A Study of CC-5013 Plus Dexamethasone Versus Dexamethasone Alone in Previously Treated Subjects With Multiple Myeloma

• Number of patients who survived [ Time Frame: Up to 23 months ] [ Designated as safety issue: Yes ]
  Time from randomization to death from any cause
• Number of participants with adverse events [ Time Frame: Up to 23 months ] [ Designated as safety issue: Yes ]
  Number of participants with adverse events
• Myeloma response rate [ Time Frame: Up to 23 months ] [ Designated as safety issue: No ]
  Myeloma response determination criteria developed by Bladé et al 1998
• Time to first symptomatic skeletal-related event (SRE) (clinical need for radiation or surgery to bone) [ Time Frame: Up to 23 months ] [ Designated as safety issue: No ]
  Time for randomization to the date of the first occurred of a symptomatic SRE (clinical need for radiotherapy or surgery to bone)
• Time to first worsening on the Eastern Cooperative Oncology Group (ECOG) performance scale [ Time Frame: Up to 23 months ] [ Designated as safety issue: No ]
  Time from randomization to the date of the first worsening compared to the last ECOG evaluation obtained prior to randomization

To compare the efficacy of oral CC-5013 in combination with oral pulse high-dose dexamethasone to that of placebo and oral high-dose pulse dexamethasone as treatment for subjects with relapsed or refractory multiple myeloma."

• Drug: CC-5013 plus dexamethasone
  25 mg daily for 21 days every 28 days.
  Other Names:

  • Revlimid
  • lenalidomide
• Drug: Dexamethasone plus Placebo
  Oral pulse dexamethasone is administered at a dose of 40mg daily on Days 1-4, 9-12, and 17-20 of each 28 day cycle for Cycles 1 through 4. Beginning with Cycle 5, the oral dexamethasone dosing schedule will be reduced to 40mg daily for Days 1-4 every 28 days. In addition, oral placebo capsules will be administered for 28 days of every cycle.
  Other Names:

  • Dexamethasone
  • Placebo

• Experimental: CC-5013 plus dexamethasone
  Arm A: Oral CC-5013 is initiated on Day 1 of Cycle 1 at a dose of 25 mg daily for 21 days every 28 days. Therefore, the subject will take a placebo identical in appearance to the CC-5013 capsule for week 4 of every 28 days. Oral pulse dexamethasone is administered at a dose of 40mg daily on Days 1-4, 9-12, and 17-20 of each 28 day cycle for Cycles 1 through 4. Beginning with Cycle 5, the oral dexamethasone dosing schedule will be reduced to 40mg daily for Days 1-4 every 28 days. In addition, oral CC-5013 placebo capsules will be administered for 28 days of every cycle.
  Intervention: Drug: CC-5013 plus dexamethasone
• Experimental: Dexamethasone plus placebo
  Arm B: Oral pulse dexamethasone is administered at a dose of 40mg daily on Days 1-4, 9-12, and 17-20 of each 28 day cycle for Cycles 1 through 4. Beginning with Cycle 5, the oral dexamethasone dosing schedule will be reduced to 40mg daily for Days 1-4 every 28 days. In addition, oral placebo capsules will be administered for 28 days of every cycle.
  Intervention: Drug: Dexamethasone plus Placebo

• Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau JL, Dmoszynska A, San Miguel J, Hellmann A, Facon T, Foà R, Corso A, Masliak Z, Olesnyckyj M, Yu Z, Patin J, Zeldis JB, Knight RD; Multiple Myeloma (010) Study Investigators. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007 Nov 22;357(21):2123-32.
• San-Miguel JF, Dimopoulos MA, Stadtmauer EA, Rajkumar SV, Siegel D, Bravo ML, Olesnyckyj M, Knight RD, Zeldis JB, Harousseau JL, Weber DM. Effects of lenalidomide and dexamethasone treatment duration on survival in patients with relapsed or refractory multiple myeloma treated with lenalidomide and dexamethasone. Clin Lymphoma Myeloma Leuk. 2011 Feb 1;11(1):38-43.
• Zangari M, Tricot G, Polavaram L, Zhan F, Finlayson A, Knight R, Fu T, Weber D, Dimopoulos MA, Niesvizky R, Fink L. Survival effect of venous thromboembolism in patients with multiple myeloma treated with lenalidomide and high-dose dexamethasone. J Clin Oncol. 2010 Jan 1;28(1):132-5. Epub 2009 Nov 9.
• Wang M, Dimopoulos MA, Chen C, Cibeira MT, Attal M, Spencer A, Rajkumar SV, Yu Z, Olesnyckyj M, Zeldis JB, Knight RD, Weber DM. Lenalidomide plus dexamethasone is more effective than dexamethasone alone in patients with relapsed or refractory multiple myeloma regardless of prior thalidomide exposure. Blood. 2008 Dec 1;112(12):4445-51. Epub 2008 Sep 17.

Inclusion Criteria:

• Prior or current diagnosis Durie-Salmon stage II or III multiple myeloma.
• Measurable levels of myeloma paraprotein in serum or urine (24-hour collection sample).
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0,1, or 2
• Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days of starting study drug

Exclusion Criteria:

• Prior development of disease progression during high-dose dexamethasone containing therapy
• Pregnant or lactating females
• The development of a desquamating rash while taking thalidomide
• Use of any standard/experimental anti-myeloma therapy within 28 days of randomization or use of any experimental non-drug therapy within 56 days of initiation of drug treatment
• Laboratory abnormalities: Absolute neutrophil count less than 1,000 cells/mm3
• Laboratory abnormalities: Platelet count < 75,000/mm3
• Laboratory abnormalities: Serum creatinine > 2.5 mg/dL
• Laboratory abnormalities: Serum Serum glutamic oxaloacetic transaminase (SGOT)/Aspartate aminotransferase (AST) or Serum glutamic pyruvic transaminase (SGPT)/Alanine aminotransferase (ALT) > 3.0 x upper limit of normal
• Laboratory abnormalities: Serum total bilirubin > 2.0 mg/dL
• Prior history of malignancies other than multiple myeloma unless the subject has been free of the disease for ≥ 3 years.