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
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)
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 Phase
Phase 1
Study Type
Interventional
Primary Outcome
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Secondary Outcome
Assessment of NKX019 half-life
Condition
Lymphoma, Non-Hodgkin
Intervention
NKX019
Study Arms / Comparison Groups
NKX019 - CAR NK cell therapy
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
150
Start Date
August 20, 2021
Completion Date
December 2038
Primary Completion Date
December 2023
Eligibility 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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
David Shook, MD, +1 415-651-5080, [email protected]
Location Countries
Australia
Location Countries
Australia
Administrative Informations
NCT ID
NCT05020678
Organization ID
NKX019-101
Responsible Party
Sponsor
Study Sponsor
Nkarta Inc.
Study Sponsor
David Shook, MD, Study Director, Nkarta Inc.
Verification Date
January 2023