Carfilzomib, Lenalidomide, and Dexamethasone in New Multiple Myeloma Patients

Summary

Background: \- Carfilzomib is an experimental anti-cancer drug that has not yet been approved for treating multiple myeloma. Lenalidomide is a drug that may stop tumor growth and help the immune system kill cancer cells. Dexamethasone is a drug that helps stop inflammation. It is sometimes used to treat (alone or with other drugs) certain types of cancer, especially multiple myeloma. This combination of drugs has not been tested in people with multiple myeloma. Researchers want to see whether it is safe and effective for this group. Objectives: \- To test the effectiveness of combined carfilzomib, lenalidomide, and dexamethasone in treating multiple myeloma. Eligibility: \- People at least 18 years of age who have multiple myeloma that has not been treated. Design: * Participants will be screened with a medical history and physical exam. They will also have blood and urine tests, a bone marrow sample, and molecular imaging studies. * Participants will have eight 28-day cycles of treatment. The combined study drugs will be given as tablets and injections. Those in the study will be monitored with frequent blood tests, bone marrow samples, and molecular imaging studies. In addition to current standard measures to determine clinical responses, molecular tests will be conducted to define evidence of minimal residual disease. * After the first four cycles of therapy, those who are eligible for a stem cell transplant will have stem cells collected and stored for use if the cancer returns. * After stem cell collection, participants will have the second four treatment cycles. -, If the disease has improved or is stable at the end of eight cycles, those in the study may have another 12 cycles of low-dose (maintenance) lenalidomide alone. * Participants will have regular follow-up visits after the end of the study chemotherapy.

Timeline

Start

2011-07-21

Primary completion

2016-07-10

Completion

2020-09-24

Publications

• Background International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol. 2003 Jun;121(5):749-57.
• Background Kristinsson SY, Landgren O, Dickman PW, Derolf AR, Bjorkholm M. Patterns of survival in multiple myeloma: a population-based study of patients diagnosed in Sweden from 1973 to 2003. J Clin Oncol. 2007 May 20;25(15):1993-9. doi: 10.1200/JCO.2006.09.0100. Epub 2007 Apr 9.
• Background Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Zeldenrust SR, Dingli D, Russell SJ, Lust JA, Greipp PR, Kyle RA, Gertz MA. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008 Mar 1;111(5):2516-20. doi: 10.1182/blood-2007-10-116129. Epub 2007 Nov 1.
• Larrain CM, Victory JH, Desai PP, Friedman LR, Stepp H, Ashe R, Remmert K, Sinha S, Smith EC, Russell N, Pu T, Eade AV, Burke JF, Ho J, Yaffe MB, Kleiner DE, Schmidt K, Figg WD, Hernandez JM. A rebrand for proteasome inhibition in solid tumors via continuous hepatic artery infusion. JCI Insight. 2025 Nov 4;10(24):e199200. doi: 10.1172/jci.insight.199200. eCollection 2025 Dec 22.
• Landgren O, Kazandjian D, Roussel M, Jasielec J, Dytfeld D, Anderson A, Kervin TA, Iskander K, McFadden I, Jakubowiak AJ. Efficacy and safety of carfilzomib-lenalidomide-dexamethasone in newly diagnosed multiple myeloma: pooled analysis of four single-arm studies. Leuk Lymphoma. 2022 Oct;63(10):2413-2421. doi: 10.1080/10428194.2022.2068001. Epub 2022 May 12.
• Huang PA, Beedie SL, Chau CH, Venzon DJ, Gere S, Kazandjian D, Korde N, Mailankody S, Landgren O, Figg WD. Cereblon gene variants and clinical outcome in multiple myeloma patients treated with lenalidomide. Sci Rep. 2019 Oct 16;9(1):14884. doi: 10.1038/s41598-019-51446-9.
• Acosta-Alvear D, Cho MY, Wild T, Buchholz TJ, Lerner AG, Simakova O, Hahn J, Korde N, Landgren O, Maric I, Choudhary C, Walter P, Weissman JS, Kampmann M. Paradoxical resistance of multiple myeloma to proteasome inhibitors by decreased levels of 19S proteasomal subunits. Elife. 2015 Sep 1;4:e08153. doi: 10.7554/eLife.08153.
• Korde N, Roschewski M, Zingone A, Kwok M, Manasanch EE, Bhutani M, Tageja N, Kazandjian D, Mailankody S, Wu P, Morrison C, Costello R, Zhang Y, Burton D, Mulquin M, Zuchlinski D, Lamping L, Carpenter A, Wall Y, Carter G, Cunningham SC, Gounden V, Sissung TM, Peer C, Maric I, Calvo KR, Braylan R, Yuan C, Stetler-Stevenson M, Arthur DC, Kong KA, Weng L, Faham M, Lindenberg L, Kurdziel K, Choyke P, Steinberg SM, Figg W, Landgren O. Treatment With Carfilzomib-Lenalidomide-Dexamethasone With Lenalidomide Extension in Patients With Smoldering or Newly Diagnosed Multiple Myeloma. JAMA Oncol. 2015 Sep;1(6):746-54. doi: 10.1001/jamaoncol.2015.2010.

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Indications