy, MBSS FRACP         
Australia, Victoria
Peter MacCallum Cancer Center Recruiting
Melbourne, Victoria, Australia, 3000
Contact: Parkville Cancer Clinical Trials Unit    +61 3 8559 7456    clinicaltrials.enquiries@petermac.org   
Principal Investigator: Michael Dickinson, MBSS DMedSci         
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: NCT05020678    
Other Study ID Numbers: NKX019-101
First Posted: August 25, 2021    Key Record Dates
Last Update Posted: September 5, 2023
Last Verified: August 2023
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.:
CD19
CAR
Allogeneic
Natural killer
ACR
NKX019
IL15
Interleukin 15
NK cell
Cell Therapy
Immunotherapy
 Adoptive cell therapy
r/r NHL
r/r B-ALL
r/r MCL
r/r IL
r/r WM
r/r CLL
r/r SLL
Aggressive lymphoma
Indolent lymphoma
LCL
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Waldenstrom Macroglobulinemia
Lymphoma, Non-Hodgkin
Aggression
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
 Leukemia, Lymphoid
Leukemia, B-Cell
Chronic Disease
Disease Attributes
Pathologic Processes
Behavioral Symptoms
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders