Clinical Trials /

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

NCT05020678

Description:

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)

Related Conditions:
  • B-Cell Acute Lymphoblastic Leukemia
  • B-Cell Non-Hodgkin Lymphoma
  • Chronic Lymphocytic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: NKX019-101
  • NCT ID: NCT05020678

Conditions

  • 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

Interventions

DrugSynonymsArms
NKX019NKX019 - CAR NK cell therapy

Purpose

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)

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. 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.
    

Trial Arms

NameTypeDescriptionInterventions
NKX019 - CAR NK cell therapyExperimentalAll subjects will receive fludarabine/cyclophosphamide lymphodepletion followed by 3 weekly doses of NKX019 on Day 0, 7, and 14 of a 28-day cycle.
  • NKX019

Eligibility Criteria

        Inclusion Criteria:

        General:

        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-directed therapy must have disease that remains CD19+

          -  Have measurable disease

          -  Have received ≥2 lines of therapy except subjects with MCL 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

          -  Adequate organ function

          -  White blood cell count of ≤20 × 109/L

          -  Platelet count ≥30,000/uL

        Exclusion Criteria:

        • Disease related:

          -  Burkitt Lymphoma, primary 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 LBCL
             expansion cohort who must have received prior CD19 directed 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame:30 days after last dose of NKX019
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Assessment of NKX019 half-life
Time Frame:Time Frame: 28 days from first dose of NKX019
Safety Issue:
Description:Time required for 50% reduction from maximum amount of circulating NKX019
Measure:NKX019 duration of persistence
Time Frame:Followed up to 2 years after last dose of NKX019
Safety Issue:
Description:Testing NKX019 in peripheral blood every 3 months after dosing to determine persistence
Measure:Evaluation of host immune response against NKX019
Time Frame:Followed up to 2 years after last dose of NKX019
Safety Issue:
Description:Serum samples will be measured for antibodies against NKX019
Measure:Objective response rate to NKX019
Time Frame:Primary assessment: 28 days after first dose of NKX019 followed up to 2 years after last dose of NKX019
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Nkarta Inc.

Trial Keywords

  • 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

Last Updated

August 25, 2021