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Natural Killer Cell (CYNK-001) Infusions in Adults With Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT04309084
Recruitment Status : Recruiting
First Posted : March 16, 2020
Last Update Posted : April 19, 2021
Sponsor:
Information provided by (Responsible Party):
Celularity Incorporated

Tracking Information
First Submitted Date  ICMJE March 12, 2020
First Posted Date  ICMJE March 16, 2020
Last Update Posted Date April 19, 2021
Actual Study Start Date  ICMJE May 12, 2020
Estimated Primary Completion Date November 12, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 13, 2021)
  • Dose-Limiting Toxicity (DLT) [ Time Frame: Up to 28 days ]
    Safety Assessment of Dose-Limiting Toxicity (DLT)
  • Maximum Tolerated Dose (MTD) or Maximum Planned Dose (MPD) [ Time Frame: Up to 28 days ]
    Safety Assessment of MTD OR MPD
  • Adverse Events (AE) [ Time Frame: Up to 12 months ]
    Safety Assessment of AE's
  • Rate of Minimal Residual Disease (MRD) Negativity [ Time Frame: Day 90-100 ]
    Efficacy Assessment of MRD
Original Primary Outcome Measures  ICMJE
 (submitted: March 13, 2020)
  • Dose-Limiting Toxicity (DLT) [ Time Frame: Up to 28 days ]
    Phase I
  • Maximum Tolerated Dose (MTD) or Maximum Planned Dose (MPD) [ Time Frame: Up to 28 days ]
    Phase I
  • Adverse Events (AE) [ Time Frame: Up to 12 months ]
  • Rate of Minimal Residual Disease (MRD) Negativity [ Time Frame: Day 90-100 ]
    Phase II
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 13, 2021)
  • Minimal Residual Disease (MRD) Response [ Time Frame: Day 90-100 ]
    Efficacy Assessment of MRD
  • Time to MRD Response [ Time Frame: up to 12 months ]
    Efficacy Assessment of MRD
  • International Myeloma Working Group (IMWG) response [ Time Frame: up to 12 months ]
    Efficacy Assessment of response
  • duration of clinical response [ Time Frame: up to 12 months ]
    Efficacy Assessment of response
  • Progression-free survival [ Time Frame: up to 12 months ]
    Efficacy Assessment of response
  • time to progression [ Time Frame: up to 12 months ]
    Efficacy Assessment of response
  • overall survival [ Time Frame: up to 12 months ]
    Efficacy Assessment of response
  • Quality of life questionnaire [ Time Frame: up to 12 months ]
    Efficacy Assessment of response
Original Secondary Outcome Measures  ICMJE
 (submitted: March 13, 2020)
  • Minimal Residual Disease (MRD) Response [ Time Frame: Day 90-100 ]
    Phase I/II
  • Time to MRD Response [ Time Frame: up to 36 months ]
    Duration of MRD Response Phase I/II
  • International Myeloma Working Group (IMWG) response [ Time Frame: up to 36 months ]
    Phase I/II
  • duration of clinical response [ Time Frame: up to 36 months ]
    Phase I/II
  • Progression-free survival [ Time Frame: up to 36 months ]
    Phase I/II
  • time to progression [ Time Frame: up to 36 months ]
    Phase I/II
  • overall survival [ Time Frame: up to 36 months ]
    Phase I/II
  • Quality of life questionnaire [ Time Frame: up to 36 months ]
    patient reported outcome (Phase II)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Natural Killer Cell (CYNK-001) Infusions in Adults With Multiple Myeloma
Official Title  ICMJE A Phase I Study of Human Placental Hematopoietic Stem Cell Derived Natural Killer Cells (CYNK 001) in Multiple Myeloma Patients Following Autologous Stem Cell Transplant in the Front-line Setting.
Brief Summary This study will find the maximum tolerated dose (MTD) of CYNK-001 which contain NK cells derived from human placental CD34+ cells and culture-expanded. CYNK-001 cells will be given post Autologous Stem Cell Transplant (ASCT). The safety of this treatment will be evaluated, and researchers will want to learn if NK cells will help in treating Multiple Myeloma.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description:
The study will utilize a 3+3 open label design, and will enroll up to three dosing cohorts of CYNK-001 given on Day 2 or Days 2, 7, 14 post ASCT. Once MTD has been determined, the Expansion cohort will commence.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Multiple Myeloma
  • Neoplasm, Plasma Cell
  • Neoplasms by Histologic Type
  • Neoplasms
  • Hemostatic Disorder
  • Vascular Diseases
  • Cardiovascular Diseases
  • Paraproteinemias
  • Blood Protein Disorders
  • Hematologic Diseases
  • Hemorrhagic Disorders
  • Lymphoproliferative Disorders
  • Immunoproliferative Disorders
  • Immune System Diseases
  • Antineoplastic Agents
  • Analgesics, Non-Narcotic
  • Analgesics
  • Sensory System Agents
  • Peripheral Nervous System Agents
  • Physiological Effects of Drugs
Intervention  ICMJE 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.
Study Arms  ICMJE Experimental: Phase I
Up to three dosing cohorts of CYNK-001 given on Day 2 or Days 2, 7, 14 post ASCT. Once MTD has been determined, the Expansion cohort will commence.
Intervention: Biological: CYNK-001
Publications * 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. Erratum in: Ann Intern Med. 2008 Oct 7;149(7):519. Erratum in: Ann Intern Med. 2021 Apr;174(4):584.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 13, 2021)
29
Original Estimated Enrollment  ICMJE
 (submitted: March 13, 2020)
108
Estimated Study Completion Date  ICMJE November 12, 2022
Estimated Primary Completion Date November 12, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Subject Inclusion Criteria

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

  1. Subject has eligible disease status:

    Newly diagnosed multiple myeloma undergoing or completed induction therapy prior to undergoing first ASCT and presenting MRD positive by NGS after completion of induction therapy.

  2. Subject is > 18 and ≤ 75 years of age at the time of signing the informed consent form (ICF).
  3. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
  4. Subject is willing and able to adhere to the study schedule and other protocol requirements.
  5. Performance status of Eastern Cooperative Oncology Group (ECOG) < 2
  6. Ability to be off immunosuppressive drugs for at least 3 days prior to the CYNK-001 cell infusion. Steroids at the equivalent of no more than 5 mg prednisone per day are permissible.
  7. Subjects must have autologous peripheral blood stem cell graft available in storage for additional transplant in the event of engraftment failure.
  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 (ie, 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 CYNK-001, even if he has undergone a successful vasectomy.

Subject Exclusion Criteria

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

  1. Subject has plasma cell leukemia.
  2. Subject has non-secretory myeloma.
  3. Subject has previously undergone allogeneic stem cell transplant.
  4. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
  5. 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.
  6. Subject has any condition that confounds the ability to interpret data from the study.
  7. Subject has a known sensitivity or allergy to lenalidomide which will limit the subject from receiving the mandatory lenalidomide maintenance as part of the study plan.
  8. Subject has aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase ≥ 2.5 x the upper limit of normal (ULN) within 7 days prior to melphalan administration. Transient abnormalities should be discussed with the medical monitor.
  9. This eligibility criterion removed with Amendment 1
  10. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 at screening calculated using the Modification of Diet in Renal Disease Study equation. (Levey, 2006)
  11. Subject has a bilirubin level > 2 mg/dL (unless subject has known Gilbert's disease) at screening.
  12. Subject has had prior treatment with biologic antineoplastic agents less than 7 days before CYNK-001 infusion and at least 5 half-lives since (excludes melphalan). (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.
  13. Subject is pregnant or breastfeeding.
  14. Subject has new or progressive pulmonary infiltrates or pleural effusion large enough to be detected by chest x-ray or computerized tomography (CT) scan within 2 weeks of CYNK-001 infusion.
  15. Subject has active autoimmune disease other than controlled connective tissue disorder or those who are not on active therapy.
  16. Subject who is human immunodeficiency virus (HIV) positive is excluded due to increased risk of lethal infections when treated with myeloablative chemotherapy.
  17. Subject has history of malignancy, other than MM, unless the subject has been free of disease for > 3 years from the date of signing the ICF. Exceptions include the following noninvasive malignancies:

    1. Basal cell carcinoma of the skin
    2. Squamous cell carcinoma of the skin CYNK-001
    3. Carcinoma in situ of the cervix
    4. Carcinoma in situ of the breast
    5. Incidental histological finding of prostate cancer (TNM stage of T1a or T1b)
  18. Subject has a history of severe asthma and is presently on chronic medications or has a history of other symptomatic pulmonary disease.
  19. Untreated chronic infection or treatment of any infection with systemic antibiotics within 2 weeks prior to melphalan.
  20. Subject has any other organ dysfunction (Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 Grade 3 or greater) that will interfere with the administration of the therapy according to this protocol.
  21. Subject has a resting left ventricular ejection fraction (LVEF) of < 35% obtained by echocardiography or multigated acquisition scan (MUGA).
  22. Subject was treated with an investigational product no less than 28 days before CYNK-001 infusion. Subject must no longer be a participant in the previous interventional study at the time of the 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 for capturing the study treatment.)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04309084
Other Study ID Numbers  ICMJE CYNK-001-MM-002
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Celularity Incorporated
Study Sponsor  ICMJE Celularity Incorporated
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Celularity Incorporated
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP