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

NCT04623944 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: NKX101-101
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 8

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.

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

Outcome Measures

Primary Outcomes (2)

• 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.

  30 days after last dose of NKX101

• Response rate to NKX101 (for Part 2)

  Responses will be assessed per modified ELN criteria and will include complete and partial remission with and without varying degrees of hematologic recovery

  28 days from first dose of NKX101

Secondary Outcomes (4)

• Assessment of NKX101 half-life

  28 days from first dose of NKX101

• NKX101 duration of persistence

  Followed up to 2 years after last dose of NKX101

• Evaluation of host immune response against NKX101

  Followed up to 2 years after last dose of NKX101

• Response rate to NKX101

  Primary assessment: 28 days after first dose of NKX101 followed up to 2 years after last dose of NKX101

Study Arms (1)

NKX101 - CAR NK cell therapy

EXPERIMENTAL

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.

Biological: NKX101 - CAR NK cell therapy

Interventions

NKX101 - CAR NK cell therapy 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.

Also known as: Cyclophosphamide, Fludarabine, Cytarabine (ara-C), Decitabine

NKX101 - CAR NK cell therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nkarta, Inc.: lead

Study Sites (8)

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

The Cleveland Clinic - Taussig Cancer Institute

Cleveland, Ohio, 44195, United States

Location

Sarah Cannon at TriStar Bone Marrow Transplant Center

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center, University of Texas

Houston, Texas, 77030, United States

Location

Methodist Healthcare System of San Antonio

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Cyclophosphamide; fludarabine; Cytarabine; Decitabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Azacitidine; Aza Compounds; Ribonucleosides

Study Officials

• David Shook, MD

  Nkarta, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2020
• First Posted: November 10, 2020
• Study Start: September 21, 2020
• Primary Completion: October 2, 2024
• Study Completion (Estimated): July 1, 2039
• Last Updated: December 27, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)