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Natural Killer Cell (CYNK-001) Infusions in Adults With AML (CYNK001AML01)

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: NCT04310592
Recruitment Status : Recruiting
First Posted : March 17, 2020
Last Update Posted : June 17, 2020
Sponsor:
Information provided by (Responsible Party):
Celularity Incorporated

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.

Condition or disease Intervention/treatment Phase
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 Biological: CYNK-001 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 22 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Experimental: Cyclophosphamide + Fludarabine + CYNK-001. On Days 0, 7, and 14, CYNK-001 at 3 varying dose levels.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Multi-dose Study of Human Placental Hematopoietic Stem Cell Derived Natural Killer Cells (CYNK-001) in Adults With Newly Diagnosed Primary or Secondary AML in Morphologic Complete Remission With Minimal Residual Disease
Actual Study Start Date : March 12, 2020
Estimated Primary Completion Date : January 3, 2022
Estimated Study Completion Date : January 3, 2022


Arm Intervention/treatment
Experimental: Dose escalation/MTD or MPD determination
Cyclophosphamide + Fludarabine prior to CYNK-001 on Days 0, 7, and 14; CYNK-001 at 3 varying dose levels.
Biological: CYNK-001
CYNK-001 is an allogeneic off the shelf cell therapy enriched for CD56+/CD3- NK cells expanded from human placental CD34+ cells.




Primary Outcome Measures :
  1. Number of Participants who experience a Dose-limiting Toxicity (DLT) [ Time Frame: Day +28 ]
    The number of participants who experience a DLT will be measured.

  2. Determine the Maximum Tolerated Dose (MTD) or Maximum Planned Dose (MPD) of CYNK-001 [ Time Frame: up to 28 days ]
    The maximum dose safely administered for the treatment of patients with AML.

  3. Frequency and Severity of Adverse Events (AEs) [ Time Frame: up to 12 months ]
    Frequency and severity of Adverse Events will be evaluated.


Secondary Outcome Measures :
  1. Number of Participants who experience Minimal Residual Disease (MRD) Response [ Time Frame: up to 12 months ]
    The number of participants who convert from MRD positive to MRD negative.

  2. Time to MRD Response [ Time Frame: up to 12 months ]
    The time it takes to convert from MRD positive to MRD negative.

  3. Duration of MRD Response [ Time Frame: up to 12 months ]
    The measure of how long participants remain MRD negative.

  4. Progression-free Survival (PFS) [ Time Frame: up to 12 months ]
    Date of first CYNK-001 infusion to date of disease progression.

  5. Time to Progression (TTP) [ Time Frame: up to 12 months ]
    Date of first CYNK-001 infusion to date of disease progression.

  6. Duration of Morphologic Complete Remission (CR) [ Time Frame: up to 12 months ]
    Duration from first Morphologic CR observation to time of disease progression.

  7. Overall Survival (OS) [ Time Frame: up to 12 months ]
    Date of first CYNK-001 infusion to date of death.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Treatment Eligibility Screening Subject Inclusion Criteria

Subjects must satisfy the following criteria to be enrolled in the study:

  1. Subject has eligible disease status: Primary or Secondary acute myeloid leukemia (AML) subjects in 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).
  2. Subjects 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.
  3. Subject is minimal residual disease (MRD) positive, as assessed on bone marrow aspirate (BMA) by Multiparameter Flow Cytometry (MFC) at time of Treatment Eligibility assessment.

    a. 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.

  4. Subject is ≥ 18 and ≤ 75 years of age at the time of signing the Study informed consent form (ICF).
  5. Subject understands and voluntarily signs the Study ICF prior to any study-related assessments/procedures are conducted. Subject is willing and able to adhere to the study schedule and other protocol requirements.
  6. Performance status of Eastern Cooperative Oncology Group (ECOG) ≤ 2.
  7. Ability to be off immunosuppressive drugs for at least 3 days prior to the CYNK-001 infusion. Steroids at the equivalent of no more than 7.5 mg prednisone per day are permissible.
  8. Female of childbearing potential (FCBP)* must not be pregnant and agree to not becoming pregnant for at least 28 days following the CYNK-001. FCBP must agree to use an adequate method of contraception during the treatment period.

    • FCBP is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
  9. Male subjects must agree to use a condom during sexual contact for at least 28 days following the last infusion of CYNK-001, even if he has undergone a successful vasectomy.

Treatment Eligibility Screening Subject Exclusion Criteria

The presence of any of the following will exclude the subject from enrollment:

  1. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
  2. Subject has any condition including the presence of laboratory abnormalities which places the subject at unacceptable risk if he or she were to participate in the study.
  3. Subject has any condition that confounds the ability to interpret data from the study.
  4. Subject has bi-phenotypic acute leukemia.
  5. Subject has acute promyelocytic leukemia (APL).
  6. Subject has relapsed/refractory AML.
  7. Subject has inadequate organ function as defined below at time of Treatment Eligibility Period:

    1. Subject has aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase ≥ 2.5 x the upper limit of normal (ULN).
    2. 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.
    3. Subject has a bilirubin level > 2 mg/dL (unless subject has known Gilbert's disease).
  8. Subject 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.
  9. Subject is pregnant or breastfeeding.
  10. Subject 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.
  11. Subject has active autoimmune disease other than controlled connective tissue disorder or those who are not on active therapy.
  12. Subject has had a Bone Marrow transplant as part of their anti-AML treatment prior to first CYNK-001 infusion or plans to have transplant within the 28 day period following first CYNK-001 infusion.
  13. Subject has a history of malignancy other than AML or myelodysplastic syndromes (MDS), unless the subject has been free of disease for greater than 3 years prior to CYNK 001 infusion. Exceptions will include the following malignancies:

    1. Basal cell carcinoma of the skin
    2. Squamous cell carcinoma of the skin
    3. Carcinoma in situ of the cervix
    4. Carcinoma in situ of the breast
    5. Incidental biological finding of prostate cancer (TNM stage of T1a or T1b)
  14. Subject has a history of severe asthma and is presently on chronic medications or has a history of other symptomatic pulmonary disease.
  15. Subject has uncontrolled graft versus host disease (GVHD).
  16. Subject has an untreated chronic infection or has received treatment of any infection with systemic antibiotics within 2 weeks prior to first CYNK-001 infusion. Prophylactic antibiotic, antiviral, and antifungal medication are permissible.
  17. Subject has any other organ dysfunction (CTCAE Version 5.0 Grade 3 or greater) that will interfere with the administration of the therapy according to this protocol.
  18. Subject has a resting left ventricular ejection fraction (LVEF) of < 45% obtained by echocardiography or multi-gated acquisition scan (MUGA).
  19. Subject was treated with an investigational product within 28 days of first CYNK-001 infusion. Subject must no longer be a participant in the previous interventional study at the time of CYNK-001 infusion. (Subjects who are under survival follow-up or observation associated with a study are permitted, and if treatment information is collected for this period, "Investigational Study" must be used to capture the study treatment.).

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): NCT04310592


Contacts
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Contact: Erica Rave, MS 9088454338 erica.rave@celularity.com
Contact: Solveig Ericson, MD, PhD 9088454182 solveig.ericson@celularity.com

Locations
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United States, Colorado
Colorado Blood Cancer Institute Recruiting
Denver, Colorado, United States, 80218
Principal Investigator: Michael Maris, MD         
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Hongtao Liu, MD, PhD         
Principal Investigator: Hongtao Liu, MD, PhD         
United States, Tennessee
Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Contact: MD         
Principal Investigator: William Donnellan, MD         
Sponsors and Collaborators
Celularity Incorporated
Investigators
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Study Director: Solveig Ericson, MD, PhD Celularity, Inc.
Publications:
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Responsible Party: Celularity Incorporated
ClinicalTrials.gov Identifier: NCT04310592    
Other Study ID Numbers: CYNK-001-AML-001
First Posted: March 17, 2020    Key Record Dates
Last Update Posted: June 17, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Celularity Incorporated:
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
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Hematologic Neoplasms
Neoplasms by Histologic Type
Hematologic Diseases
Neoplasms
Neoplasms by Site