IRB Study Number 22-1332
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objective
To compare the progression-free survival (PFS) of CC-92480, bortezomib and dexamethasone (480Vd) to that of pomalidomide, bortezomib and dexamethasone (PVd) in subjects with relapsed or refractory multiple myeloma (RRMM)
Secondary Objective(s)
In Stage 1, to determine the dose of CC-92480 in combination with bortezomib and dexamethasone to continue in Stage 2 of the study
In Stage 1, to determine the plasma concentrations of CC-92480 in combination with bortezomib and dexamethasone
To compare overall survival (OS) between 480Vd and PVd in subjects with RRMM
To evaluate additional efficacy parameters in subjects with RRMM treated with 480Vd compared to PVd
To evaluate minimal residual disease (MRD) negativity rate in subjects treated with 480Vd compared to those treated with PVd
To evaluate safety of 480Vd compared to PVd in subjects with RRMM
In subjects randomized to Stage 2, to evaluate cancer-related symptoms and health-related quality of life (HRQoL) using the European Organization for Research and Treatment of Cancer - Quality of Life C30 questionnaire (EORTC QLQ-C30) and the European Quality of Life Multiple Myeloma Module (EORTC QLQ-MY20) in subjects treated with 480Vd compared to PVd.
Inclusion Criteria
Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).
Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
Subject has documented diagnosis of MM and measurable disease, defined as any of the following:
a. M-protein ≥ 0.5 g/dL by serum protein electrophoresis (sPEP) or
b. M-protein ≥ 200 mg/24-hour urine collection by urine protein electrophoresis (uPEP) or,
c. For subjects without measurable disease in sPEP or uPEP: serum free light chain (sFLC) levels > 100 mg/L (10 mg/dL) involved light chain and an abnormal kappa/lambda FLC ratio.
Subject has received 1 to 3 prior lines of antimyeloma therapy. (Note: One line can contain several phases [eg, induction, (with or without) hematopoietic stem cell transplant, (with or without) consolidation, and/or (with or without) maintenance therapy) See APPENDIX J.
Subject must have received prior treatment with a lenalidomide-containing regimen.
Subject achieved minimal response [MR] or better to at least 1 prior antimyeloma therapy.
Subject must have documented disease progression during or after their last antimyeloma regimen.
Subject has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
Females of childbearing potential (FCBP) must:
a. Have two negative pregnancy tests as verified by the Investigator prior to starting study treatment. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. 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, 2 forms of contraception: one highly effective, and one additional effective (barrier) measure of contraception without interruption 28 days prior to starting study treatment, during the study treatment (including dose interruptions), and for at least 184 days after the last dose of CC-92480 or 28 days after the last dose of pomalidomide, or 7 months detailed in APPENDIX E for CC-92480 and APPENDIX F for pomalidomide. Note: A FCBP is a female who: 1) has achieved menarche at some point and, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy or amenorrhea due to other medical reasons 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).
- Male subjects must:
a. Practice true abstinence* (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 28 days after discontinuation of pomalidomide, or 94 days after the last dose of CC-92480, or 4 months after last dose of bortezomib, whichever is longer, even if he has undergone a successful vasectomy. Contraception requirements are detailed in APPENDIX E for CC-92480 and APPENDIX F for pomalidomide. * True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. [Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception].
Male subjects must agree to refrain from donating sperm while on study treatment, during dose interruptions and for at least 94 days following last dose of CC-92480, or 4 weeks following last dose of pomalidomide.
Females must agree to refrain from donating eggs while on study treatment and for at least 184 days after last dose of CC-92480.
Subjects must agree to refrain from donating blood while on study treatment, during dose interruptions and for at least 28 days following the last dose of study treatment.
All male and female subjects must follow all requirements defined in the Pregnancy Prevention Program in APPENDIX E for CC-92480 and APPENDIX F for pomalidomide.
Exclusion Criteria
Subject who has had progression during treatment or within 60 days of the last dose of a proteasome inhibitor.
For subjects with prior treatment of a bortezomib containing regimen, the best response achieved was not a minimal response (MR) or better, or subject discontinued bortezomib due to toxicity.
Subject who has had prior treatment with CC-92480 or pomalidomide.
Subject who has had any investigational agents within 28 days or 5 half-lives (whichever is shorter) of initiating study treatment
a. Participation in another interventional clinical trial concurrent with this study is not permitted, except for those who have completed treatment with the prior investigational agent(s) and are currently in Long-term Follow up.
- Subject has received any of the following:
a. Plasmapheresis within the last 28 days of initiating study treatment
b. Major surgery (as defined by the Investigator) within 28 days of initiating study treatment.
c. Radiation therapy, other than local palliative therapy, for myeloma associated bone lesions within 14 days of initiating study treatment.
d. Use of any systemic antimyeloma drug therapy within 14 days of initiating study treatment.
Subject has previously received allogeneic stem cell transplantation at any time during prior therapy or received autologous stem cell transplantation within 12 weeks of initiating study treatment.
Subject has plasma cell leukemia, Waldenstrom’s macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or clinically significant light-chain amyloidosis.
Subject with known central nervous system (CNS) involvement with myeloma.
Subject has any significant medical condition, including active or uncontrolled infection, presence of laboratory abnormality, or psychiatric illness that places the subject at an unacceptable risk for treatment-related complications, if he/she were to participate in the study.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 14 days for mild or asymptomatic infections or 28 days for severe/critical illness prior to initiating study treatment.
Acute symptoms must have resolved and there are no sequelae that would place the subject at a higher risk of receiving study treatment, based on Investigator assessment in consultation with the Sponsor Medical Monitor.
Subject has any condition that confounds the ability to interpret data from the study
Subject has any of the following laboratory abnormalities:
a. Absolute neutrophil count (ANC) < 1,000/μL. It is not permissible to administer GCSF to achieve minimum ANC levels within 7 days prior to screening complete blood count (CBC) (or within 14 days prior for pegfilgrastim).
b. Platelet count: < 75,000/μL for subjects in whom < 50% of bone marrow nucleated cells are plasma cells; or a platelet count < 50,000/μL for subjects in whom ≥ 50% of bone marrow nucleated cells are plasma cells (transfusions are not permitted within 7 days prior to screening CBC).
c. Hemoglobin < 8 g/dL (< 4.9 mmol/L).
d. Estimated glomerular filtration rate (eGFR) < 30 mL/min or requiring dialysis. eGFR will be calculated using the Modification of Diet in Renal Disease (MDRD) formula (see APPENDIX H).
e. Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L)
f. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × upper limit of normal (ULN)
g. Serum total bilirubin > 1.5 × ULN, or for participants with documented Gilbert’s syndrome > 3.0 mg/dL
Subject has peripheral neuropathy ≥ Grade 2
Subject with gastrointestinal disease or surgery (eg, gastric bypass surgery) that may significantly alter the absorption of CC-92480 and/or other oral study treatment.
Subject has prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years with the exception of the following noninvasive malignancies:
Basal cell carcinoma of the skin
Squamous cell carcinoma of the skin in situ (stage 0)
Carcinoma in situ of the cervix
Carcinoma in situ of the breast
Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is curative
- Subject has received immunosuppressive medication within the last 14 days of initiating study treatment. The following are exceptions to this criterion:
a. Intranasal, inhaled, topical or local corticosteroid injections (eg, intra-articular injection).
b. Systemic corticosteroids at doses that do not exceed 10 mg/day of prednisone or the equivalent (See Table 20).
c. Steroids as premedication for hypersensitivity reactions (eg, computed tomography [CT] scan premedication).
Administration of strong CYP3A modulators; administration of proton-pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole) within 2 weeks of starting study treatment.
Subject has impaired cardiac function or clinically significant cardiac disease, including any of the following:
a. Myocardial infarction within 1 year before randomization, or an unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure New York Heart Association Class III-IV)
b. Uncontrolled cardiac arrhythmia (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 5.0 Grade 2 or higher) or clinically significant electrocardiogram (ECG) abnormalities
Subject has uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment.
Subject who has had a live vaccine within 3 months of start of study therapy.
Subject is unable or unwilling to undergo protocol required thromboembolism or antiviral prophylaxis
Subject is positive for human immunodeficiency virus (HIV), chronic or active hepatitis B, active hepatitis A, or active hepatitis C:
a. Known positive HIV status. Refer to Section 6.1.
b. Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
c. Known to be seropositive for hepatitis C virus (HCV); anti-HCV antibody positive or HCV- ribonucleic acid (RNA) quantitation positive, except in the setting of a sustained virologic response (SVR), defined as viremia at least 12 weeks after completion of antiviral therapy.
Subject has a history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide (including ≥ Grade 3 rash during prior thalidomide or lenalidomide therapy), bortezomib or dexamethasone or the excipients contained in the formulations, or subject has any contraindications per local PI.
Subject is a female who is pregnant, nursing or breastfeeding, or who intends to become pregnant during participation in the study.
