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

PHASE1RECRUITING

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).

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Study details:

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.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  • Eastern Cooperative Oncology Group (ECOG) performance status ≤1
  • 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
  • Received: Venetoclax for subjects with CLL/SLL
  • Received: 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

  • 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
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    Eligibility

    Age eligible for study : 18 and older

    Healthy volunteers accepted : No

    Gender eligible for study: All

    Things to know

    Study dates

    Study start: 2021-08-20

    Primary completion: 2024-08-01

    Study completion finish: 2038-12-01

    study type

    Study type

    TREATMENT

    phase

    Phase

      PHASE1

    trial

    Trial ID

    NCT05020678

    Intervention or treatment

    BIOLOGICAL: NKX019

    Conditions

    • Lymphoma, Non-Hodgkin
    • B-cell Acute Lymphoblastic Leukemia
    • Large B-cell Lymphoma
    • Mantle Cell Lymphoma
    • Chronic Lymphocytic Leukemia
    • Small Lymphocytic Lymphoma
    • Indolent Lymphoma
    • Waldenstrom Macroglobulinemia
    • Aggressive Lymphoma
    • Large-cell Lymphoma
    Image related to Lymphoma, Non-Hodgkin
    • Condition: Lymphoma, Non-Hodgkin, B-cell Acute Lymphoblastic Leukemia and more

    • BIOLOGICAL: NKX019

    • Sydney, New South Wales, Australia and more

    • Sponsor: Nkarta, Inc.

    Find a site

    Closest Location:

    St. Vincent's Hospital

    Research sites nearby

    Select from list below to view details:

    • St. Vincent's Hospital

      Sydney, New South Wales, Australia

    • Peter MacCallum Cancer Center

      Melbourne, Victoria, Australia

    • Institute of Haematology, Royal Prince Alfred Hospital

      Camperdown, New South Wales, Australia

    • Royal Brisbane and Woman's Hospital

      Brisbane, Queensland, Australia

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    Study Plan

    This section provides details of the study plan, including how the study is designed and what the study is measuring.

    How is the study designed?

    Participant Group/ArmIntervention/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.

    What is the study measuring?

    Primary outcome

    Primary Outcome MeasurePrimary Outcome DescriptionPrimary Outcome Time Frame
    Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]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.30 days after last dose of NKX019
    Proportion of subjects experiencing dose-limiting toxicities of NKX019DLTs are defined as adverse events attributable to NKX019 treatment that occur during Cycle 1 and meet protocol-specified criteria28 days from first dose of NKX019
    Objective response rate to NKX019 in Part 2Percentage 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.Primary assessment: 28 days after the first dose of NKX019 followed up to 2 years after the last dose of NKX019]

    Secondary outcome

    Secondary Outcome MeasureSecondary Outcome DescriptionSecondary Outcome Time Frame
    Assessment of NKX019 half-lifeTime required for 50% reduction from maximum amount of circulating NKX019Time Frame: 28 days from first dose of NKX019
    NKX019 duration of persistenceTesting NKX019 in peripheral blood every 3 months after dosing to determine persistenceFollowed up to 2 years after last dose of NKX019
    Evaluation of host immune response against NKX019Serum samples will be measured for antibodies against NKX019Followed up to 2 years after last dose of NKX019
    Objective response rate to NKX019 in Part 1Percentage 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.Primary assessment: 28 days after first dose of NKX019 followed up to 2 years after last dose of NKX019

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    References

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

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