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

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: NCT04309084
Recruitment Status : Recruiting
First Posted : March 16, 2020
Last Update Posted : June 5, 2020
Sponsor:
Information provided by (Responsible Party):
Celularity Incorporated

Brief Summary:
This study will find the maximum tolerated dose 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. The safety of this treatment will be evaluated, and researchers want to learn if NK cells will help in treating Multiple Myeloma.

Condition or disease Intervention/treatment Phase
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 Biological: CYNK-001 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 108 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Phase I will utilize a 3+3 open label design, and will enroll up to two dosing cohorts of CYNK-001 given on Day 2 or Days 2, 7, 14 post ASCT. Phase II will utilize the phase I determined dose, and will be double blinded/ randomized to CYNK-001 or placebo.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase I/II 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.
Actual Study Start Date : May 12, 2020
Estimated Primary Completion Date : March 12, 2023
Estimated Study Completion Date : March 12, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Phase I
Up to two dosing cohorts of CYNK-001 given on Day 2 or Days 2, 7, 14 post ASCT.
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.

Placebo Comparator: Phase II
CYNK-001 or Placebo (using Phase I determined dose)
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. Dose-Limiting Toxicity (DLT) [ Time Frame: Up to 28 days ]
    Phase I

  2. Maximum Tolerated Dose (MTD) or Maximum Planned Dose (MPD) [ Time Frame: Up to 28 days ]
    Phase I

  3. Adverse Events (AE) [ Time Frame: Up to 12 months ]
  4. Rate of Minimal Residual Disease (MRD) Negativity [ Time Frame: Day 90-100 ]
    Phase II


Secondary Outcome Measures :
  1. Minimal Residual Disease (MRD) Response [ Time Frame: Day 90-100 ]
    Phase I/II

  2. Time to MRD Response [ Time Frame: up to 36 months ]
    Duration of MRD Response Phase I/II

  3. International Myeloma Working Group (IMWG) response [ Time Frame: up to 36 months ]
    Phase I/II

  4. duration of clinical response [ Time Frame: up to 36 months ]
    Phase I/II

  5. Progression-free survival [ Time Frame: up to 36 months ]
    Phase I/II

  6. time to progression [ Time Frame: up to 36 months ]
    Phase I/II

  7. overall survival [ Time Frame: up to 36 months ]
    Phase I/II

  8. Quality of life questionnaire [ Time Frame: up to 36 months ]
    patient reported outcome (Phase II)



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.


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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

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. Subject may not have transfusion of blood products (ie, packed red blood cells, whole blood etc) within 24 hours of CYNK-001 infusions.
  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.)

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): NCT04309084


Locations
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United States, Colorado
Colorado Blood Cancer Institute Recruiting
Denver, Colorado, United States, 80218
Contact: James Vick    720-754-4800    James.Vick@SarahCannon.com   
Principal Investigator: Tara Gregory, MD         
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Shantoria Brown    404-778-6547    shantoria.mayes@emory.edu   
Principal Investigator: Craig Hofmeister, MD         
United States, Indiana
Franciscan Health Recruiting
Indianapolis, Indiana, United States, 46237
Contact: Melanie Coleman    317-528-7298    melanie.coleman@franciscanalliance.org   
Principal Investigator: Luke P Akard, MD         
United States, Missouri
Washington University Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Justin King    314-747-6775    justinking@wustl.edu   
Principal Investigator: Ravi Vij, MD         
United States, Tennessee
Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Contact: Jennifer Ritchie    615-524-4282    Jennifer.Ritchie2@SarahCannon.com   
Principal Investigator: Jesus Berdeja, MD         
Sponsors and Collaborators
Celularity Incorporated
Publications:
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Responsible Party: Celularity Incorporated
ClinicalTrials.gov Identifier: NCT04309084    
Other Study ID Numbers: CYNK-001-MM-002
First Posted: March 16, 2020    Key Record Dates
Last Update Posted: June 5, 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
Autologous stem cell transplant
Cell therapy
NK cells
Natural killer cells
Multiple Myeloma
Plasma Cell Myeloma
Plasma Cell Neoplasm
Newly Diagnosed Multiple Myeloma
Minimal Residual Disease
MRD
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Vascular Diseases
Hemostatic Disorders
Lymphoproliferative Disorders
Hematologic Diseases
Hemorrhagic Disorders
Blood Coagulation Disorders
Paraproteinemias
Blood Protein Disorders
Immunoproliferative Disorders
Disease
Neoplasms
Cardiovascular Diseases
Immune System Diseases
Pathologic Processes
Lymphatic Diseases