A Trial to Determine The Safety and Efficacy of CC-92480 Alone and When Combined With Dexamethasone in People Who Have Myeloma That is Not Responsive After Treatment or Who Had Myeloma Which Has Returned After a Period of Treatment
- Conditions
- Relapsed and refractory multiple myeloma (RRMM)MedDRA version: 21.1Level: LLTClassification code 10067095Term: Multiple myeloma progressionSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]MedDRA version: 16.1Level: HLTClassification code 10028229Term: Multiple myelomasSystem Organ Class: 100000004851
- Registration Number
- EUCTR2017-001236-19-GB
- Lead Sponsor
- Celgene Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 201
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. Measurable disease is defined as:
a. M-protein quantities = 0.5 g/dL by sPEP or
b. = 200 mg/24 hour urine collection by uPEP or
c. Serum FLC levels > 100 mg/L (milligrams/liter) involved light chain and an abnormal kappa/lambda (?/?) ratio in subjects without measurable or urine M-protein or
d. for subjects with immunoglobulin class A (IgA) myeloma whose disease can only be reliably measured by quantitative immunoglobulin measurement, a serum IgA level = 0.50 g/dL
6. All subjects must have:
a. received at least 3 prior anti-myeloma regimens including at least 2 consecutive cycles of lenalidomide, pomalidomide, a proteasome inhibitor, a glucocorticoid and a CD38 antibody (note: induction with or without bone marrow transplant and with or without maintenance therapy is considered one regimen),
b. documented disease progression on or within 60 days from the last dose of their last myeloma therapy,
i. subjects who had CAR-T therapy as their last myeloma therapy are eligible as long as they have documented disease progression following CAR-T therapy,
c. in addition to criteria above (a and b), subjects enrolled in Part 2, must have disease refractory to an immunomodulatory agent (lenalidomide and/or pomalidomide), a glucocorticoid, a proteasome inhibitor, and a CD38 antibody. Refractory is defined as disease that is nonresponsive on therapy (failure to achieve minimal response or development of progressive disease), or progresses within 60 days of last dose.
7. Subjects must have the following laboratory values:
a. Absolute neutrophil count (ANC) = 1.25 x 10 to the power of 9 /L without growth factor support for = 7 days (= 14 days for pegfilgrastim). ANC of = 1.00 x 10 to the power 9/L is permitted for the dose expansion cohorts (Part 2).
b. Hemoglobin (Hgb) = 8 g/dL.
c. Platelets (plt) = 75 x 10 to the power of 9 /L without transfusion for = 7 days (= 50 x 10 to the power of 9 /L for subjects with > 50% plasma cells in bone marrow).
d. Corrected serum calcium = 13.5 mg/dL (= 3.4 mmol/L).
e. Creatinine clearance (CrCl) based on Cockcroft-Gault formula = 45 mL/min.
f. AST/SGOT and ALT/SGPT = 3.0 x upper limit of normal (ULN).
g. Serum bilirubin = 1.5 x ULN or < 3.0 mg/dL for subjects with documented Gilbert’s syndrome.
h. Uric acid = 7.5 mg/dL (446 µmol/L).
i. PT/INR < 1.5 x ULN and partial thromboplastin time (PTT) < 1.5 x ULN, (for subjects not receiving therapeutic anticoagulation).
8. Females of childbearing potential (FCBP) must:
a. 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.
b. 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 contrace
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-secretory multiple myeloma.
5. Subject has refractory primary multiple myeloma (ie, no history of at least a minor response to a prior treatment regimen).
6. Subject has plasma cell leukemia or active leptomeningeal myelomatosis.
7. Subject has documented, systemic light chain amyloidosis or Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes (POEMS) Syndrome.
8. Subject has immunoglobulin class M (IgM) myeloma.
9. Part 1: Subject has a history of allogeneic bone marrow transplantation. Part 2: Subject has a history of allogeneic bone marrow transplantation within 6 months prior to first dose. Subject should not have ongoing graft-versus-host disease (GVHD) requiring systemic immunosuppression.
10. Subject is undergoing dialysis.
11. Subjects with peripheral neuropathy = Grade 2.
12. Subjects with gastrointestinal disease that may significantly alter the absorption of CC-92480.
13. 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 as defined by repeated demonstration of a QTc interval >480 milliseconds (ms) using Fridericia’s QT correction formula; a history of or current risk factors for Torsades de Pointe (eg. heart failure, hypokalemia, or a family history of Long QT Syndrome); 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.
14. Concurrent administration of strong CYP3A modulators; concurrent administration of proton-pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, pantoprazole) = 2 weeks prior to starting CC-92480 (see Section 8.2).
15. Subject had prior systemic myeloma treatment with an investigational anti-myeloma agent (eg, anti-PD-1, anti-PD-L1) = 5 half-lives prior to starting CC-92480 (not applicable for subjects who had CAR-T as last prior regimen); subject had prior exposure
to approved myeloma therapies (including therapeutic monoclonal antibodies such as anti-CD38 or anti-SLAM-7) = 5 half-lives or within 4 weeks prior to starting CC-92480 whichever is shorter.
16. Subject had major surgery = 2 weeks prior to starting CC-92480. Note: Subjects must have recovered from any clinically significant effects of recent surgery.
17. Subject is a pregnant or nursing female, or intends to become pregnant or donate ova during participation in the study.
18. Subject has known human immunodeficiency virus (HIV) infection.
19. Subject has known active chronic hepatitis B or C virus (HBV/HC
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method