Back to resultsNKX019, Intravenous Allogeneic Chimeric Antigen Receptor Natural Killer Cells (CAR NK), in Adults With B-cell Cancers
Primary Purpose
Lymphoma, Non-Hodgkin, B-cell Acute Lymphoblastic Leukemia, Large B-cell Lymphoma
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
NKX019
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoma, Non-Hodgkin focused on measuring 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
Eligibility Criteria
Inclusion Criteria:
General:
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-directed therapy must have disease that remains CD19+
- Have measurable disease
- Have received ≥2 lines of therapy except subjects with MCL 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
- Adequate organ function
- White blood cell count of ≤20 × 109/L
- Platelet count ≥30,000/uL
Exclusion Criteria:
• Disease related:
- Burkitt Lymphoma, primary 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 LBCL expansion cohort who must have received prior CD19 directed 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
Sites / Locations
- Colorado Blood Cancer InstituteRecruiting
- University of ChicagoRecruiting
- The Cleveland Clinic FoundationRecruiting
- Institute of Haematology, Royal Prince Alfred HospitalRecruiting
- St. Vincent's HospitalRecruiting
- Royal Brisbane and Woman's HospitalRecruiting
- Peter MacCallum Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
NKX019 - CAR NK cell therapy
Arm 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.
Outcomes
Primary Outcome Measures
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.
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
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.
Secondary Outcome Measures
Assessment of NKX019 half-life
Time required for 50% reduction from maximum amount of circulating NKX019
NKX019 duration of persistence
Testing NKX019 in peripheral blood every 3 months after dosing to determine persistence
Evaluation of host immune response against NKX019
Serum samples will be measured for antibodies against 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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05020678
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 20, 2021 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2038 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nkarta Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
150 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
NKX019 - CAR NK cell therapy
Arm Type
Experimental
Arm 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.
Intervention Type
Biological
Intervention Name(s)
NKX019
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Description
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.
Time Frame
30 days after last dose of NKX019
Title
Proportion of subjects experiencing dose-limiting toxicities of NKX019
Description
DLTs are defined as adverse events attributable to NKX019 treatment that occur during Cycle 1 and meet protocol-specified criteria
Time Frame
28 days from first dose of NKX019
Title
Objective response rate to NKX019 in Part 2
Description
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.
Time Frame
Primary assessment: 28 days after the first dose of NKX019 followed up to 2 years after the last dose of NKX019]
Secondary Outcome Measure Information:
Title
Assessment of NKX019 half-life
Description
Time required for 50% reduction from maximum amount of circulating NKX019
Time Frame
Time Frame: 28 days from first dose of NKX019
Title
NKX019 duration of persistence
Description
Testing NKX019 in peripheral blood every 3 months after dosing to determine persistence
Time Frame
Followed up to 2 years after last dose of NKX019
Title
Evaluation of host immune response against NKX019
Description
Serum samples will be measured for antibodies against NKX019
Time Frame
Followed up to 2 years after last dose of NKX019
Title
Objective response rate to NKX019 in Part 1
Description
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.
Time Frame
Primary assessment: 28 days after first dose of NKX019 followed up to 2 years after last dose of NKX019
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
David Shook, MD
Phone
+1 415-651-5080
Email
medmonitor@nkartatx.com
First Name & Middle Initial & Last Name or Official Title & Degree
Beth Martello
Phone
+1 415-651-5060
Email
clinops@nkartatx.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Shook, MD
Organizational Affiliation
Nkarta Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Colorado Blood Cancer Institute
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael Tees, MD
Phone
720-754-4800
First Name & Middle Initial & Last Name & Degree
Savannah Harris
Phone
+1-720-754-8063
Email
Savannah.Harris@SarahCannon.com
First Name & Middle Initial & Last Name & Degree
Michael Tees, MD
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peter Riedell, MD
Email
peter.riedell@uchicagomedicine.org
First Name & Middle Initial & Last Name & Degree
Peter Riedell, MD
Facility Name
The Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brian Hill, MD PhD
Phone
216-445-9451
Email
hillb2@ccf.org
First Name & Middle Initial & Last Name & Degree
Brian Hill, MD PhD
Facility Name
Institute of Haematology, Royal Prince Alfred Hospital
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christian Bryant, MBSS PhD
Phone
+61 2 9515 8031
Email
Christian.Bryant@health.nsw.gov.au
First Name & Middle Initial & Last Name & Degree
Christain Bryant, MBSS PhD
Facility Name
St. Vincent's Hospital
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Louise Christophersen
Phone
+61 2 9355 5702
Email
louise.christophersen@svha.org.au
First Name & Middle Initial & Last Name & Degree
Nada Hamad, MBSS BSc
Facility Name
Royal Brisbane and Woman's Hospital
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Glen W Kennedy, MBBS FRACP
Phone
+61 07 3646 7962
Email
glen.kennedy@health.qld.gov.au
First Name & Middle Initial & Last Name & Degree
Glen Kennedy, MBSS FRACP
Facility Name
Peter MacCallum Cancer Center
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3000
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Parkville Cancer Clinical Trials Unit
Phone
+61 3 8559 7456
Email
clinicaltrials.enquiries@petermac.org
First Name & Middle Initial & Last Name & Degree
Michael Dickinson, MBSS DMedSci
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
NKX019, Intravenous Allogeneic Chimeric Antigen Receptor Natural Killer Cells (CAR NK), in Adults With B-cell Cancers
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