Health Condition 1: C900- Multiple myeloma
Conditions
Interventions
Intervention1: Treatment Arm A: IBERDOMIDE, DARATUMUMAB AND DEXAMETHASONE (IBERDD): Oral iberdomide at 1, 1.3 or 1.6 mg once daily from Days 1 to 21 of a 28-day cycle
Daratumumab administered as 1800
Sponsors
Celgene Corporation
PPD Pharmaceutical Development India Private Limited
Eligibility
Inclusion criteria
Inclusion criteria: Subjects must satisfy the following criteria to be enrolled in the study: 1. Subject is more than or equal to 18 years (there is no upper age limit) 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 more than or equal to 1 g/dL by serum protein electrophoresis (sPEP) or more than or equal to 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 one 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 anti-myeloma 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-containing 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 more than or equal to 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:
Exclusion criteria
Exclusion criteria: The presence of any of the following will exclude a subject from enrollment: 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. 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) b. Platelet count: c. Hemoglobin d. Estimated glomerular filtration rate (eGFR) 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 > 3.0 mg/dL for subjects with documented Gilbert’s syndrome. 5. Subject has plasma cell leukemia, Waldenstrom’s macroglobulinemia or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), 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 more than or equal to 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 - Steroids as premedication for hypersensitivity reactions 11. Subject has impaired cardiac function or clinically significant cardiac disease, including: a. Myocardial infarction within 1 year before randomization, or an unstable or uncontrolled disease/cond
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival (PFS)Timepoint: Time from randomization to the first documentation of progressive disease according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma 2016 or death due to any cause, whichever occurs first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Duration of response (DoR)Timepoint: Time from initial documented response (PR or better) until the first date the response criteria are met for PD or death due to any cause, whichever occurs first.;Minimal Residual Disease Negativity RateTimepoint: Sensitivity of a minimum of 1 in 10 raise to power of 5 nucleated cells by next generation flow cytometry in bone marrow aspirate for subjects who are CR or better per IMWG Uniform Response Criteria for Multiple Myeloma.;Overall response rate (ORR)Timepoint: Proportion of subjects who achieve PR or better response according to the IMWG criteria;Overall SurvivalTimepoint: Time from randomization to death from any cause. ;Progression-free survival 2 (PFS2)Timepoint: Time from randomization to documented disease progression on next-line therapy, or death from any cause, whichever occurs first.;Time to next treatment (TTNT)Timepoint: Time from randomization to the start of the subject receiving any anti-myeloma treatment other than study treatment. Subjects who do not start new anti-myeloma therapy are censored at the last assessment date or follow-up visit known to have not received new anti-myeloma treatment, whichever is later.;Time to progression (TTP)Timepoint: Time from randomization to the first documented disease progression.;Time to response (TTR)Timepoint: Time from randomization to the first documentation of response (PR or better). | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czech Republic, Denmark, Finland, France, Germany, Greece, India, Ireland, Israel, Italy, Japan, Mexico, Netherlands, Norway, Poland, Portugal, Republic of Korea, Spain, Sweden, Switzerland, Taiwan, Turkey, United Kingdom, United States of America
Contacts
Public ContactRashmi Chitgupi
PPD Pharmaceutical development Pvt Ltd.
Outcome results
None listed