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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

TREATMENT

Phase

PHASE1

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

Condition: Lymphoma, Non-Hodgkin, B-cell Acute Lymphoblastic Leukemia and more
BIOLOGICAL: NKX019
Sydney, New South Wales, Australia and more
Sponsor: Nkarta, Inc.

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

Are you running this trial? If you're a clinic or sponsor, you can claim this study. Claim or learn more.

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

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/Arm	Intervention/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 Measure	Primary Outcome Description	Primary 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 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
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 outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
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
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
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
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

Frequently Asked Questions

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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