A Study to Compare MPR With MP in Newly Diagnosed Multiple Myeloma Subjects 65 Years Old or Older.
Condition: Newly Diagnosed Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Lenalidomide: Double-blind Induction; Melphalan; Prednisone; Aspirin; Placebo; Lenalidomide: Double-blind Maintenance; Lenalidomide: Open-label
Intervention description: Double-blind Induction: the starting lenalidomide oral dosing regimen was 10 mg once daily on Days 1 through 21 of each 28 day cycle for up to 9 cycles. Dose was reduced if needed due to dose-limiting toxicity.; Double-blind Induction: the starting melphalan oral dosing regimen in all 3 treatment arms was 0.18 mg/kg daily on Days 1 through 4 of each 28-day cycle for up to 9 cycles. Dose was reduced if needed due to dose-limiting toxicity.; Double-blind induction: the starting prednisone oral dosing regimen in all 3 treatment arms was 2 mg/kg daily on Days 1 through 4 of each 28-day cycle for up to 9 cycles. Dose was reduced if needed due to dose-limiting toxicity.; Double-blind induction: low-dose aspirin 75 mg to 100 mg daily for all treatment arms.
Double-blind maintenance: at the investigator's discretion; Double-blind induction: participants in treatment arm MPp+p received placebo once daily on Days 1 through 21 of each 28-day cycle for up to 9 cycles.
Double-blind maintenance: participants in treatment arms MPR+p and MPp+p received placebo once daily on Days 1 through 21 of each 28-day cycle from cycle 10 to disease progression.; Single-agent oral lenalidomide 10 mg once daily on Days 1 through 21 of each 28-day cycle from cycle 10 to disease progression.; Any study participant who had progressive disease had the option of open-label lenalidomide up to 25 mg daily on Days 1 through 21 of each 28-day cycle.
Intervention MeSH terms: Aspirin; Prednisone; Lenalidomide; Melphalan
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 459.0
Sex: All
Minimum age: 65 Years
Healthy volunteers: No
Keywords: Newly Diagnosed Multiple Myeloma; Celgene; CC-5013; Revlimid; Lenalidomide; Melphalan; Prednisone; Elderly

Summary:

      The purpose of this study is to determine whether lenalidomide is safe and effective in the
      treatment of patients with newly diagnosed Multiple Myeloma who are 65 years of age or older.
    

Eligibility criteria:

        Inclusion Criteria

          1. Must understand and voluntarily sign an informed consent form

          2. Age greater than or equal to 65 years at the time of signing the informed consent

          3. Newly diagnosed with symptomatic multiple myeloma as defined by the 3 criteria below:

        MM diagnostic criteria (all of next 3 required)

          1. Monoclonal plasma cells in the bone marrow greater than or equal to 10% and/or
             presence of a biopsy-proven plasmacytoma

          2. Monoclonal protein present in the serum and/or urine

          3. Myeloma-related organ dysfunction (at least one of the following) [C] Calcium
             elevation in the blood (serum calcium >10.5mg/dl or upper limit of normal) [R] Renal
             insufficiency (serum creatinine >2mg/dl) [A] Anemia (hemoglobin <10g/dl or 2g <
             normal) [B] Lytic bone lesions or osteoporosis AND have measurable disease as defined
             by the following; IgG multiple myeloma: Serum monoclonal paraprotein (M-protein) level
             greater than or equal to 1.0 g/dL or urine M-protein level greater than or equal to
             200 mg/24 hours IgA multiple myeloma: Serum M-protein level greater than or equal to
             0.5 g/dL or urine M-protein level greater than or equal to 200 mg/24 hours IgD
             multiple myeloma: Serum M-protein level greater than or equal to 0.05 g/dL or urine
             M-protein level greater than or equal to 200 mg/24 hours Light chain multiple myeloma:
             Serum M-protein level greater than or equal to 1.0 g/dL or urine M-protein level
             greater than or equal to 200 mg/24 hours IgM multiple myeloma (IgM M-protein plus
             lytic bone disease documented by skeletal survey plain films): Serum M-protein level
             greater than or equal to 1.0g/dL or urine M-protein level greater than or equal to
             200mg/24hours

          4. Karnofsky performance status greater than or equal to 60%.

          5. Able to adhere to the study visit schedule and other protocol requirements.

          6. Women of Childbearing potential (WCBP) must:

             a. Have a negative medically supervised pregnancy test prior to the start of study
             therapy. She must agree to ongoing pregnancy testing during the course of the study,
             and after end of study therapy. This applies even if the subject practices and
             continues sexual abstinence.

             b Either commit to 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 dose interruptions), and for 28 days after discontinuation of
             study therapy.

          7. Males Subjects must:

               1. Agree to use a condom during sexual contact with a WCBP, even if they have had a
                  vasectomy, throughout study drug therapy, during any dose interruption and after
                  the cessation of study therapy.

               2. Agree to not donate semen during study drug therapy and for a period after end of
                  study drug therapy.

          8. All subjects must

               1. Have an understanding that the study drug could have 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.

               4. All patients must be counseled about pregnancy precautions and risks of fetal
                  exposure.

        Female Subjects:

        Females of childbearing potential (FCBP) with regular cycles must agree to have pregnancy
        tests weekly for the first 28 days of study participation and then every 28 days while on
        study, at study discontinuation, and at day 28 following discontinuation from the study. If
        menstrual cycles are irregular, the pregnancy testing must occur weekly for the first 28
        days and then every 14 days while on study, at study discontinuation, and at days 14 and 28
        following discontinuation from the study.

        In addition to the required pregnancy testing, the Investigator must confirm with FCBP that
        she is continuing to use two reliable methods of birth control at each visit. Counseling
        about pregnancy precautions and the potential risks of fetal exposure must be conducted at
        a minimum of every 28 days. During counseling, subjects must be reminded to not share study
        drug and to not donate blood.

        Pregnancy testing and counseling must be performed if a subject misses her period or if her
        pregnancy test or her menstrual bleeding is abnormal. Study drug treatment must be
        discontinued during this evaluation.

        Females must agree to abstain from breastfeeding during study participation and for at
        least 28 days after the discontinuation from the study.

        Male Subjects:

        Counseling about the requirement for latex condom use during sexual contact with females of
        childbearing potential and the potential risks of fetal exposure must be conducted at a
        minimum of every 28 days. During counseling, subjects must be reminded to not share study
        drug and to not donate blood, sperm, or semen.

        If pregnancy or a positive pregnancy test does occur in a study subject or the partner of a
        study subject during study participation, study drug must be immediately discontinued.

        Exclusion Criteria

          1. Previous treatment with antimyeloma 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 28 days [4 weeks] of randomization]).

          2. Any serious medical condition, including the presence of laboratory abnormalities,
             which places the subject at an unacceptable risk if he or she participates in this
             study or confounds experimental the ability to interpret data from the study.

          3. Pregnant or lactating females.

          4. Radiotherapy within 14 days (2 weeks) of randomization.

          5. Plasmapheresis within 28 days (4 weeks) of randomization.

          6. Any of the following laboratory abnormalities:

             Absolute neutrophil count (ANC) < 1,500 cells/mL (1.5*10^9/L) Platelet count < 75,000
             cells/uL (75*10^9/L) for subjects in whom < 50% of bone marrow nucleated cells are
             plasma cells; but platelet count <30,000/uL for subjects in whom >= 50% of bone marrow
             nucleated cells are plasma cells Haemoglobin < 8.0 g/dL (80 g/L) Serum creatinine >
             2.5 mg/dL (221 µmol/L) Serum aspartate aminotransferase (SGOT/AST) or alanine
             aminotransferase (SGPT/ALT) > 3.0 times upper limit of normal (ULN)

          7. Prior history of malignancies, other than multiple myeloma, unless the subject has
             been free of the disease for greater than or equal to 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 histologic finding of
             prostate cancer (TNM Classification of Malignant Tumours (TNM) stage of T1a or T1b)

          8. Neuropathy of >= grade 2 severity.

          9. Known human immunodeficiency virus (HIV) positivity or active infectious hepatitis,
             type A, B or C.