Lenalidomide Versus Placebo in Myelodysplastic Syndromes With a Deletion 5q[31] Abnormality

Summary

The purpose of this study was to compare 2 doses (10 mg and 5 mg) of lenalidomide to that of placebo in subjects with red blood cell (RBC) transfusion-dependent low- or intermediate-1-risk IPSS MDS associated with a deletion (del) 5q\[31\] cytogenetic abnormality. Study participants were randomized to one of the two treatment groups or to placebo and took the study drug for 16 weeks. At this timepoint, participants were evaluated for erythroid response. If participants did not achieve at least a minor erythroid response, they were discontinued from the Double-Blind phase and entered into the Open-Label phase. All erythroid responders at Week 16 were to continue in the Double-Blind phase for up to 52 weeks. For participants that were still responding at the end of Double-Blind phase, they could then rollover into the Open-Label phase for an additional two years. Participants could remain on study for up to a total of 3 years. All participants who discontinued from the study were followed every 4 months for overall survival and progression to acute myeloid leukemia (AML).

Timeline

Start

2005-07

Primary completion

2008-06

Completion

2010-06

Publications

• Results Fenaux, Pierre, Giagounidis, Aristotle, Selleslag, Dominik, Beyne-Rauzy, Odile, Mufti, Ghulam J, Mittelman, Moshe, Muus, Petra, te Boekhorst, Peter, Sanz, Guillermo, del Canizo, Consuelo, Guerci-Bresler, Agnes, Schlegelberger, Brigitte, Aul, Carlo, Kreipe, Hans, Goehring, Gudrun, Knight, Robert, Francis, John, Fu, Tommy, Hellstrom-Lindberg, Eva. RBC Transfusion Independence and Safety Profile of Lenalidomide 5 or 10 mg in Pts with Low- or Int-1-Risk MDS with Del5q: Results From a Randomized Phase III Trial (MDS-004). ASH Annual Meeting Abstracts 2009 114: 944.
• Results Fenaux, P., Giagounidis, A., Selleslag, D. L., Beyne-Rauzy, O., Mittelman, M., Muus, P., Knight, R. D., Fu, T., Hellstrom-Lindberg, E., The MDS-004 Len del(5q) Study Group. Safety of lenalidomide (LEN) from a randomized phase III trial (MDS-004) in low-/int-1-risk myelodysplastic syndromes (MDS) with a del(5q) abnormality. J Clin Oncol (Meeting Abstracts) 2010 28: 6598
• Results Fenaux, P., Giagounidis, A., Selleslag, D., Knight, R., Fu, T., Hellström-Lindberg, E. Effect of baseline EPO and prior erythropoiesis stimulating agents on RBC transfusion independence in Low-/Int-1-Risk MDS with del 5q treated with lenalidomide: A randomized phase 3 study (MDS-004). Haematologica 2010; 95[suppl.2]:125, abs. 0311.
• Results Brandenburg, N., Fu, T., Revicki, D., Knight, R., Muus, P., Fenaux, P. Impact of lenalidomide on health-related quality of life in patients with RBC transfusion-dependent low- or int-1-risk myelodysplastic syndromes with del 5q: a randomized Phase 3 study (MDS-004). Haematologica 2010; 95[suppl.2]:127, abs. 0316
• Results Fenaux, P., Giagounidis, A., Beyne-Rauzy, O., Mufti, G., Mittelman, M., Muus, P., te Boekhorst, P., Sanz, G., Cazzola, M., Backstrom, J., Fu, T., Hellström-Lindberg, E. Prognostic Factors of Long-Term Outcomes In Low- or Int-1-Risk MDS with del5q Treated with Lenalidomide (LEN): Results From a Randomized Phase 3 Trial (MDS-004). Blood ASH Annual Meeting Abstracts 2010 116:21 abs. 4027.
• Results Brandenburg, N., Yu, R., Revicki, D. Reliability and Validity of the FACT-AN In Patients with Low or Int-1-Risk Myelodysplastic Syndromes with Deletion 5q. Blood ASH Annual Meeting Abstracts 2010 116:21 abs. 3827.
• Fenaux P, Giagounidis A, Selleslag D, Beyne-Rauzy O, Mittelman M, Muus P, Nimer SD, Hellstrom-Lindberg E, Powell BL, Guerci-Bresler A, Sekeres MA, Deeg HJ, Del Canizo C, Greenberg PL, Shammo JM, Skikne B, Yu X, List AF. Clinical characteristics and outcomes according to age in lenalidomide-treated patients with RBC transfusion-dependent lower-risk MDS and del(5q). J Hematol Oncol. 2017 Jun 26;10(1):131. doi: 10.1186/s13045-017-0491-2.
• Saft L, Karimi M, Ghaderi M, Matolcsy A, Mufti GJ, Kulasekararaj A, Gohring G, Giagounidis A, Selleslag D, Muus P, Sanz G, Mittelman M, Bowen D, Porwit A, Fu T, Backstrom J, Fenaux P, MacBeth KJ, Hellstrom-Lindberg E. p53 protein expression independently predicts outcome in patients with lower-risk myelodysplastic syndromes with del(5q). Haematologica. 2014 Jun;99(6):1041-9. doi: 10.3324/haematol.2013.098103. Epub 2014 Mar 28.
• Fenaux P, Giagounidis A, Selleslag D, Beyne-Rauzy O, Mufti G, Mittelman M, Muus P, Te Boekhorst P, Sanz G, Del Canizo C, Guerci-Bresler A, Nilsson L, Platzbecker U, Lubbert M, Quesnel B, Cazzola M, Ganser A, Bowen D, Schlegelberger B, Aul C, Knight R, Francis J, Fu T, Hellstrom-Lindberg E; MDS-004 Lenalidomide del5q Study Group. A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with del5q. Blood. 2011 Oct 6;118(14):3765-76. doi: 10.1182/blood-2011-01-330126. Epub 2011 Jul 13.
• Gohring G, Giagounidis A, Busche G, Hofmann W, Kreipe HH, Fenaux P, Hellstrom-Lindberg E, Schlegelberger B. Cytogenetic follow-up by karyotyping and fluorescence in situ hybridization: implications for monitoring patients with myelodysplastic syndrome and deletion 5q treated with lenalidomide. Haematologica. 2011 Feb;96(2):319-22. doi: 10.3324/haematol.2010.026658. Epub 2010 Nov 25.

Drugs

Indications