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

Chronic Lymphocytic Leukemia Clinical Trial

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 Details — Status: Recruiting

Administrative data

• NCT number: NCT05020678
• Other study ID #: NKX019-101
• Status: Recruiting
• Phase: Phase 1
• Start date: August 20, 2021
• Est. completion date: December 2038

Study information

• Verified date: March 2024
• Source: Nkarta Inc.
• Contact: Nishi Kothari, MD
• Phone: +1 415-651-5080
• Email: medmonitor[@]nkartatx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 2038
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Aggression
• Aggressive Lymphoma
• B-cell Acute Lymphoblastic Leukemia
• Chronic Lymphocytic Leukemia
• Indolent Lymphoma
• Large B-cell Lymphoma
• Large-cell Lymphoma
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Lymphoma
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Mantle Cell Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Small Lymphocytic Lymphoma
• Waldenstrom Macroglobulinemia

Intervention

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.

Locations

Country	Name	City	State
Australia	Royal Brisbane and Woman's Hospital	Brisbane	Queensland
Australia	Institute of Haematology, Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Peter MacCallum Cancer Center	Melbourne	Victoria
Australia	St. Vincent's Hospital	Sydney	New South Wales
United States	University of Chicago	Chicago	Illinois
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	Colorado Blood Cancer Institute	Denver	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
Nkarta Inc.

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Proportion of subjects experiencing dose-limiting toxicities of NKX019	DLTs are defined as adverse events attributable to NKX019 treatment that occur during Cycle 1 and meet protocol-specified criteria	28 days from first dose of NKX019
Primary	Objective response rate to NKX019 in Part 2	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.	Primary assessment: 28 days after the first dose of NKX019 followed up to 2 years after the last dose of NKX019]
Secondary	Assessment of NKX019 half-life	Time required for 50% reduction from maximum amount of circulating NKX019	Time Frame: 28 days from first dose of NKX019
Secondary	NKX019 duration of persistence	Testing NKX019 in peripheral blood every 3 months after dosing to determine persistence	Followed up to 2 years after last dose of NKX019
Secondary	Evaluation of host immune response against NKX019	Serum samples will be measured for antibodies against NKX019	Followed up to 2 years after last dose of NKX019
Secondary	Objective response rate to NKX019 in Part 1	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.	Primary assessment: 28 days after first dose of NKX019 followed up to 2 years after last dose of NKX019