Description:
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)
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
NKX019-101
- NCT ID:
NCT05020678
Conditions
- 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
Interventions
Drug | Synonyms | Arms |
---|
NKX019 | | NKX019 - CAR NK cell therapy |
Purpose
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. 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.
Trial Arms
Name | Type | Description | Interventions |
---|
NKX019 - CAR NK cell therapy | Experimental | 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. | |
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] |
Time Frame: | 30 days after last dose of NKX019 |
Safety Issue: | |
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. |
Secondary Outcome Measures
Measure: | Assessment of NKX019 half-life |
Time Frame: | Time Frame: 28 days from first dose of NKX019 |
Safety Issue: | |
Description: | Time required for 50% reduction from maximum amount of circulating NKX019 |
Measure: | NKX019 duration of persistence |
Time Frame: | Followed up to 2 years after last dose of NKX019 |
Safety Issue: | |
Description: | Testing NKX019 in peripheral blood every 3 months after dosing to determine persistence |
Measure: | Evaluation of host immune response against NKX019 |
Time Frame: | Followed up to 2 years after last dose of NKX019 |
Safety Issue: | |
Description: | Serum samples will be measured for antibodies against NKX019 |
Measure: | Objective response rate to NKX019 |
Time Frame: | Primary assessment: 28 days after first dose of NKX019 followed up to 2 years after last dose of NKX019 |
Safety Issue: | |
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. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Nkarta Inc. |
Trial 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
Last Updated
August 25, 2021