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A Safety, PK and Efficacy Study of CC-92480 in Combination With Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT03374085
Recruitment Status : Recruiting
First Posted : December 15, 2017
Last Update Posted : August 24, 2018
Sponsor:
Information provided by (Responsible Party):
Celgene

Brief Summary:

This is an open-label, multi-center, international, Phase 1 study to assess the safety, PK/PD and preliminary efficacy of CC-92480 in combination with dexamethasone in subjects with RRMM.

All eligible subjects must be refractory to their last line of therapy and have failed, be intolerant to or are not otherwise candidates for available therapies demonstrated to confer clinical benefit to subjects with relapsed and refractory multiple myeloma including (at a minimum), thalidomide, lenalidomide or pomalidomide and a proteasome inhibitor.


Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: CC-92480 Drug: Dexamethasone Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Multicenter, Open-label Study to Assess the Safety, Pharmacokinetics and Preliminary Efficacy of CC-92480 in Combination With Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma
Actual Study Start Date : February 6, 2018
Estimated Primary Completion Date : January 1, 2020
Estimated Study Completion Date : March 1, 2020


Arm Intervention/treatment
Experimental: Administration of CC-92480 and Dexamethasone
Escalating doses of CC-92480 in combination with a fixed dose of dexamethasone administered according to two different dosing schedules
Drug: CC-92480
CC-92480

Drug: Dexamethasone
Dexamethasone




Primary Outcome Measures :
  1. Adverse Events (AEs) [ Time Frame: From enrollment until at least 28 days after completion of study treatment ]
    Number of participants with AEs (Type, frequency, seriousness, severity and relationship of AEs to CC-92480 and dexamethasone; changes from baseline in clinically-relevant physical findings, vital signs, selected laboratory analytes, ECGs).

  2. Pharmacokinetics- AUC [ Time Frame: Up to approximately 28 days ]
    Area under the plasma concentration-time curve

  3. Pharmacokinetics- Cmax [ Time Frame: Up to approximately 28 days ]
    Maximal plasma concentration

  4. Pharmacokinetics- Tmax [ Time Frame: Up to approximately 28 days ]
    Time to Cmax

  5. Pharmacokinetics- t1/2 [ Time Frame: Up to approximately 28 days ]
    Terminal-phase elimination half-life

  6. Pharmacokinetics- CL/F [ Time Frame: Up to approximately 28 days ]
    Apparent total clearance of the drug from plasma after oral administration

  7. Pharmacokinetics- Vz/F [ Time Frame: Up to approximately 28 days ]
    Apparent volume of distribution during terminal phase after non-intravenous administration

  8. Maximum tolerated dose (MTD) [ Time Frame: Up to approximately 28 days ]
    The highest dose of CC-92480 in combination with dexamethasone associated acceptable safety and tolerability.


Secondary Outcome Measures :
  1. Overall response rate (ORR) [ Time Frame: Up to approximately 3 years ]
    Best response ≥ partial response (PR), according to the IMWG Uniform Response Criteria

  2. Time to response (TTR) [ Time Frame: Up to approximately 3 years ]
    Time from 1st dose of CC-92480 to the first documentation of response ≥ PR.

  3. Duration of response (DOR) [ Time Frame: Up to approximately 3 years ]
    Time from the first documentation of response (≥ PR) to the first documentation of PD or death.

  4. Progression free survival [ Time Frame: Up to approximately 3 years ]
    Time from 1st dose of CC-92480 to the first occurrence of disease progression or death from any cause.



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

Inclusion Criteria:

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

  1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).
  2. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
  3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
  4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
  5. Subjects must have a documented diagnosis of MM and measurable disease at enrollment.
  6. Subjects must have the following laboratory values:

    • Absolute neutrophil count (ANC) ≥ 1.25 x 109/L without growth factor support for ≥ 7 days (≥ 14 days for pegfilgrastim).
    • Hemoglobin (Hgb) ≥ 8 g/dL.
    • Platelets (plt) ≥ 75 x 109/L without transfusion for ≥ 7 days (≥ 50 x 109/L for subjects with > 50% plasma cells in bone marrow).
    • Corrected serum calcium ≤ 13.5 mg/dL (≤ 3.4 mmol/L).
    • 24-hr creatinine clearance (CrCl) ≥ 45 mL/min.
    • AST/SGOT and ALT/SGPT ≤ 3.0 x upper limit of normal (ULN).
    • Serum bilirubin ≤ 1.5 x ULN.
    • Uric acid ≤ 7.5 mg/dL (446 μmol/L).
    • PT/INR < 1.5 x ULN and partial thromboplastin time (PTT) < 1.5 x ULN, (for subjects not receiving therapeutic anticoagulation).
  7. Females of childbearing potential (FCBP) must:

    1. Have two negative pregnancy tests as verified by the Investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after discontinuation of CC-92480. This applies even if the subject practices true abstinence* from heterosexual contact.
    2. Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with, two reliable forms of contraception without interruption, 28 days prior to starting CC-92480, during the study therapy (including during dose interruptions), and for 28 days after discontinuation of study therapy.
  8. Male subjects must:

    Practice true abstinence (which must be reviewed on a monthly basis) or agree to use of a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study (even during dose interruptions) and for at least 3 months following CC-92480 discontinuation, even if he has undergone a successful vasectomy.

  9. Males must agree to refrain from donating sperm while on CC-92480 and females must agree to refrain from donating ova while on CC-92480 for 90 days after its discontinuation.

Exclusion Criteria:

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

  1. Subject has a 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/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 non- or oligosecretory multiple myeloma.
  5. Subject has plasma cell leukemia or active leptomeningeal myelomatosis.
  6. Subject has documented, systemic light chain amyloidosis or Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes (POEMS) Syndrome.
  7. Subject has immunoglobulin class M (IgM) myeloma.
  8. Subject has a history of allogeneic bone marrow transplantation.
  9. Subject is undergoing dialysis.
  10. Subjects with peripheral neuropathy ≥ Grade 2.
  11. Subjects with gastrointestinal disease that may significantly alter the absorption of CC-92480.
  12. Subject has impaired cardiac function or clinically significant cardiac disease, including any of the following:

    • LVEF < 45% as determined by ECHO or MUGA scan at Screening.
    • Complete left bundle branch, bifascicular block or other clinically significant abnormal electrocardiographic (ECG) finding at Screening.
    • A prolongation of QT interval on Screening ECG; a history of or current risk factors for Torsades de Pointe; and concurrent administration of medications that prolong the QT/QTc interval.
    • Congestive heart failure (New York Heart Association Class III or IV).
    • Myocardial infarction ≤6 months prior to starting CC-92480.
    • Unstable or poorly controlled angina pectoris, including the Prinzmetal variant of angina pectoris.
  13. Concurrent administration of strong CYP3A modulators.
  14. Subject had prior systemic myeloma treatment within protocol defined period.
  15. Subject had major surgery ≤ 2 weeks prior to starting CC-92480.
  16. Subject is a pregnant or nursing female or intends to become pregnant during participation in the study.
  17. Subject has known human immunodeficiency virus (HIV) infection.
  18. Subject has known active chronic hepatitis B or C virus (HBV/HCV) infection.
  19. Subject has a history of concurrent second cancer requiring ongoing systemic treatment.
  20. Subjects has a history of prior malignancy other than MM, unless the subject has been free of disease for ≥3 years except for noninvasive malignancies treated with curative intent.
  21. Subject has known or suspected hypersensitivity to the excipients contained in the formulation of CC-92480 or dexamethasone.
  22. Subject has undergone either of the following within 14 days of initiating CC-92480:

    • Plasmapheresis.
    • Radiation therapy other than local therapy for symptomatic relief of MM associated bone lesions.
  23. Subject has received immunosuppressive medication within 14 days prior to the first dose of CC-92480.

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): NCT03374085


Contacts
Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com

Locations
United States, California
City of Hope Cancer Center Recruiting
Duarte, California, United States, 91010-300
United States, Colorado
Colorado Blood Cancer Institute Not yet recruiting
Denver, Colorado, United States, 80218
United States, Georgia
Emory Clinic Recruiting
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
United States, Tennessee
Sarah Cannon Cancer Center Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
MD Anderson Cancer Center The University of Texas Recruiting
Houston, Texas, United States, 77030
Canada, Alberta
Tom Baker Cancer Center Recruiting
Calgary, Alberta, Canada, T2N 4N2
Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2M9
Denmark
Rigshospitalet University Hospital Recruiting
Copenhagen, Denmark, 2100
Finland
Helsinki University Hospital Recruiting
Helsinki, Finland, 00029
Spain
Hospital Universitari Germans Trias i Pujol Can Ruti Recruiting
Badalona (Barcelona), Spain, 08916
Hospital 12 de Octobre Recruiting
Madrid, Spain, 28041
Clínica Universidad de Navarra Recruiting
Pamplona, Spain, 31008
Hospital Universitario de Salamanca Recruiting
Salamanca, Spain, 37007
United Kingdom
University College London Hospitals Cancer Clinical Trials Unitist FloorCentral wing Recruiting
London, United Kingdom, NW1 2PG
Oxford University Hospitals NHS Trust- Churchill Hospital-Oxford Centre for Respiratory Medicine Recruiting
Oxford, United Kingdom, 0X3 7LE
The Royal Marsden NHS Foundation Trust Recruiting
Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
Celgene
Investigators
Study Director: Michael Pourdehnad, MD Celgene

Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT03374085     History of Changes
Other Study ID Numbers: CC-92480-MM-001
U1111-1205-3650 ( Registry Identifier: WHO )
2017-001236-19 ( EudraCT Number )
First Posted: December 15, 2017    Key Record Dates
Last Update Posted: August 24, 2018
Last Verified: August 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Celgene:
Multiple Myeloma
Safety
Efficacy
CC-92480
Relapsed
Refractory

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors