NKX101, Intravenous Allogeneic CAR NK Cells, in Adults With AML or MDS
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|ClinicalTrials.gov Identifier: NCT04623944|
Recruitment Status : Recruiting
First Posted : November 10, 2020
Last Update Posted : April 15, 2022
|Condition or disease||Intervention/treatment||Phase|
|Relapsed/Refractory AML AML, Adult MDS Refractory Myelodysplastic Syndromes||Biological: NKX101 - CAR NK cell therapy||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||90 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Study of NKX101, an Activating Chimeric Receptor Natural Killer Cell Therapy, in Subjects With Hematological Malignancies or Dysplasias|
|Actual Study Start Date :||September 21, 2020|
|Estimated Primary Completion Date :||July 2023|
|Estimated Study Completion Date :||July 2038|
Experimental: NKX101 - CAR NK cell therapy
All subjects in Part 1 will receive fludarabine/cyclophosphamide lymphodepletion followed by 3 or 2 (Regimen A or B, respectively) weekly doses of NKX101.
Subjects in Part 2 will receive either fludarabine/cyclophosphamide lymphodepletion or, if an AML combination arm is opened, fludarabine/cytarabine (ara-C), followed by 3 or 2 weekly doses of NKX101 depending on specific expansion cohort.
Regimen A will have 3 doses of NKX101 on Day 0, 7, and 14 of a 28-day cycle. Regimen B will have 2 doses of NKX101 on Day 0 and 7 of a 28-day cycle.
Part 1 and 2: either haplo-matched related donor derived or unrelated off-the-shelf donor derived NKX101 will be used.
Biological: NKX101 - CAR NK cell therapy
NKX101 is an investigational allogeneic CAR NK product targeting NKG2D ligands on cancer cells. The starting dose of NKX101 in Part 1/Regimen A is 1 × 10^8 NK cells (2 × 10^6/kg for patients < 50 kg) administered as 3 weekly doses. The starting dose of NKX101 in Part 1/Regimen B is 1.5 × 10^8 NK cells (3 × 10^6/kg for patients < 50 kg) administered as 2 weekly doses. Part 2 will use the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of NKX101 as determined in Part 1.
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 30 days after last dose of NKX101 ]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.
- Proportion of subjects experiencing dose-limiting toxicities of NKX101 [ Time Frame: 28 days from first dose of NKX101 ]DLTs are defined as adverse events attributable to NKX101 treatment that occur during Cycle 1 and meet protocol-specified criteria
- Response rate to NKX101 (for Part 2) [ Time Frame: 28 days from first dose of NKX101 ]Responses will be assessed per modified ELN criteria and will include complete and partial remission with and without varying degrees of hematologic recovery
- Assessment of NKX101 half-life [ Time Frame: 28 days from first dose of NKX101 ]Time required for 50% reduction from maximum amount of circulating NKX101
- NKX101 duration of persistence [ Time Frame: Followed up to 2 years after last dose of NKX101 ]Testing NKX101 in peripheral blood every 3 months after dosing to determine persistence
- Evaluation of host immune response against NKX101 [ Time Frame: Followed up to 2 years after last dose of NKX101 ]Serum samples will be measured for antibodies against NKX101
- Response rate to NKX101 [ Time Frame: Primary assessment: 28 days after first dose of NKX101 followed up to 2 years after last dose of 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])
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04623944
|Contact: David Shook, MD||+1 email@example.com|
|Contact: Cornell Chang||+1 firstname.lastname@example.org|
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|Denver, Colorado, United States, 80218|
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|Chicago, Illinois, United States, 60637|
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|Cleveland, Ohio, United States, 44195|
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|Nashville, Tennessee, United States, 37203|
|Contact: Jeremy Pantin 844-482-4812 email@example.com|
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|MD Anderson Cancer Center, University of Texas||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Carol Bivins 713-794-4460 firstname.lastname@example.org|
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|San Antonio, Texas, United States, 78229|
|Contact: Sherri Shade, RN, CCRC 210-575-4238 email@example.com|
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|Study Director:||David Shook, MD||Nkarta Inc.|