IBERDOMIDE for Relapsed/refractory multiple myeloma

Inclusion criteria

• {"criterion_text":"-Age ≥ 18 years."}
• {"criterion_text":"-WHO performance 0, 1, or 2"}
• {"criterion_text":"-Life expectancy at least 3 months"}
• {"criterion_text":"-A female of childbearing potential (FCBP) is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) and 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 two forms of contraception: one highly effective, and one additional effective (barrier) measure of contraception without interruption 28 days prior to starting investigational product, during the study treatment (including dose interruptions), and for at least 28 days after the last dose of CC-220, 90 days after the last dose of cyclophosphamide, whichever is longer."}
• {"criterion_text":"-Written informed consent"}
• {"criterion_text":"-Male subjects must: a. Practice true abstinence (which must be reviewed on a monthly basis and source documented) 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 following the last dose of study treatment, even if he has undergone a successful vasectomy"}
• {"criterion_text":"-All 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."}
• {"criterion_text":"-All male and female subjects must follow all requirements defined in the Pregnancy Prevention Program (v5.1). See Appendix H for CC-220 Pregnancy Prevention Plan for Subjects in Clinical Trials."}
• {"criterion_text":"-Males must agree to refrain from donating sperm while on study treatment, during dose interruptions and for at least 90 days following last dose of study treatment."}
• {"criterion_text":"-Subject must have documented diagnosis of multiple myeloma and have measurable disease as defined by any of the following: • Serum monoclonal paraprotein (M-protein) level ≥5 g/L (0.5 g/dL); or urine M-protein level ≥200 mg/24 hours; or serum immunoglobulin free light chain ≥100 mg/L (10 mg/dL) and abnormal serum immunoglobulin kappa lambda free light chain ratio"}
• {"criterion_text":"-Relapsed or refractory disease. Relapse is defined as progression of disease after an initial response to previous treatment, more than 60 days after cessation of treatment. Refractory disease is defined as <50% reduction in M-protein or progression of disease during treatment or within 60 days after cessation of treatment."}
• {"criterion_text":"-Subject had 2-4 prior anti-myeloma regimens. (Note: Induction, bone marrow transplant with or without maintenance therapy is considered one regimen; Prior pomalidomide is allowed )"}
• {"criterion_text":"-Subject has developed lenalidomide-refractory disease (any dose) during prior treatment with lenalidomide or a lenalidomide-containing regimen Lenalidomide-refractory MM is defined as progressive disease during therapy, no response (< PR) to prior lenalidomide-containing therapy, or progression within 60 days of discontinuation from lenalidomide-containing regimens, according to the IMWG criteria."}

Exclusion criteria

• {"criterion_text":"-Subjects who previously received continuous low-dose cyclophosphamide alone or in combination with other anti-MM agents are excluded (cyclophosphamide once weekly such as in bortezomib-cyclophospahmide-dexametahsone regimen (VCD) is allowed)."}
• {"criterion_text":"-Inadequate marrow reserve as defined by a platelet count <75 x 109/L or an absolute neutrophil count <1.0 x 109/L"}
• {"criterion_text":"-Corrected serum calcium >13.5 mg/dL (>3.4 mmol/L)"}
• {"criterion_text":"-Subject has a history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide, pomalidomide, dexamethasone, or cyclophosphamide. Subject has known or suspected hypersensitivity to the excipients contained in the formulation of iberdomide, dexamethasone, or cyclophosphamide."}
• {"criterion_text":"-Subject has current or prior use of immunosuppressive medication within 14 days prior to the first dose of IP. The following are exceptions to this criterion: Protocol: ICON study, Version number: 4, date October 14, 2020 26 of 117 - Intranasal, inhaled, topical or local steroid injections (eg, intra-articular injection) - Systemic corticosteroids at physiologic doses that do not exceed 10 mg/day of prednisone or equivalent - Steroids as premedication for hypersensitivity reactions (eg, computed tomography [CT] scan premedication)"}
• {"criterion_text":"-Subject has taken a strong inhibitor or inducer of CYP3A4/5 including grapefruit, St. John’s Wort or related products within two weeks prior to dosing and during the course of study"}
• {"criterion_text":"-Subject known to test positive for human immunodeficiency virus (HIV), chronic or active hepatitis B, or active hepatitis A or C"}
• {"criterion_text":"-Non-secretory MM"}
• {"criterion_text":"-Subject has known meningeal involvement of multiple myeloma"}
• {"criterion_text":"-Creatinine clearance <45 ml /min or requirement of dialysis."}
• {"criterion_text":"-Significant hepatic dysfunction (total bilirubin >3 times normal value or transaminases > 3 times normal value), unless related to multiple myeloma"}
• {"criterion_text":"-Peripheral neuropathy of ≥grade 2."}
• {"criterion_text":"-Subject has any concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, respiratory disease, infection, hypertension, etc.) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study"}
• {"criterion_text":"-Subjects with gastrointestinal disease that may significantly alter the absorption of CC-220"}
• {"criterion_text":"-Subject is known or suspected of not being able to comply with the study protocol (eg, because of alcoholism, drug dependency, or psychological disorder) or the subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise their well-being) or that could prevent, limit, or confound the protocol-specified assessments"}
• {"criterion_text":"-Subject is a female who is pregnant, nursing or breastfeeding, or who intends to become pregnant during the participation in the study"}
• {"criterion_text":"-Subject is unable or unwilling to undergo protocol required thromboembolism prophylaxis"}
• {"criterion_text":"-Subject has received any of the following within the last 14 days of initiating IberCd: - Plasmapheresis - Major surgery (as defined by the Investigator) - Radiation therapy other than local therapy for MM associated bone lesions - Use of any systemic myeloma drug therapy"}
• {"criterion_text":"-Subject has been treated with an investigational agent (ie, an agent not commercially available) within 28 days or 5 half-lives (whichever is longer) of initiating IberCd treatment"}
• {"criterion_text":"-Systemic AL amyloidosis or plasma cell leukemia (>2.0x109/L circulating plasma cells by standard differential) or Waldenstrom's macroglobulinemia"}
• {"criterion_text":"-Uncontrolled or severe cardiovascular disease (NYHA class III or IV heart failure; myocardial infarction within the last 6 months of study entry); unstable angina; unstable cardiac arrhythmias; clinically significant pericardial disease)"}
• {"criterion_text":"-History of active malignancy during the past 3 years, except squamous cell and basal cell carcinomas of the skin and carcinoma in situ of the cervix or breast and incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is cured, or malignancy that in the opinion of the local investigator, with concurrence with the principal investigator, is considered cured with minimal risk of recurrence within 3 years."}
• {"criterion_text":"-Subject has previously received an allogeneic stem cell transplantation within 1 year before the date of registration and has not used immunosuppressive drugs within one month before the date of registration."}
• {"criterion_text":"-Treatment with prior iberdomide"}

Primary endpoints

• {"endpoint_text":"-Progression free survival (PFS; i.e. time from the first dose of iberdomide-cyclophosphamide-dexamethasone to progression or death from any cause, whichever comes first)","definition_or_measurement_approach":"Time from the first dose of iberdomide-cyclophosphamide-dexamethasone to progression or death from any cause, whichever comes first (as stated)."}

Secondary endpoints

• {"endpoint_text":"-Overall response rate. In this analysis we will consider the best response obtained during treatment according to the international myeloma working group (IMWG) criteria","definition_or_measurement_approach":"Best response obtained during treatment according to IMWG criteria (as stated)."}
• {"endpoint_text":"-Safety and toxicity as defined by type, frequency and severity of adverse events as defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03","definition_or_measurement_approach":"Adverse events classified by type, frequency and severity using NCI CTCAE v4.03 (as stated)."}
• {"endpoint_text":"-Overall survival measured from first dose of iberdomide-cyclophosphamide-dexamethasone, to time of death from any cause. Patients still alive or lost to follow up are censored at the date they were last known to be alive.","definition_or_measurement_approach":"Time from first dose to death from any cause; censoring at last known alive date (as stated)."}
• {"endpoint_text":"-Time to response defined as time from first dose of iberdomide-cyclophosphamidedexamethasone to the first objective documentation of PR or better.","definition_or_measurement_approach":"Time from first dose to first objective documentation of PR or better (as stated)."}
• {"endpoint_text":"-Duration of response defined as time from documentation of tumor response to disease progression.","definition_or_measurement_approach":"Time from documentation of tumor response to disease progression (as stated)."}
• {"endpoint_text":"-Time to second objective disease progression (PFS2) defined as time from first dose of iberdomide-cyclophosphamide-dexamethasone to 2nd disease progression or death from any cause.","definition_or_measurement_approach":"Time from first dose to second disease progression or death (as stated)."}
• {"endpoint_text":"-Time to next treatment (TTNT) defined as the date from first dose of iberdomide- cyclophosphamide-dexamethasone to first day when subject receives another myeloma treatment. Subjects who do not start new myeloma therapy are censored at the last known alive date or first dose date, whichever is later.","definition_or_measurement_approach":"Time from first dose to first day subject receives another myeloma treatment; censoring rules as stated."}

Netherlands

Earliest CTIS Part Ii Submission Date

25-11-2024

Latest Decision Or Authorization Date

28-11-2024

Processing Time Days

3

Number Of Sites

9

Number Of Participants

60

Primary sponsor

Full Name

Amsterdam UMC

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands

Third parties

• {"country":"","full_name":"Amsterdam UMC","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"Celgene BV","duties_or_roles":"Monetary support","organisation_type":""}