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Currently, you can access the following clinical trials being conducted worldwide:
Clinicaltrials.gov identifier NCT04392037
Recruitment Status Not yet recruiting
First Posted May 18, 2020
Last update posted October 22, 2020
Evaluation of the effect iberdomide combined with low-dose cyclophosphamide and dexamethasone in patients with relapsed/refractory multiple myeloma.
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.
|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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, , Learn About Clinical Studies.-->
1. Age ≥ 18 years.
2. 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 (See Appendix A)
3. 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. 4. 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 ) 5. 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 (2.0x109/L circulating plasma cells
by standard differential) or Waldenstrom's macroglobulinemia
5. Subject has known meningeal involvement of multiple myeloma
6. Inadequate marrow reserve as defined by a platelet count <75 x 109/L or an absolute neutrophil count 13.5 mg/dL (>3.4 mmol/L)
8. 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.
9. Subject has received any of the following within the last 14 days of initiating
- 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
10. 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
11. 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:
- Intranasal, inhaled, topical or local steroid injections (eg, intra-articular
- 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)
12. 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
13. Creatinine clearance <30 ml/min or requirement of dialysis. 14. 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) 15. Significant hepatic dysfunction (total bilirubin ≥ 3 times normal value or transaminases ≥ 3 times normal value), unless related to myeloma 16. 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. 17. Subject known to test positive for human immunodeficiency virus (HIV), chronic or active hepatitis B, or active hepatitis A or C 18. Peripheral neuropathy of ≥grade 2. 19. Subjects with gastrointestinal disease that may significantly alter the absorption of CC-220 20. 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. 21. 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. 22. Subject is a female who is pregnant, nursing or breastfeeding, or who intends to become pregnant during the participation in the study 23. Subject is unable or unwilling to undergo protocol required thromboembolism prophylaxis 24. 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.
Contact: N.W.C.J van de Donk, Prof. MD PhD +31204444444 firstname.lastname@example.org
Contact: C.L.B.M. Korst, MD +31204444444 email@example.com
Amsterdam UMC, location AMC
Amsterdam UMC, location VUmc
Albert Schweitzer Ziekenhuis
VU University Medical Center
Principal Investigator: N.W.C.J van de Donk, Prof. MD PhD Amsterdam UMC, location VUmc