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.
Study 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)
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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
Primary outcome measure(s)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] — 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.
Proportion of subjects experiencing dose-limiting toxicities of NKX019 — 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
Objective response rate to NKX019 in Part 2 — 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.
Trial sites (6)
Facility
City
Region
Status
Colorado Blood Cancer Institute
Denver
Colorado
The Cleveland Clinic Foundation
Cleveland
Ohio
Institute of Haematology, Royal Prince Alfred Hospital
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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