Lenalidomide and Dexamethasone With or Without Bortezomib in Treating Patients With Previously Untreated 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: Bortezomib; Dexamethasone; Laboratory Biomarker Analysis; Lenalidomide
Intervention description: Given IV; Given PO; Optional correlative studies; Given PO
Intervention MeSH terms: Dexamethasone; Dexamethasone acetate; Lenalidomide; Bortezomib; Ichthammol; BB 1101
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 525.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase III trial studies lenalidomide, dexamethasone, and bortezomib to see
      how well it works compared to dexamethasone and lenalidomide alone in treating patients with
      previously untreated multiple myeloma. Biological therapies, such as lenalidomide, may
      stimulate the immune system in different ways and stop cancer cells from growing. Drugs used
      in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer
      cells, either by killing the cells, by stopping them from dividing, or by stopping them from
      spreading. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes
      needed for cell growth or by blocking blood flow to the cancer. It is not yet known whether
      lenalidomide and dexamethasone is more effective with or without bortezomib in treating
      multiple myeloma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have newly diagnosed multiple myeloma with measurable disease; patients
             with non-secretory multiple myeloma (MM) based upon standard M-component criteria
             (i.e., measurable serum/urine M-component) are not eligible for this study; exception:
             patients with non-secretory MM will be eligible only if the baseline serum Freelite is
             elevated (Note that serum Freelite must be drawn; serum light chains are not
             acceptable); all tests for establishing baseline disease status must be completed
             within 28 days prior to registration and documented on the baseline and follow-up
             tumor assessment form for multiple myeloma

          -  Patients must have received no prior chemotherapy for this disease; patients must have
             received no prior radiotherapy to a large area of the pelvis (more than half of the
             pelvis); prior steroid treatment is allowed provided treatment was not more than 2
             weeks in duration; patients must not have received any prior treatment with bortezomib
             or lenalidomide

          -  Patients must have a Zubrod performance status (PS) of 0 - 3; NOTE: patients with PS 3
             are eligible only if it is documented by the treating physician that the patient's
             multiple myeloma is the central cause of his/her disability; patients who have a PS of
             3 due to other concurrent medical conditions are not eligible for this trial

          -  Platelet count >= 80 x 10^3/mcL; must be obtained within 28 days prior to
             registration; exception: patients with biopsy-proven heavy-marrow involvement, as
             defined by having at least 30% marrow cellularity, with > 50% of the cells being
             malignant plasma cells (documented marrow results required); in this case, although
             there are no required lower limits of normal for the blood counts, the treating
             physician must use his/her medical judgment as to the appropriateness of this study
             therapy for these patients

          -  Absolute neutrophil count (ANC) >= 1 x 10^3/mcL; must be obtained within 28 days prior
             to registration; exception: patients with biopsy-proven heavy-marrow involvement, as
             defined by having at least 30% marrow cellularity, with > 50% of the cells being
             malignant plasma cells (documented marrow results required); in this case, although
             there are no required lower limits of normal for the blood counts, the treating
             physician must use his/her medical judgment as to the appropriateness of this study
             therapy for these patients

          -  Hemoglobin (including patients who have been either transfused or treated with
             erythropoietin [EPO]) >= 9 g/dL; must be obtained within 28 days prior to
             registration; exception: patients with biopsy-proven heavy-marrow involvement, as
             defined by having at least 30% marrow cellularity, with > 50% of the cells being
             malignant plasma cells (documented marrow results required); in this case, although
             there are no required lower limits of normal for the blood counts, the treating
             physician must use his/her medical judgment as to the appropriateness of this study
             therapy for these patients

          -  Patients must be offered participation in the Myeloma Specimen Repository for banking
             and future research; with the patient's consent, bone marrow aspirates and serum
             specimens will be submitted to the Myeloma Specimen Repository for additional testing
             and banking (including SNP testing); patient consent must be obtained before specimens
             may be submitted

          -  Patients must have baseline skeletal survey to include lateral skull,
             anterior-posterior (AP) pelvis and posterior-anterior (PA) chest within 28 days prior
             to registration

          -  Institutions must submit a local cytogenetics report and fluorescence in situ
             hybridization (FISH) analysis report obtained prior to enrollment to S0777; for FISH
             analysis two probes will be utilized: LSI 13 (RBI) 13q14 SpectrumOrange Probe for
             detection of chromosome 13 deletion and LSI p53 (17p13.1) SpectrumOrange probe for
             detection of tumor protein (p)53 locus on chromosome 17; if these exact probes are not
             available locally, it is acceptable to submit results using local protocol; this must
             be noted on the prestudy form; NOTE: it is not required that the results of the FISH
             analysis be known prior to registration, only that pre-registration specimens be drawn
             and sent for analysis prior to registration, and the FISH analysis report be submitted

          -  Patients with pathologic fractures, pneumonia at diagnosis or symptomatic
             hyperviscosity must have these conditions attended to prior to registration (i.e.,
             intramedullary rod, I.V. antibiotics, plasmapheresis)

          -  Patients must have a calculated or measured creatinine clearance > 30 cc/min; measured
             creatinine clearance or serum creatinine used in calculation must be obtained within
             28 days prior to registration

          -  Patients must not have uncontrolled, active infection requiring intravenous
             antibiotics, New York Heart Association (NYHA) class III or class IV heart failure,
             myocardial infarction within the last 6 months, history of treatment for clinically
             significant ventricular cardiac arrhythmias, poorly controlled hypertension, or poorly
             controlled diabetes mellitus; patients must have undergone an electrocardiogram (EKG)
             within 28 days prior to registration

          -  Patients must not have any psychiatric illness that could potentially interfere with
             the completion of treatment according to this protocol

          -  Patients must not be hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
             positive; patients must have a negative hepatitis B and HIV test performed within 28
             days prior to registration; exception: treatment-sensitive HIV infection patients will
             be eligible provided that immunological and virologic indices are indicative of
             favorable long-term survival prospects on the basis of HIV infection, but whose life
             expectancy is limited predominantly by multiple myeloma rather than HIV infection in
             the judgment of the treating physician

          -  Patients must not have a history of cerebral vascular accident with persistent
             neurologic deficits

          -  Patients must be able to take aspirin 325 mg daily (or enoxaparin 40 mg subcutaneously
             [SQ] daily if patient is unable to take aspirin) as prophylactic anticoagulation;
             exception: patients receiving anticoagulation therapy such as Coumadin or heparin will
             NOT receive aspirin, and therefore need not be able to take it

          -  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 and one additional effective method AT THE
             SAME TIME, at least 28 days before starting lenalidomide; 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; 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

          -  No prior malignancy is allowed except for adequately treated basal cell (or squamous
             cell) skin cancer, in situ cervical cancer or other cancer for which the patient has
             been disease-free for five years

          -  Patients must be offered participation in gene expression profiling (GEP) molecular
             studies for the evaluation of genetic polymorphisms

          -  All patients must be informed of the investigational nature of this study and must
             sign and give written consent in accordance with institutional federal guidelines

          -  At the time of patient registration, the treating institution's name and
             identification (ID) number must be provided to the statistical center in order to
             ensure that the current (within 365 days) date of institutional review board approval
             for this study has been entered into the data base