Multiple Myeloma
Conditions
Interventions
Stage 1 Treatment Arms A1, A2 and A3 and Stage 2 Arm A (iberdomide, daratumumab
and dexamethasone):
- Oral iberdomide at 1, 1.3 and 1.6 mg once daily from Days 1 to 21 of a 28-day
cycle
- Daratumuma
Sponsors
Celgene Corporation
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 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. Subject has documented diagnosis of MM and measurable disease, defined as any of the following: a. M-protein quantities >= 1 g/dL by serum protein electrophoresis (sPEP) or >= 200 mg/24-hour urine collection by urine protein electrophoresis (uPEP); or b. Light chain MM without measurable disease in serum or urine: serum free light chain (FLC) levels > 100 mg/L (10 mg/dL) involved light chain and an abnormal kappa/lambda FLC ratio 5. Subject has received 1 to 2 prior lines of anti-myeloma therapy. 6. Subject achieved a response (partial response [PR] or better) to at least 1 prior antimyeloma regimen. 7. Subject must have documented disease progression during or after their last antimyeloma regimen. 8. Prior treatment with CD38-directed therapy: In Stage 1, subjects with prior CD38-directed therapy are not eligible. In Stage 2, prior treatment with CD38-directed therapy is permitted only if all the following are fulfilled: a. Best response achieved during CD38-directed therapy was > PR. b. Subject did not progress while receiving CD38-directed therapy or within 60 days of last dose of therapy. c. Subject did not discontinue CD38-directed therapy due to a related AE. d. Last dose of daratumumab was >= 3 months prior to randomization. 9. .Prior treatment with bortezomib therapy is permitted, if all the following are fulfilled: a.Best response achieved during bortezomib-containing therapy was at least a minimal response (MR). b.Subject did not progress while receiving bortezomib therapy or within 60 days of last dose of therapy. 10.Subject has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2. 11. 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 28 days after the last dose of iberdomide, 3 months after the last dose of daratumumab or 7 months after the last dose of bortezomib, whichever is longest. 12. Male subjects must: a. Practice true abstinence 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 90 days after the last dose of iberdomide, 3 months after the last dose of daratumumab, or 4 months after the last dose of bortezomib, whichever is longer even if he <
Exclusion criteria
Exclusion criteria: 1. 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. 2. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 14 days for mild or asymptomatic infections or within 28 days for severe/critical illness prior to randomization. Acute symptoms must have resolved and there must be no sequelae that would place the subject at a higher risk of clinically significant complications from receiving study treatment, based on the Investigator*s assessment in consultation with the Sponsor Medical Monitor. 3. Subject has any condition that confounds the ability to interpret data from the study. 4. Subject has any of the following laboratory abnormalities: a. Absolute neutrophil count (ANC) = 50% of bone marrow nucleated cells are plasma cells. It is not permissible to transfuse subjects to achieve minimum platelet counts. c. Hemoglobin 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 > 3.0 mg/dL for subjects with documented Gilbert*s syndrome. 5. Subject has plasma cell leukemia, Waldenstrom*s macroglobulinemia or POEMS syndrome ), or clinically significant amyloidosis. 6. Subject has peripheral neuropathy Grade 3, Grade 4 or Grade 2 with pain. 7. Subject has gastrointestinal disease that may significantly alter the absorption of iberdomide and/or other oral study treatment. 8. 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 9. Subject with known central nervous system involvement with MM. 10. Subject has received immunosuppressive medication within the last 14 days of initiating study treatment. The following are exceptions to this criterion: • Intranasal, inhaled, topical or local corticosteroid injections (eg, intra-articular • injection) • Systemic corticosteroids at doses that do not exceed 10 mg/day of prednisone (or an • equivalent dose of an alternative glucocorticoid, see Table 7) • Steroids as premedication for hypersensitivity reactions (eg, computed tomography [CT] scan
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overview of Key Efficacy Assessments • Myeloma paraprotein (serum and 24-hour urine) • Serum immunofixation • Serum immunoglobulins • Serum free light chains • Bone marrow aspiration/biopsy • Percent plasma cells in the bone marrow • Radiographic assessments of lytic bone lesions • Extramedullary plasmacytoma (EMP) assessments • Minimal residual disease assessment • Response per International Myeloma Working Group (IMWG) criteria Overview of Key Safety Assessments • Adverse events (AEs) • Complete physical examination including vital signs and venous thromboembolism • (VTE) monitoring • Clinical laboratory evaluations (hematology, chemistry) • Electrocardiogram (ECG) • Pregnancy testing/counselling • Concomitant medications and procedures | — |
Countries
Netherlands
Outcome results
None listed