A Phase III, Randomized, Open-label, 3-arm Study to Determine the Efficacy and Safety of Lenalidomide(REVLIMID) Plus Low-dose Dexamethasone When Given Until Progressive Disease or for 18 Four-week Cycles Versus the Combination of Melphalan, Prednisone, and Thalidomide Given for 12 Six-week Cycles in Patients With Previously Untreated Multiple Myeloma Who Are Either 65 Years of Age or Older or Not Candidates for Stem Cell Transplantation.
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
- MM diagnostic criteria (all 3 required):
- Monoclonal plasma cells in the bone marrow ≥10% and/or presence of a
- 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
- 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
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.
8. All patients must:
1. Have an understanding that the study drug could have a potential teratogenic
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
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).