Iberdomide Combined With Low-dose Cyclophosphamide and Dexamethasone (ICON)
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|ClinicalTrials.gov Identifier: NCT04392037|
Recruitment Status : Recruiting
First Posted : May 18, 2020
Last Update Posted : February 21, 2021
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma||Drug: Iberdomide plus low-dose cyclophosphamide and dexamethasone||Phase 2|
Novel drugs such as lenalidomide (an immunomodulatory drug; IMiD) have markedly improved the prognosis of multiple myeloma patients. Over the recent years, lenalidomide is increasingly used as part of first line therapy, typically until the development of progressive disease. These lenalidomide-refractory patients can be treated with several regimens. However, these regimens frequently contain proteasome inhibitors which are associated with neuropathy (bortezomib) or cardiovascular complications (carfilzomib). These proteasome inhibitors also need to be administered subcutaneously or intravenously in the hospital, once or twice per week. Also these regimens have limited efficacy in lenalidomide-refractory patients. This indicates that there is still an unmet medical need for new treatment options for patients who develop lenalidomide-refractory disease. These new treatment regimens should be active and safe without induction of neuropathy or cardiovascular side effects Moreover, an all oral regimen is frequently preferred by patients.
Iberdomide plus low-dose cyclophosphamide and dexamethasone
Available data indicates that the Cereblon E3 ligase modifying drug (CELMoD) iberdomide (CC220) is pharmacologically distinct from lenalidomide and pomalidomide with a higher potency against Cereblon, leading to differentiated antitumor and immunostimulating effects. Since iberdomide plus dexamethasone is active and well-tolerated in heavily pretreated patients including those with lenalidomide/pomalidomide-refractory disease, this two-drug regimen forms a new platform to which other agents can be added. The combinations of bortezomib, carfilzomib, or daratumumab plus iberdomide and dexamethasone are currently being evaluated.
Investigators have shown that low-dose cyclophosphamide can be effectively combined with the IMiDs lenalidomide and pomalidomide. These combinations are effective and are well-tolerated.
To address the unmet medical need for new treatment options for lenalidomide-refractory MM patients, the investigators aim at further improving the efficacy of IMiD/CELMoD plus dexamethasone combination therapy in terms of response and progression-free survival, by adding low-dose cyclophosphamide to the iberdomide-dexamethasone backbone (IberCd). This all-oral regimen will be tested in a lenalidomide-refractory patient population with 2-4 prior lines of therapy. The goal of this trial is to investigate the efficacy and safety of the IberCd combination in multiple myeloma patients who have refractory disease or a relapse after prior treatment with lenalidomide. Besides, various correlative studies will be performed during this trial including immune monitoring.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Patients will be treated with iberdomide plus low-dose cyclophosphamide and dexamethasone (IberCd)|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Study of CC220 (Iberdomide) Combined With Low-dose Cyclophosphamide and Dexamethasone in Relapsed/Refractory Multiple Myeloma (IberCd): ICON Study|
|Actual Study Start Date :||February 17, 2021|
|Estimated Primary Completion Date :||November 2023|
|Estimated Study Completion Date :||November 2023|
Experimental: Iberdomide plus low-dose cyclophosphamide and dexamethasone
Iberdomide 1.6mg on days 1-21
Low-dose Cyclophosphamide 50 mg on days 1-28 of each 28 day cycle
Dexamethasone 40 mg once weekly (20 mg in patients aged > 75 years)
Drug: Iberdomide plus low-dose cyclophosphamide and dexamethasone
Iberdomide, low dose Cyclophosphamide and Dexamethason will be given until progression or unacceptable toxicity
Other Name: CC-220
- Progression free survival [ Time Frame: up to 5 years ]PFS; i.e. time from the first dose of iberdomide-cyclophosphamide-dexamethasone to progression or death from any cause, whichever comes first
- Overall response rate [ Time Frame: up to 5 years ]In this analysis the investigators will consider the best response obtained during treatment according to the international myeloma working group (IMWG) criteria
- Safety and toxicity [ Time Frame: up to 5 years ]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
- Overall survival [ Time Frame: up to 5 years ]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.
- Time to response [ Time Frame: up to 5 years ]defined as time from first dose of iberdomide-cyclophosphamide-dexamethasone to the first objective documentation of PR or better.
- Duration of response [ Time Frame: up to 5 years ]defined as time from documentation of tumor response to disease progression.
- Time to second objective disease progression (PFS2) [ Time Frame: up to 5 years ]defined as time from first dose of iberdomide-cyclophosphamide-dexamethasone to 2nd disease progression or death from any cause.
- Time to next treatment (TTNT) [ Time Frame: up to 5 years ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04392037
|Contact: N.W.C.J van de Donk, Prof. MD PhDemail@example.com|
|Contact: C.L.B.M. Korst, MDfirstname.lastname@example.org|
|NWZ||Not yet recruiting|
|Contact: M Westerman|
|Amsterdam UMC, location AMC||Recruiting|
|Contact: J. Wegman, MD PhD|
|Amsterdam UMC, location VUmc||Recruiting|
|Contact: N.W.C.J van de Donk, Prof. MD PhD|
|Sub-Investigator: C.L.B.M. Korst, MD|
|Contact: E. van der Spek, MD PhD|
|Amphia Ziekenhuis||Not yet recruiting|
|Contact: M Van de Klift, MD PhD|
|Albert Schweitzer Ziekenhuis||Recruiting|
|Contact: M-D Levin, MD PhD|
|UMC Groningen||Not yet recruiting|
|Contact: W. Plattel, MD PhD|
|Contact: O. de Weerdt, MD PhD|
|Radboud UMC||Not yet recruiting|
|Contact: E.A. de Kort, MD|
|Principal Investigator:||N.W.C.J van de Donk, Prof. MD PhD||Amsterdam UMC, location VUmc|