Lenalidomide and Dexamethasone With or Without Thalidomide in Treating Patients With Multiple Myeloma
Condition: DS Stage I Multiple Myeloma; DS Stage II Multiple Myeloma; DS Stage III Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Dexamethasone; Laboratory Biomarker Analysis; Lenalidomide; Thalidomide
Intervention description: Given PO; Optional correlative studies; Given PO; Given PO
Intervention MeSH terms: Thalidomide; Dexamethasone; Dexamethasone acetate; Lenalidomide; Ichthammol; BB 1101
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 452.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase III trial studies lenalidomide and low-dose dexamethasone to see how
      well it works compared to lenalidomide and standard-dose dexamethasone, given with or without
      thalidomide, in treating patients with multiple myeloma. Biological therapies, such as
      lenalidomide, may stimulate the immune system in different ways and stop cancer cells from
      growing. Lenalidomide and thalidomide may also stop the growth of multiple myeloma by
      blocking blood flow to the cancer. Drugs used in chemotherapy, such as dexamethasone, work in
      different ways to stop the growth of cancer cells, either by killing the cells or by stopping
      them from dividing. Giving lenalidomide, thalidomide, and dexamethasone together may kill
      more cancer cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must be diagnosed with symptomatic multiple myeloma within the past 90 days
             confirmed by the following:

               -  Bone marrow plasmacytosis with >= 10% plasma cells or sheets of plasma cells or
                  biopsy proven plasmacytoma which must be obtained within 4 weeks prior to
                  randomization

               -  Measurable levels of monoclonal protein (M protein): >= 1.0 g/dL on serum protein
                  electrophoresis or >= 200 mg of monoclonal light chain on a 24 hour urine protein
                  electrophoresis which must be obtained within 4 weeks prior to randomization;
                  both serum protein electrophoresis (SPEP) and urine protein electrophoresis
                  (UPEP) are required to be performed within 28 days prior to randomization; please
                  note that if both serum and urine m-components are present, both must be followed
                  in order to evaluate response

          -  Hemoglobin > 7 g/dL

          -  Platelet count > 75,000 cells/mm^3

          -  Absolute neutrophil count > 1000 cells/mm^3

          -  Creatinine < 2.5 mg/dL and creatinine clearance (measured or calculated) >= 60 mL/min

          -  Bilirubin =< 1.5 mg/dL

          -  Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) and
             serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =<
             2.5 times the upper limit of normal

          -  Prior palliative and/or localized radiation therapy is permitted provided at least 4
             weeks have passed from date of last radiation therapy to date of registration;
             patients with prior solitary plasmacytoma treated with radiation therapy with curative
             intent are eligible if the disease has now progressed to active multiple myeloma
             meeting all the eligibility criteria for this protocol

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2

          -  Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
             test with a sensitivity of at least 25 mIU/mL within 10-14 days and again within 24
             hours prior to starting cycle 1 of lenalidomide; further, they must either commit to
             continued abstinence from heterosexual intercourse or begin TWO acceptable methods of
             birth control: one highly effective method (intrauterine device [IUD], birth control
             pills, tubal ligation or partner's vasectomy) and one additional effective method
             (condom, diaphragm or cervical cap); FCBP must also agree to ongoing pregnancy
             testing; men must agree to use a latex condom during sexual contact with a FCBP, even
             if they have had a successful vasectomy starting 4 weeks prior to and while taking
             CC5013 or thalidomide and for four weeks after discontinuing this therapy; a FCBP is a
             sexually mature woman who: has not undergone a hysterectomy or bilateral oophorectomy;
             or has not been naturally postmenopausal for at least 24 consecutive months (i.e., has
             had menses at any time in the preceding 24 consecutive months); all patients must be
             counseled by a trained counselor every 28 days about pregnancy precautions and risks
             of fetal exposure

          -  Patients with a history of prior malignancy are eligible provided there is no active
             malignancy and a low expectation of recurrence within 6 months

        Exclusion Criteria:

          -  No prior systemic therapy with the exception of bisphosphonates for multiple myeloma

          -  Prior glucocorticosteroid therapy for the treatment of multiple myeloma is not
             permitted; prior systemic glucocorticosteroid use for the treatment of non-malignant
             disorders is permitted; concurrent use after registration on the study should be
             restricted to the equivalent of prednisone 10 mg per day; prior or concurrent topical
             or localized glucocorticosteroid therapy to treat non-malignant comorbid disorders is
             permitted

          -  Patients must not have active, uncontrolled seizure disorder; patients must have had
             no seizures in the last 6 months

          -  Patients must not have uncontrolled intercurrent illness including uncontrolled
             hypertension, symptomatic congestive heart failure, unstable angina, uncontrolled
             cardiac arrhythmia, uncontrolled psychiatric illness or social situation that would
             limit compliance with the study, or a prior history of Stevens Johnson syndrome

          -  Patients with smoldering myeloma or monoclonal gammopathy of undetermined significance
             are not eligible

          -  Patients must not have grade 2 or higher peripheral neuropathy due to other medical
             conditions at the time of randomization

          -  Patients must not have active, uncontrolled infection

          -  Patients must not have a history of current or previous deep vein thrombosis or
             pulmonary embolism regardless of whether or not the patient is receiving
             anticoagulation therapy

               -  For patients registered prior to activation of Addendum # 6; patients must be
                  willing and able to take prophylaxis with either aspirin at 325 mg/day or
                  alternative prophylaxis with either low molecular weight heparin or Coumadin

               -  For patients registered after activation of Addendum # 6; patients entering the
                  expansion phase of the protocol, which tests anticoagulant prophylaxis, must be
                  able and willing to be randomized between aspirin at 325 mg/day and Coumadin

          -  Female patients MUST NOT be pregnant or breastfeeding; due to the potential
             teratogenic properties of CC 5013, and the known teratogenicity associated with
             thalidomide, the use of these drugs in this patient population is ABSOLUTELY
             CONTRAINDICATED