A Randomized Phase III Study of CC-5013 Plus Dexamethasone Versus CC-5013 Plus Low Dose Dexamethasone in Multiple Myeloma With Thalidomide Plus Dexamethasone Salvage Therapy for Non-Responders
I. To evaluate the response rate and toxicity of CC-5013 (lenalidomide) plus dexamethasone
(standard dose) versus CC-5013 plus low dose dexamethasone in patients with newly diagnosed
myeloma at any time in the first 4 cycles of treatment and to determine if CC-5013 plus low
dose dexamethasone will have similar response rate with lower toxicity (First Phase).
I. To evaluate the response rate of thalidomide plus dexamethasone (Thal/Dex) in patients
with newly diagnosed myeloma who do not achieve a complete or partial response (as defined
in Section 6.2.1 and 6.2.2) at any time in the first 4 cycles with the CC-5013 and
dexamethasone combination in either of the two arms (First Phase).
II. To study the effect of CC-5013 on bone marrow microvessel density and angiogenesis
grade, on PCLI, and on the expression of vascular endothelial growth factor (VEGF) and basic
fibroblast growth factor (bFGF) in the marrow (First Phase).
III. To study the effect of CC-5013 and dexamethasone on bone marrow mesenchymal progenitor
cells (MPCs) (First Phase).
IV. To evaluate in a separate expansion phase (Addendum #6) the efficacy of aspirin (325
mg/day) versus Coumadin (dose adjusted to maintain a target INR of 2-3) in preventing DVT in
patients with newly diagnosed myeloma receiving CC-5013 plus standard dose dexamethasone.
This separate expansion phase of the trial that will start after accrual to the first phase
of the trial testing the primary objective listed above is completed.
OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2
Arm I: Patients receive oral lenalidomide once daily on days 1-21, oral acetylsalicylic acid
(or other deep vein thrombosis prophylaxis at the discretion of the principal investigator)
once daily on days 1-28, and standard-dose oral dexamethasone once daily on days 1-4, 9-12,
Arm II: Patients receive oral lenalidomide and acetylsalicylic acid as in arm I and low-dose
oral dexamethasone once daily on days 1, 8, 15, and 22.
In both arms, courses repeat every 28 days in the absence of unacceptable toxicity or
disease progression. Patients not responding at any point during the first 4 courses of
lenalidomide and dexamethasone are assigned to 1 of 2 salvage therapy arms. Patients who
progress during treatment on arms I or II have the option to register on salvage therapy
arms III or IV respectively.
Arm III (patients with no response after treatment on arm I): Patients receive oral
thalidomide once daily on days 1-28 and standard-dose oral dexamethasone once daily on days
1-4, 9-12, and 17-20.
Arm IV (patients with no response after treatment on arm II): Patients receive oral
thalidomide as in arm III and low-dose oral dexamethasone once daily on days 1, 8, 15, and
In both salvage therapy arms, courses repeat every 28 days in the absence of unacceptable
toxicity or disease progression. After completion of 4 courses of therapy, patients may
undergo stem cell harvest (using growth factors only) for cryopreservation.
Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then
annually for 2 years.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Response rate based on IBMTR/ABMTR
Up to 7 years
S. Vincent Rajkumar
Eastern Cooperative Oncology Group
United States: Food and Drug Administration
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