Melphalan, Prednisone, and Thalidomide or Lenalidomide in Treating Patients With Newly Diagnosed Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Laboratory Biomarker Analysis; Lenalidomide; Melphalan; Prednisone; Quality-of-Life Assessment; Thalidomide
Intervention description: Optional correlative studies; Given PO; Given PO; Given PO; Ancillary studies; Given PO
Intervention MeSH terms: Thalidomide; Prednisone; Cortisone; Lenalidomide; Melphalan; Mechlorethamine; Nitrogen Mustard Compounds
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 306.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase III trial studies melphalan and prednisone with thalidomide to see how
      well it works compared to melphalan and prednisone together with lenalidomide in treating
      patients with newly diagnosed multiple myeloma. Drugs used in chemotherapy, such as melphalan
      and prednisone, 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. Thalidomide
      and lenalidomide may stop the growth of multiple myeloma by blocking blood flow to the
      cancer. It is not yet known whether melphalan and prednisone are more effective when given
      together with thalidomide or lenalidomide in treating multiple myeloma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have a confirmed diagnosis of symptomatic myeloma; for the original
             diagnosis of myeloma patients should have met the following criteria at one point in
             their disease course:

               -  Bone marrow plasmacytosis with >= 10% plasma cells or sheets of plasma cells or
                  biopsy proven plasmacytoma

               -  Patient must have had symptomatic disease at initial diagnosis that prompted the
                  initiation of therapy as well as evidence of end-organ damage at the time of
                  diagnosis namely; at least one of the following: anemia, hypercalcemia, bone
                  disease (lytic bone lesions or pathologic fracture), or renal dysfunction

                    -  NOTE: Patients with asymptomatic smoldering myeloma (serum m protein >= 3
                       gm/dL or bone marrow plasma cells >= 10% or greater plus no evidence of
                       anemia, hypercalcemia, lytic bone lesions or renal dysfunction) and
                       monoclonal gammopathy of undetermined significance (serum m protein < 3
                       gm/dL and bone marrow plasma cells < 10% plus no evidence of anemia,
                       hypercalcemia, lytic bone lesions or renal dysfunction) are not eligible

          -  Patients must be > 65 and have declined alternative treatment OR patients who are >=
             18 < 65 are eligible if they:

               -  Are not a candidate for autologous stem cell transplantation in the opinion of
                  the treating physician OR

               -  Have declined transplant or other alternative treatment

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2

          -  All tests below must be performed within 28 days prior to randomization:

               -  Serum free light chain assay

               -  Kappa free light chain

               -  Lambda free light chain

                    -  NOTE: The serum free light chain test is required to be done if the patient
                       does not have measurable disease in the serum or urine; measurable disease
                       in the serum is defined as having a serum M-spike >= 1 g/dL; measurable
                       disease in the urine is defined as having a urine M-spike >= 200 mg/24 hr

                    -  NOTE: urine protein electrophoresis (UPEP) (on a 24 hour collection) is
                       required, no substitute method is acceptable; urine must be followed monthly
                       if the baseline urine M-spike is >= 200 mg/24 hr; 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

          -  Total 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

          -  Patients must be previously untreated for myeloma, although prior treatment for
             myeloma with prednisone or dexamethasone for less than 4 weeks total dosing alone or
             in combination with thalidomide or lenalidomide for less than 2 weeks total dosing is
             allowable

          -  Patients may be receiving bisphosphonates or growth factors (erythropoietin) for
             multiple myeloma; although erythropoietin is allowed, it is strongly discouraged due
             to increased risk of thrombosis when employed alongside thalidomide and/or
             lenalidomide therapy

          -  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

          -  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: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) 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 must not have uncontrolled inter-current illness that would limit compliance
             with the study including:

               -  Uncontrolled hypertension

               -  Symptomatic congestive heart failure

               -  Unstable angina

               -  Uncontrolled cardiac arrhythmia

               -  Uncontrolled psychiatric illness or social situation

               -  Prior history of Stevens Johnson syndrome

          -  Patients must not have grade 2 or higher peripheral neuropathy

          -  Patients must not have an active, uncontrolled infection

          -  Female patients MUST NOT be pregnant or breastfeeding; the use of these drugs in this
             patient population is ABSOLUTELY CONTRAINDICATED; for women of childbearing potential,
             a negative serum pregnancy test is required within 10-14 days prior to randomization;
             for female patients of childbearing potential a negative serum pregnancy test must be
             repeated within 24 hours prior to initiation of treatment, weekly for the first 4
             weeks of treatment and then every 4 weeks if the patient's periods are regular or
             every 2 weeks if they are not; women of childbearing potential must be willing to
             refrain from sexual intercourse or must be willing to employ a dual method of
             contraception, one of which is highly effective [intrauterine device (IUD), birth
             control pills, tubal ligation or partner's vasectomy] and another additional method
             (condom, diaphragm or cervical cap) starting 4 weeks prior to and while taking
             lenalidomide and thalidomide and for four weeks after discontinuing this therapy; the
             male partner of a female using a single form of birth control should use a condom
             regardless of his vasectomy status

          -  Sexually active males must be willing to use a condom (even if they have undergone a
             prior vasectomy) while having intercourse with any woman, while taking lenalidomide
             and thalidomide and for 4 weeks after stopping treatment

          -  Patients must not have had a second active malignancy requiring treatment within the
             last 2 years, with the exceptions of basal or squamous cell carcinoma of the skin, in
             situ carcinoma of the cervix