A clinical study that compares a treatment with Iberdomide, Daratumumab and Dexamethasone against a treatment with Daratumumab, Bortezomib, and Dexamethasone in patients with a non-responsive or progressive blood cancer called Multiple Myeloma
- Conditions
- Relapsed or Refractory Multiple Myeloma (RRMM)MedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-000431-49-BE
- Lead Sponsor
- Celgene Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 864
1.Subject is = 18 years of age at the time of signing the 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 anti-myeloma 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 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 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 (which must be reviewed on a monthly basis and source documented) or agree to use a condom (Appendix E) 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 has undergone a successful vasectomy.
13.Male subjects must agree to refrain from donating sperm while on study treatment, during dose interruptions and for at least 90 da
1.Subject has any significant medical condition
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) < 1,000/µL. It is not permissible to administer granulocyte colony-stimulating factor (GCSF) to achieve minimum ANC levels.
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. It is not permissible to transfuse subjects to achieve minimum platelet counts.
c.Hemoglobin < 8 g/dL (< 4.9 mmol/L).
d.Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2 or requiring dialysis. The eGFR can be calculated using the modified diet in renal disease (MDRD) formula.
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 = 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.
11.Subject has impaired cardiac function or clinically significant cardiac disease.
12.Subject received prior therapy with iberdomide.
13.Subject 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 anti-myeloma drug therapy within 14 days of initiating study treatment
14.Subject received any investigational agent within 28 days.
15.Subject has previously received a live vaccine within 3 months of initiating study treatment.
16.Concurrent administration of a strong inhibitor or inducer of cytochrome P450 (CYP3A4/5) (including within 14 days of initiating study treatment).
17.Subject is unable or unwilling to undergo protocol required thromboembolism or herpes zoster prophylaxis.
18.Subject has previously received allogeneic stem cell transplantation at any time d
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