NKX101, Intravenous Allogeneic CAR NK Cells, in Adults With AML or MDS

NCT ID: NCT04623944

Last Updated: 2024-12-27

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-21
• Study Completion Date: 2039-07-31

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

NKX101 - CAR NK cell therapy

All subjects in Part 1 will receive lymphodepletion with fludarabine/cyclophosphamide followed by 3 or 2 (Regimen A or B, respectively) weekly doses of NKX101.

Subjects in Part 2 will receive lymphodepletion with either fludarabine/cyclophosphamide or fludarabine/cytarabine (ara-C), or if the optional arm is opened, lymphodepletion with fludarabine/cyclophosphamide and decitabine, followed by 3 weekly doses of NKX101.

Part 2: unrelated off-the-shelf donor derived NKX101 will be used.

Group Type: EXPERIMENTAL

NKX101 - CAR NK cell therapy

Intervention Type: BIOLOGICAL

NKX101 is an investigational allogeneic CAR NK product targeting NKG2D ligands on cancer cells. Part 2 will use the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of NKX101 as determined in Part 1.

Interventions

NKX101 - CAR NK cell therapy

NKX101 is an investigational allogeneic CAR NK product targeting NKG2D ligands on cancer cells. Part 2 will use the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of NKX101 as determined in Part 1.

Intervention Type: BIOLOGICAL

Other Intervention Names

Cyclophosphamide; Fludarabine; Cytarabine (ara-C); Decitabine

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nkarta, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Shook, MD

Role: STUDY_DIRECTOR

Nkarta, Inc.

Locations

Colorado Blood Cancer Institute

Denver, Colorado, United States

Mayo Clinic Florida

Jacksonville, Florida, United States

Winship Cancer Institute, Emory University

Atlanta, Georgia, United States

University of Chicago Medical Center

Chicago, Illinois, United States

The Cleveland Clinic - Taussig Cancer Institute

Cleveland, Ohio, United States

Sarah Cannon at TriStar Bone Marrow Transplant Center

Nashville, Tennessee, United States

MD Anderson Cancer Center, University of Texas

Houston, Texas, United States

Methodist Healthcare System of San Antonio

San Antonio, Texas, United States

Countries

United States

Other Identifiers

NKX101-101

Identifier Type: -

Identifier Source: org_study_id