Register a trial

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05020678




Registration number
NCT05020678
Ethics application status
Date submitted
20/08/2021
Date registered
25/08/2021

Titles & IDs
Public title
NKX019, Intravenous Allogeneic Chimeric Antigen Receptor Natural Killer Cells (CAR NK), in Adults With B-cell Cancers
Scientific title
A Phase 1 Study of NKX019, a CD19 Chimeric Antigen Receptor Natural Killer (CAR NK) Cell Therapy, in Subjects With B-cell Malignancies
Secondary ID [1] 0 0
NKX019-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lymphoma, Non-Hodgkin 0 0
B-cell Acute Lymphoblastic Leukemia 0 0
Large B-cell Lymphoma 0 0
Mantle Cell Lymphoma 0 0
Indolent Lymphoma 0 0
Waldenstrom Macroglobulinemia 0 0
Chronic Lymphocytic Leukemia 0 0
Small Lymphocytic Lymphoma 0 0
Aggressive Lymphoma 0 0
Large-cell Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Mental Health 0 0 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - NKX019

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.


Treatment: Other: 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 code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Timepoint [1] 0 0
30 days after last dose of NKX019
Primary outcome [2] 0 0
Proportion of subjects experiencing dose-limiting toxicities of NKX019
Timepoint [2] 0 0
28 days from first dose of NKX019
Primary outcome [3] 0 0
Objective response rate to NKX019 in Part 2
Timepoint [3] 0 0
Primary assessment: 28 days after the first dose of NKX019 followed up to 2 years after the last dose of NKX019]
Secondary outcome [1] 0 0
Assessment of NKX019 half-life
Timepoint [1] 0 0
Time Frame: 28 days from first dose of NKX019
Secondary outcome [2] 0 0
NKX019 duration of persistence
Timepoint [2] 0 0
Followed up to 2 years after last dose of NKX019
Secondary outcome [3] 0 0
Evaluation of host immune response against NKX019
Timepoint [3] 0 0
Followed up to 2 years after last dose of NKX019
Secondary outcome [4] 0 0
Objective response rate to NKX019 in Part 1
Timepoint [4] 0 0
Primary assessment: 28 days after first dose of NKX019 followed up to 2 years after last dose of NKX019

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/08/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2038
Actual
Sample size
Target
150
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Institute of Haematology, Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
St. Vincent's Hospital - Sydney
Recruitment hospital [3] 0 0
Royal Brisbane and Woman's Hospital - Brisbane
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Center - Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2010 - Sydney
Recruitment postcode(s) [3] 0 0
4029 - Brisbane
Recruitment postcode(s) [4] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Ohio

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Nkarta, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
David Shook, MD
Address 0 0
Nkarta, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Nishi Kothari, MD
Address 0 0
Country 0 0
Phone 0 0
+1 415-651-5080
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05020678