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

NCT ID: NCT05020678

Last Updated: 2024-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-08-20

Study Completion Date

2038-12-31

Brief Summary

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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

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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.

Conditions

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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

Keywords

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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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

NKX019

Intervention Type BIOLOGICAL

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.

Interventions

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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.

Intervention Type BIOLOGICAL

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Nkarta, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David Shook, MD

Role: STUDY_DIRECTOR

Nkarta, Inc.

Locations

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Colorado Blood Cancer Institute

Denver, Colorado, United States

Site Status

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Institute of Haematology, Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Site Status

St. Vincent's Hospital

Sydney, New South Wales, Australia

Site Status

Royal Brisbane and Woman's Hospital

Brisbane, Queensland, Australia

Site Status

Peter MacCallum Cancer Center

Melbourne, Victoria, Australia

Site Status

Countries

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United States Australia

Other Identifiers

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NKX019-101

Identifier Type: -

Identifier Source: org_study_id