MDS Clinical Trial
Official title:
A Phase 1 Study of NKX101, an Activating Chimeric Receptor Natural Killer Cell Therapy, in Subjects With Hematological Malignancies or Dysplasias
Verified date | April 2024 |
Source | Nkarta Inc. |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Active, not recruiting |
Enrollment | 61 |
Est. completion date | July 2039 |
Est. primary completion date | July 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
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 | Colorado Blood Cancer Institute | Denver | Colorado |
United States | MD Anderson Cancer Center, University of Texas | Houston | Texas |
United States | Mayo Clinic Florida | Jacksonville | Florida |
United States | Sarah Cannon at TriStar Bone Marrow Transplant Center | Nashville | Tennessee |
United States | Methodist Healthcare System of San Antonio | San Antonio | Texas |
Lead Sponsor | Collaborator |
---|---|
Nkarta Inc. |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | |
Primary | 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 | Assessment of NKX101 half-life | Time required for 50% reduction from maximum amount of circulating NKX101 | 28 days from first dose of NKX101 | |
Secondary | NKX101 duration of persistence | Testing NKX101 in peripheral blood every 3 months after dosing to determine persistence | Followed up to 2 years after last dose of NKX101 | |
Secondary | Evaluation of host immune response against NKX101 | Serum samples will be measured for antibodies against NKX101 | Followed up to 2 years after last dose of NKX101 | |
Secondary | Response rate to NKX101 | Time-to-first response, time-to-best response, duration of response, transfusion independent rate, bridge-to-transplant rate, event-free survival, progression-free survival (PFS), overall survival (OS) (for all subjects), and hematologic improvement rates (for subjects with myelodysplastic syndrome [MDS]) | Primary assessment: 28 days after first dose of NKX101 followed up to 2 years after last dose of NKX101 |
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