NKX101, Intravenous Allogeneic CAR NK Cells, in Adults With AML or MDS
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04623944 |
|
Recruitment Status :
Recruiting
First Posted : November 10, 2020
Last Update Posted : April 15, 2022
|
Sponsor:
Nkarta Inc.
Information provided by (Responsible Party):
Nkarta Inc.
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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
| 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 |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
|
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.
Other Names:
|
Primary Outcome Measures :
- 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
Secondary Outcome Measures :
- 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])
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
-
General:
- ECOG performance status ≤2
- Haplo-matched related subjects require a suitable haplo-matched related donor, who is able and willing to undergo leukapheresis
-
Disease related:
-
For AML subjects:
- Previously treated relapsed/refractory AML, including subjects with MRD+ disease
- Received at least 1 and at most 2 lines of previous standard anti-leukemia therapy
- For subjects with 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 3 lines of prior therapy
- White blood cell count of ≤25 × 10^9/L
-
For MDS subjects:
- Intermediate-, high-, or very high-risk MDS
- Previously treated relapsed/refractory MDS
- Received at least 1 and at most 2 lines of previous standard anti-MDS therapy
-
- 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)
- 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
Information from the National Library of Medicine
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
Contacts
| Contact: David Shook, MD | +1 415-651-5080 | medmonitor@nkartatx.com | |
| Contact: Cornell Chang | +1 415-651-5060 | clinops@nkartatx.com |
Locations
| United States, Colorado | |
| Colorado Blood Cancer Institute | Recruiting |
| Denver, Colorado, United States, 80218 | |
| Contact: Marcello Rotta 844-482-4812 asksarah@sarahcannon.com | |
| Principal Investigator: Marcello Rotta, MD | |
| United States, Georgia | |
| Winship Cancer Institute, Emory University | Recruiting |
| Atlanta, Georgia, United States, 30322 | |
| Contact: Corey Williams 404-251-2014 corey.williams2@emory.edu | |
| Principal Investigator: William Blum, MD | |
| United States, Illinois | |
| University of Chicago Medical Center | Recruiting |
| Chicago, Illinois, United States, 60637 | |
| Contact: Hongtao Liu, MD, PhD 773-834-0589 hliu2@medicine.bsd.uchicago.edu | |
| Principal Investigator: Hongtao Liu, MD, PhD | |
| United States, Ohio | |
| The Cleveland Clinic - Taussig Cancer Institute | Recruiting |
| Cleveland, Ohio, United States, 44195 | |
| Contact: Betty Hamilton, MD hamiltb2@ccf.org | |
| Principal Investigator: Betty Hamilton, MD | |
| United States, Tennessee | |
| Sarah Cannon at TriStar Bone Marrow Transplant Center | Recruiting |
| Nashville, Tennessee, United States, 37203 | |
| Contact: Jeremy Pantin 844-482-4812 asksarah@sarahcannon.com | |
| Principal Investigator: Jeremy Pantin, MD | |
| United States, Texas | |
| MD Anderson Cancer Center, University of Texas | Recruiting |
| Houston, Texas, United States, 77030 | |
| Contact: Carol Bivins 713-794-4460 cbibins@mdanderson.org | |
| Principal Investigator: Gautam Borthakur, MD | |
| Methodist Healthcare System of San Antonio | Recruiting |
| San Antonio, Texas, United States, 78229 | |
| Contact: Sherri Shade, RN, CCRC 210-575-4238 sherri.shade@mhshealth.com | |
| Principal Investigator: Carlos Bachier, MD | |
Sponsors and Collaborators
Nkarta Inc.
Investigators
| Study Director: | David Shook, MD | Nkarta Inc. |
| Responsible Party: | Nkarta Inc. |
| ClinicalTrials.gov Identifier: | NCT04623944 |
| Other Study ID Numbers: |
NKX101-101 |
| First Posted: | November 10, 2020 Key Record Dates |
| Last Update Posted: | April 15, 2022 |
| Last Verified: | April 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Nkarta Inc.:
|
NKG2D CAR Allogeneic Natural killer ACR NKX101 IL15 |
Interleukin 15 NK cell Cell Therapy Immunotherapy Adoptive cell therapy r/r AML Off-the-shelf |
Additional relevant MeSH terms:
|
Myelodysplastic Syndromes Bone Marrow Diseases Hematologic Diseases Cytarabine Cyclophosphamide Fludarabine Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents |
Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antimetabolites, Antineoplastic Antimetabolites Antiviral Agents Anti-Infective Agents |