Iberdomide-dexamethasone Alone or in Combination With Standard MM Treatment Regimens in Transplant Ineligible Newly Diagnosed Patients.

Summary

This is a multicenter, phase II, national, and open-label study to evaluate the efficacy and safety of two different combinations, iberdomide-dexamethasone (IBERDEX) and iberdomide-dexamethasone in combination with daratumumab (IBERDARADEX) in transplant ineligible newly diagnosed multiple myeloma (NDMM) patients. It will be ensured that at least 30% of the patients are frail in order to evaluate the feasibility of these combinations in this special population. Patients will receive treatment with either iberdomide + dexamethasone (IBERDEX) or iberdomide + daratumumab + dexamethasone (IBERDARADEX), until unacceptable toxicity, disease progression, patient withdrawal, loss to follow-up, end of study or death, whichever comes first. This is not a randomized trial so eligible patients will be sequentially allocated to receive iberdomide-dexamethasone or iberdomide-dexamethasone plus daratumumab.

Timeline

Start

2022-12-15

Primary completion

2029-12

Completion

2029-12

Publications

• Background Mateos MV, San Miguel JF. Management of multiple myeloma in the newly diagnosed patient. Hematology Am Soc Hematol Educ Program. 2017 Dec 8;2017(1):498-507. doi: 10.1182/asheducation-2017.1.498.
• Background Durie BGM, Kumar SK, Usmani SZ, Nonyane BAS, Ammann EM, Lam A, Kobos R, Maiese EM, Facon T. Daratumumab-lenalidomide-dexamethasone vs standard-of-care regimens: Efficacy in transplant-ineligible untreated myeloma. Am J Hematol. 2020 Dec;95(12):1486-1494. doi: 10.1002/ajh.25963. Epub 2020 Sep 5.
• Background Belotti A, Ribolla R, Cancelli V, Crippa C, Bianchetti N, Ferrari S, Bottelli C, Cattaneo C, Tucci A, De La Fuente Barrigon C, Rossi G. Transplant eligibility in elderly multiple myeloma patients: Prospective external validation of the international myeloma working group frailty score and comparison with clinical judgment and other comorbidity scores in unselected patients aged 65-75 years. Am J Hematol. 2020 Jul;95(7):759-765. doi: 10.1002/ajh.25797. Epub 2020 Apr 23.
• Background Facon T, Dimopoulos MA, Meuleman N, Belch A, Mohty M, Chen WM, Kim K, Zamagni E, Rodriguez-Otero P, Renwick W, Rose C, Tempescul A, Boyle E, Manier S, Attal M, Moreau P, Macro M, Leleu X, Lorraine Chretien M, Ludwig H, Guo S, Sturniolo M, Tinel A, Silvia Monzini M, Costa B, Houck V, Hulin C, Yves Mary J. A simplified frailty scale predicts outcomes in transplant-ineligible patients with newly diagnosed multiple myeloma treated in the FIRST (MM-020) trial. Leukemia. 2020 Jan;34(1):224-233. doi: 10.1038/s41375-019-0539-0. Epub 2019 Aug 19.
• Background Cruz-Jentoft AJ, Gonzalez B, de la Rubia J, Hernandez Rivas JA, Soler JA, Fernandez Lago C, Arnao M, Gironella M, Perez Persona E, Zudaire MT, Olivier C, Altes A, Garcia Guinon A, Nomdedeu B, Arnan M, Ramirez Payer A, Sanchez-Godoy P, Pajuelo N, Vilanova D, Monjil DF, Bonanad S; GAH Group. Further psychometric validation of the GAH scale: Responsiveness and effect size. J Geriatr Oncol. 2017 May;8(3):211-215. doi: 10.1016/j.jgo.2016.12.008. Epub 2016 Dec 22.
• Background Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, Rabin N, Orlowski RZ, Komarnicki M, Suzuki K, Plesner T, Yoon SS, Ben Yehuda D, Richardson PG, Goldschmidt H, Reece D, Lisby S, Khokhar NZ, O'Rourke L, Chiu C, Qin X, Guckert M, Ahmadi T, Moreau P; POLLUX Investigators. Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016 Oct 6;375(14):1319-1331. doi: 10.1056/NEJMoa1607751.
• Background Bahlis NJ, Dimopoulos MA, White DJ, Benboubker L, Cook G, Leiba M, Ho PJ, Kim K, Takezako N, Moreau P, Kaufman JL, Krevvata M, Chiu C, Qin X, Okonkwo L, Trivedi S, Ukropec J, Qi M, San-Miguel J. Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study. Leukemia. 2020 Jul;34(7):1875-1884. doi: 10.1038/s41375-020-0711-6. Epub 2020 Jan 30.
• Background Dimopoulos MA, San-Miguel J, Belch A, White D, Benboubker L, Cook G, Leiba M, Morton J, Ho PJ, Kim K, Takezako N, Moreau P, Kaufman JL, Sutherland HJ, Lalancette M, Magen H, Iida S, Kim JS, Prince HM, Cochrane T, Oriol A, Bahlis NJ, Chari A, O'Rourke L, Wu K, Schecter JM, Casneuf T, Chiu C, Soong D, Sasser AK, Khokhar NZ, Avet-Loiseau H, Usmani SZ. Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of POLLUX. Haematologica. 2018 Dec;103(12):2088-2096. doi: 10.3324/haematol.2018.194282. Epub 2018 Sep 20.
• Background Facon T, Kumar S, Plesner T, Orlowski RZ, Moreau P, Bahlis N, Basu S, Nahi H, Hulin C, Quach H, Goldschmidt H, O'Dwyer M, Perrot A, Venner CP, Weisel K, Mace JR, Raje N, Attal M, Tiab M, Macro M, Frenzel L, Leleu X, Ahmadi T, Chiu C, Wang J, Van Rampelbergh R, Uhlar CM, Kobos R, Qi M, Usmani SZ; MAIA Trial Investigators. Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. N Engl J Med. 2019 May 30;380(22):2104-2115. doi: 10.1056/NEJMoa1817249.
• Background Perrot A, Facon T, Plesner T, Usmani SZ, Kumar S, Bahlis NJ, Hulin C, Orlowski RZ, Nahi H, Mollee P, Ramasamy K, Roussel M, Jaccard A, Delforge M, Karlin L, Arnulf B, Chari A, He J, Ho KF, Van Rampelbergh R, Uhlar CM, Wang J, Kobos R, Gries KS, Fastenau J, Weisel K. Health-Related Quality of Life in Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma: Findings From the Phase III MAIA Trial. J Clin Oncol. 2021 Jan 20;39(3):227-237. doi: 10.1200/JCO.20.01370. Epub 2020 Dec 16.
• Background Ito T, Handa H. [Cereblon as a primary target of IMiDs]. Rinsho Ketsueki. 2019;60(9):1013-1019. doi: 10.11406/rinketsu.60.1013. Japanese.
• Background Bjorklund CC, Kang J, Amatangelo M, Polonskaia A, Katz M, Chiu H, Couto S, Wang M, Ren Y, Ortiz M, Towfic F, Flynt JE, Pierceall W, Thakurta A. Iberdomide (CC-220) is a potent cereblon E3 ligase modulator with antitumor and immunostimulatory activities in lenalidomide- and pomalidomide-resistant multiple myeloma cells with dysregulated CRBN. Leukemia. 2020 Apr;34(4):1197-1201. doi: 10.1038/s41375-019-0620-8. Epub 2019 Nov 12. No abstract available.
• Background Matyskiela ME, Zhang W, Man HW, Muller G, Khambatta G, Baculi F, Hickman M, LeBrun L, Pagarigan B, Carmel G, Lu CC, Lu G, Riley M, Satoh Y, Schafer P, Daniel TO, Carmichael J, Cathers BE, Chamberlain PP. A Cereblon Modulator (CC-220) with Improved Degradation of Ikaros and Aiolos. J Med Chem. 2018 Jan 25;61(2):535-542. doi: 10.1021/acs.jmedchem.6b01921. Epub 2017 Apr 20.
• Background Burtis CA, Ashwood ER. Tietz Textbook of Clinical Chemistry, 3rd ed. Philadelphia; WB Saunders, 1998.

Drugs

Indications