Study to Determine Efficacy and Safety of Lenalidomide Plus Low-dose Dexamethasone Versus Melphalan, Prednisone, Thalidomide in Patients With Previously Untreated Multiple Myeloma
Study to Determine Efficacy and Safety of Lenalidomide Plus Low-dose Dexamethasone Versus Melphalan, Prednisone, Thalidomide in Patients With Previously Untreated Multiple Myeloma
The purpose of this study is to compare the safety and efficacy of Lenalidomide plus low dose
 dexamethasone to that of the combination of melphalan, prednisone and thalidomide.
CC-5013-MM020/IFM 07-01 is a Phase III, multicenter, randomized, open-label, 3-arm study that
 will compare the efficacy and safety of two Lenalidomide plus low-dose dexamethasone regimens
 given for two different durations of time (i.e., until progressive disease [PD] or for up to
 a maximum of 18 four-week cycles) to that of MPT given for a maximum of 12 six-week cycles.
Inclusion Criteria:

 1. Must understand and voluntarily sign informed consent form

 2. Age ≥ 18 years at the time of signing consent

 3. Previously untreated, symptomatic multiple myeloma as defined by the 3 criteria below:

 -  MM diagnostic criteria (all 3 required):

 -  Monoclonal plasma cells in the bone marrow ≥10% and/or presence of a
 biopsy-proven plasmacytoma

 -  Monoclonal protein present in the serum and/or urine

 -  Myeloma-related organ dysfunction (at least one of the following) [C] Calcium
 elevation in the blood (serum calcium >10.5 mg/dl or upper limit of normal) [R]
 Renal insufficiency (serum creatinine >2 mg/dl) [A] Anemia (hemoglobin <10 g/dl
 or 2 g < laboratory normal) [B] Lytic bone lesions or osteoporosis

 AND have measurable disease by protein electrophoresis analyses as defined by the
 following:

 -  IgG multiple myeloma: Serum monoclonal paraprotein (M-protein) level ≥ 1.0 g/dl
 or urine M-protein level ≥ 200 mg/24 hours

 -  IgA multiple myeloma: Serum M-protein level ≥ 0.5 g/dl or urine M-protein level ≥
 200 mg/24 hours

 -  IgM multiple myeloma (IgM M-protein plus lytic bone disease documented by
 skeletal survey plain films): Serum M-protein level ≥ 1.0 g/dl or urine M-protein
 level ≥ 200mg/24hours

 -  IgD multiple myeloma: Serum M-protein level ≥ 0.05 g/dl or urine M-protein level
 ≥ 200 mg/24 hours

 -  Light chain multiple myeloma: Serum M-protein level ≥ 1.0 g/dl or urine M-protein
 level ≥ 200 mg/24 hours

 AND are at least 65 years of age or older or, if younger than 65 years of age, are not
 candidates for stem cell transplantation because:

 -  The patient declines to undergo stem cell transplantation or

 -  Stem cell transplantation is not available to the patient due to cost or other
 reasons

 4. ECOG performance status of 0, 1, or 2

 5. Able to adhere to the study visit schedule and other protocol requirements

 6. Females of child-bearing potential (FCBP)^2:

 1. Must agree to undergo two medically supervised pregnancy tests prior to starting
 study therapy with either Rd or MPT. The first pregnancy test will be performed
 within 10-14 days prior to the start of Rd or MPT and the second pregnancy test
 will be performed within 24 hours prior to the start of Rd or MPT. She must also
 agree to ongoing pregnancy testing during the course of the study and after the
 end of study therapy. This applies even if the patient practices complete and
 continued sexual abstinence.

 2. Must commit to either continued abstinence from heterosexual intercourse (which
 must be reviewed on a monthly basis) or agree to use and be able to comply with
 effective contraception without interruption, 28 days prior to starting study
 drug, during the study therapy (including during periods of dose interruptions),
 and for 28 days after discontinuation of study therapy.

 7. Male Patients:

 1. Must agree to use a condom during sexual contact with a FCBP, even if they have
 had a vasectomy, throughout study drug therapy, during any dose interruption and
 after cessation of study therapy.

 2. Must agree to not donate semen during study drug therapy and for a period after
 end of study drug therapy.

 3. Must practice complete abstinence or agree to use a condom during sexual contact
 with a pregnant female or a female of childbearing potential while participating
 in the study, during dose interruptions and for at least 28 days following study
 drug discontinuation, even if he has undergone a successful vasectomy.

 8. All patients must:

 1. Have an understanding that the study drug could have a potential teratogenic
 risk.

 2. Agree to abstain from donating blood while taking study drug therapy and
 following discontinuation of study drug therapy.

 3. Agree not to share study medication with another person. All FCBP and male
 patients must be counseled about pregnancy precautions and risks of fetal
 exposure.

 Exclusion Criteria:

 1. Previous treatment with anti-myeloma therapy (does not include radiotherapy,
 bisphosphonates, or a single short course of steroid [i.e., less than or equal to the
 equivalent of dexamethasone 40 mg/day for 4 days; such a short course of steroid
 treatment must not have been given within 14 days of randomization]).

 2. Any serious medical condition that places the patient at an unacceptable risk if he or
 she participates in this study. Examples of such a medical condition are, but are not
 limited to, patient with unstable cardiac disease as defined by: Cardiac events such
 as MI within the past 6 months, NYHA heart failure class III-IV, uncontrolled atrial
 fibrillation or hypertension; patients with conditions requiring chronic steroid or
 immunosuppressive treatment, such as rheumatoid arthritis, multiple sclerosis and
 lupus, that likely need additional steroid or immunosuppressive treatments in addition
 to the study treatment.

 3. Pregnant or lactating females.

 4. Any of the following laboratory abnormalities:

 -  Absolute neutrophil count (ANC) < 1,000/µL (1.0 x 109/L)

 -  Untransfused platelet count < 50,000 cells/µL (50 x 10^9/L)

 -  Serum SGOT/AST or SGPT/ALT > 3.0 x upper limit of normal (ULN)

 5. Renal failure requiring hemodialysis or peritoneal dialysis.

 6. Prior history of malignancies, other than multiple myeloma, unless the patient has
 been free of the disease for ≥ 3 years. Exceptions include the following:

 -  Basal cell carcinoma of the skin

 -  Squamous cell carcinoma of the skin

 -  Carcinoma in situ of the cervix

 -  Carcinoma in situ of the breast

 -  Incidental histological finding of prostate cancer (TNM stage of T1a or T1b)

 7. Patients who are unable or unwilling to undergo antithrombotic therapy.

 8. Peripheral neuropathy of > grade 2 severity.

 9. Known HIV positivity or active infectious hepatitis, type A, B, or C. Primary AL
 (immunoglobulin light chain) amyloidosis and myeloma complicated by amyloidosis.

 -  1 A variety of other types of end organ dysfunctions can occasionally occur and
 lead to a need for therapy. Such dysfunction is sufficient to support
 classification as myeloma if proven to be myeloma-related.

 -  2 A FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or
 bilateral oophorectomy or 2) has not been naturally postmenopausal (i.e.,
 amenorrhea following cancer therapy does not rule out childbearing potential) for
 at least 24 consecutive months (i.e., has had menses at any time in the preceding
 24 consecutive months).