Natural Killer Cell (CYNK-001) Infusions in Adults with AML

NCT04310592 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: CYNK-001-AML-001
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 10

Brief Summary

This study will find the maximum tolerated dose or the maximum planned dose of CYNK-001 which contains natural killer (NK) cells derived from human placental CD34+ cells and culture-expanded. CYNK-001 cells will be given after lymphodepleting chemotherapy. The safety of this treatment will be evaluated, and researchers want to learn if NK cells will help in treating acute myeloid leukemia.

Conditions

Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neoplasms by Histologic Type; Neoplasms; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Alkylating Agents; Antimetabolites, Antineoplastic; Antiviral Agents; Analgesics, Non-narcotic; Anti-infective Agents; Analgesics; Peripheral Nervous System Agents; Hematologic Diseases; Hematologic Neoplasms; Leukemia in Remission; Relapsed Adult AML; Refractory AML

Keywords

CYNK-001; Acute Myeloid Leukemia; Acute Myelogenous Leukemia; allogeneic; allogeneic stem cell transplant; AML; cell therapy; cyclophosphamide; fludarabine; minimal residual disease; MRD; newly diagnosed AML; newly diagnosed acute myeloid leukemia; NK cells; natural killer cells; fludarabine phosphate; antineoplastic agents, alkylating; molecular mechanisms of pharmacological action; relapsed AML; refractory AML

Outcome Measures

Primary Outcomes (5)

• Number of Participants who experience a Dose-limiting Toxicity (DLT) in MRD positive AML patients

  The number of participants who experience a DLT will be measured.

  Day +28

• Number of Participants who experience a Dose-limiting Toxicity (DLT) in Relapsed/Refractory AML patients

  The number of participants who experience a DLT will be measured.

  Day +28

• Determine the Maximum Tolerated Dose (MTD) or Maximum Planned Dose (MPD) of CYNK-001 in MRD positive AML patients

  The maximum dose safely administered for the treatment of patients with AML.

  up to 28 days

• Determine the Maximum Tolerated Dose (MTD) or Maximum Planned Dose (MPD) of CYNK-001 in Relapsed/Refractory AML patients

  The maximum dose safely administered for the treatment of patients with AML.

  up to 28 days

• Frequency and Severity of Adverse Events (AEs)

  Frequency and severity of Adverse Events will be evaluated.

  up to 12 months

Secondary Outcomes (9)

• Number Participants who experience Minimal Residual Disease (MRD) Response

  up to 12 months

• Time to MRD Response

  up to 12 months

• Duration of MRD Response

  up to 12 months

• Progression-free Survival (PFS)

  up to 12 months

• Time to Progression (TTP)

  up to 12 months

Study Arms (2)

Dose escalation/MTD or MPD determination in MRD positive AML patients

EXPERIMENTAL

Cyclophosphamide + Fludarabine prior to CYNK-001 on Days 0, 7, and 14; CYNK-001 at 3 varying dose levels.

Biological: CYNK-001

Dose escalation/MTD or MPD determination in Relapsed/Refractory AML patients

EXPERIMENTAL

Cyclophosphamide + Fludarabine prior to CYNK-001 on Days 0, 7, and 14; CYNK-001 at 3 varying dose levels.

Biological: CYNK-001

Interventions

CYNK-001 BIOLOGICAL

CYNK-001 is an allogeneic off the shelf cell therapy enriched for CD56+/CD3- NK cells expanded from human placental CD34+ cells.

Dose escalation/MTD or MPD determination in MRD positive AML patients; Dose escalation/MTD or MPD determination in Relapsed/Refractory AML patients

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must satisfy the following criteria to be enrolled in the study:
• Patient has eligible disease status:
• Primary or Secondary acute myeloid leukemia (AML) Patients in first of second Morphological Complete Remission (CR), Morphological Complete Remission with incomplete hematologic recovery (CRi), or Morphologic Leukemia-free State (MLFS) as defined by the European LeukemiaNet (ELN) recommendations for AML Response Criteria (Dohner, 2017).
• R/R diagnosis based on confirmed diagnosis with local pathology report following any reinduction/ salvage therapy ELN guidelines.
• Relapsed AML are defined as having relapsed after achieving ≥ 1 CR, including relapse after allogeneic stem cell transplantation (≥ 2 months after transplant).
• Refractory AML, defined as not achieving CR, CRi, or MLFS after 2 or more cycles of induction therapy (primary refractory) or not achieving CR after treatment for relapsed AML.
• Secondary AML (MDS transformation): Secondary AML patients are eligible to participate if they have received a minimum of one prior line of treatment for AML.
• Treatment-related AML: Treatment-related AML patients are eligible to participate if they have received a minimum of one prior line of treatment for AML.
• Patient with prior central nervous system involvement by malignancy are eligible provided that it has been treated and cerebral spinal fluid is clear for at least 2 weeks prior to start of Lymphodepletion Regimen.
• (MRD positive population only): Patient is minimal residual disease (MRD) positive, as assessed on bone marrow aspirate (BMA) by Multiparameter Flow Cytometry (MFC) at time of Treatment Eligibility assessment.
• For the purposes of this study, MRD positivity is defined as greater than or equal to 0.1% blasts detected by MFC on BMA by the Sponsor-selected Central MRD analysis laboratory, where assay sensitivity allows for a Lower Limit of Detection (LOD) of 1 x 10-4 (0.01%) or lower.
• Patient is ≥ 18 and ≤ 80 years of age at the time of signing the Study informed consent form (ICF).
• Patient understands and voluntarily signs the Study ICF prior to any study-related assessments/procedures are conducted.
• Patient is willing and able to adhere to the study schedule and other protocol requirements.
• Performance status of Eastern Cooperative Oncology Group (ECOG) ≤ 2.

You may not qualify if:

• The presence of any of the following will exclude the Patient from enrollment:
• Patient has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the Patient from participating in the study.
• Patient has any condition including the presence of laboratory abnormalities which places the Patient at unacceptable risk if he or she were to participate in the study.
• Patient has any condition that confounds the ability to interpret data from the study.
• Patient has bi-phenotypic acute leukemia.
• Patient has acute promyelocytic leukemia (APL).
• Patient has inadequate organ function as defined below at time of Treatment Eligibility Period:
• Patient has aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase ≥ 2.5 x the upper limit of normal (ULN).
• Estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m2 as calculated using the Modification of Diet in Renal Disease Study equation (Levey, 2006) or history of an abnormal eGFR \< 60 and a decline of \> 15 mL/min/1.73 m2 below normal in the past year.
• Patient has a bilirubin level \> 2 mg/dL (unless Patient has known Gilbert's disease).
• Patient has had prior treatment with biologic antineoplastic agents less than 7 days before first CYNK-001 infusion and at least 5 half-lives. (Exception will be granted for monoclonal antibodies that are known to have long half-lives, in which case a minimum of 2 weeks from last dose will be required). For agents that have known AEs occurring beyond these specified days after administration, this period must be extended beyond the time during which acute AEs are known to occur. Treating physicians are encouraged to discuss cases with the Medical Monitor.
• Patient is pregnant or breastfeeding.
• Patient has new or progressive pulmonary infiltrates or pleural effusion large enough to be detected by chest x-ray or CT scan within 2 weeks of first CYNK-001 infusion.
• Patient has active autoimmune disease other than controlled connective tissue disorder or those who are not on active therapy.
• Patient has had a Bone Marrow transplant \< 60 days prior to screening or plans to have a transplant within the 28 day period following the first CYNK-001 infusion.

Sponsors & Collaborators

• Celularity Incorporated: lead

Study Sites (10)

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14203, United States

Location

Columbia University and New York Presbyterian Hospital

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Westchester Medical Center

Valhalla, New York, 10595, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Swedish Health Services

Seattle, Washington, 98122, United States

Location

Related Publications (2)

• Dohner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Buchner T, Dombret H, Ebert BL, Fenaux P, Larson RA, Levine RL, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz M, Sierra J, Tallman MS, Tien HF, Wei AH, Lowenberg B, Bloomfield CD. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017 Jan 26;129(4):424-447. doi: 10.1182/blood-2016-08-733196. Epub 2016 Nov 28.

  PMID: 27895058 BACKGROUND

• Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S, Kusek JW, Van Lente F; Chronic Kidney Disease Epidemiology Collaboration. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006 Aug 15;145(4):247-54. doi: 10.7326/0003-4819-145-4-200608150-00004.

  PMID: 16908915 BACKGROUND

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hematologic Neoplasms; Neoplasm, Residual

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Neoplasms by Site; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Sharmila Koppisetti, M.D

  Celularity, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Experimental: Minimal Residual Disease (MRD) positive AML patients; Cyclophosphamide + Fludarabine + CYNK-001. On Days 0, 7, and 14, (and 21 in certain arms) CYNK-001 at 3 varying dose levels. Experimental: Relapsed/Refractory AML patients; Cyclophosphamide + Fludarabine + CYNK-001. On Days 0, 7, and 14, (and 21 at certain dose levels) CYNK-001 at 3 varying dose levels.

Study Record Dates

• First Submitted: March 12, 2020
• First Posted: March 17, 2020
• Study Start: March 12, 2020
• Primary Completion: January 20, 2023
• Study Completion: April 28, 2023
• Last Updated: December 12, 2024

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)