Clinical trial NCT04623944: NKX101, Intravenous Allogeneic CAR NK Cells, in Adults With AML or MDS
Official title: A Phase 1 Study of NKX101, an Activating Chimeric Receptor Natural Killer Cell Therapy, in Subjects With Hematological Malignancies or Dysplasias
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Relapsed/Refractory AML
AML, Adult
MDS
Refractory Myelodysplastic Syndromes
Keywords: NKG2D
CAR
Allogeneic
Natural killer
ACR
NKX101
IL15
Interleukin 15
NK cell
Cell Therapy
Immunotherapy
Adoptive cell therapy
r/r AML
Off-the-shelf
Lead sponsor: Nkarta, Inc.
Sponsor class: INDUSTRY
First posted: 2020-11-10
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single-arm, open-label, multi-center, Phase 1 study to determine safety and tolerability of an experimental therapy called NKX101 (allogeneic CAR NK cells targeting NKG2D ligands) in patients with relapsed/refractory AML or intermediate, high and very high risk relapsed/refractory MDS.

Detailed description: This is a dose-finding study of NKX101 and will be conducted in 2 parts:

Part 1: dose finding with two dosing regimens, utilizing modified "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 either AML or MDS.

Eligibility criteria: Inclusion Criteria:

* General:

  * ECOG performance status ≤2
* Disease related:

  * For AML subjects:

    * Previously treated relapsed/refractory AML, including subjects with MRD+ disease
    * Received at most 3 lines of previous anti-leukemia therapy
    * For subjects with targetable fms-like tyrosine kinase 3 (FLT3)-mutated or isocitrate dehydrogenase (IDH)1/2 mutated disease, subjects must have received at least 1 prior respective targeted therapy and may receive up to 4 lines of prior therapy
    * White blood cell count of ≤25 × 10\^9/L
    * For groups receiving NKX101 after lymphodepletion with fludarabine/cyclophosphamide +/- decitabine: Disease localized to the bone marrow, as evidenced by ≤ 5% peripheral blasts and no evidence of extramedullary disease
    * For groups receiving NKX101 after lymphodepletion with fludarabine/ cyclophosphamide +/- decitabine, group receiving NKX101 after lymphodepletion with fludarabine/ara-C: Additional subjects with specifically high-risk genetic mutations may be enrolled. High risk genetic mutation per ELN 2022 should be evaluated as per local assay and discussed with the Sponsor prior to study entry
    * For groups receiving NKX101 after lymphodepletion with fludarabine/cyclophosphamide +/- decitabine, group receiving NKX101 after lymphodepletion with fludarabine/ara-C: Additional subjects who have relapsed following HCT may be enrolled.
  * For MDS subjects:

    * Intermediate-, high-, or very high-risk MDS
    * Previously treated relapsed/refractory MDS
    * Received at least 1 and at most 3 lines of previous standard anti-MDS therapy
    * For groups receiving NKX101 after lymphodepletion with fludarabine/ cyclophosphamide +/- decitabine: Additional subjects with specifically high-risk disease may be enrolled. High-risk genetic mutation should be evaluated as per local assay
    * For group receiving lymphodepletion with fludarabine/cyclophosphamide +/- decitabine and NKX101: Additional subjects who have relapsed following HCT may be enrolled.
* Adequate Organ Function
* Platelet count ≥30,000/uL (platelet transfusions acceptable)
* Other:

  * Signed informed consent
  * Agree to use an effective barrier method of birth control

Exclusion Criteria:

* Disease related:

  * Acute promyelocytic leukemia with t(15;17) (q22;q12); or abnormal promyelocytic leukemia/retinoic acid receptor alpha (APML-RARA) and AML arising from chronic myelomonocytic leukemia (CMML)
  * Evidence of leukemic meningitis or known active central nervous system disease
  * Peripheral leukocytosis with ≥ 20,000 blasts/μL or other evidence of rapidly progressive disease that would preclude subject from completing at least 1 cycle of treatment
  * Use of any anti-AML/MDS chemotherapeutic or targeted small molecule drug within protocol specified window prior to the first dose of NKX101
  * Presence of residual non-hematologic toxicity from prior therapies that has not resolved to ≤ Grade 1
  * Any hematopoietic cell transplantation within 16 weeks
* Other comorbid conditions and concomitant medications prohibited as per study protocol
* Other:

  * Pregnant or lactating female

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: 30 days after last dose of NKX101
measure: Response rate to NKX101 (for Part 2)
timeFrame: 28 days from first dose of NKX101
Secondary outcomes:
measure: Assessment of NKX101 half-life
timeFrame: 28 days from first dose of NKX101
measure: NKX101 duration of persistence
timeFrame: Followed up to 2 years after last dose of NKX101
measure: Evaluation of host immune response against NKX101
timeFrame: Followed up to 2 years after last dose of NKX101
measure: Response rate to NKX101
timeFrame: Primary assessment: 28 days after first dose of NKX101 followed up to 2 years after last dose of NKX101
Other outcomes:
Locations:
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Cleveland
country: United States
facility: The Cleveland Clinic - Taussig Cancer Institute
state: Ohio
city: Nashville
country: United States
facility: Sarah Cannon at TriStar Bone Marrow Transplant Center
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center, University of Texas
state: Texas
city: San Antonio
country: United States
facility: Methodist Healthcare System of San Antonio
state: Texas
Study officials:
affiliation: Nkarta, Inc.
name: David Shook, MD
role: STUDY_DIRECTOR
References: