S0417 Bortezomib, Thalidomide, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: bortezomib; dexamethasone; thalidomide
Intervention description: induction: 1 mg/m2 IV push days 1, 4, 8, 11 every 21 days; induction: 20 mg/d PO days 1, 2, 4, 5, 8, 9, 11, 12 every 21 days maintenance: 40 mg days 1-4 every 28 days until progression; 100 mg/d PO days 1-21 every 21 days
Intervention MeSH terms: Thalidomide; Dexamethasone; Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma; refractory multiple myeloma

Summary:

      RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes
      needed for cell growth. Biological therapies, such as thalidomide, may stimulate the immune
      system in different ways and stop cancer cells from growing. It may also stop the growth of
      cancer 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 bortezomib together with thalidomide and
      dexamethasone may kill more cancer cells.

      PURPOSE: This phase II trial is studying how well giving bortezomib together with thalidomide
      and dexamethasone works in treating patients with relapsed or refractory multiple myeloma.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosis of multiple myeloma (MM)

               -  Active disease

          -  Relapsed or refractory disease after ≥ 1 prior therapy for MM, that may have included
             autologous or allogeneic stem cell transplantation

               -  Relapse is defined as the occurrence of any of the following during or after
                  prior treatment:

                    -  Myeloma protein level increase by > 100% from the lowest previously recorded
                       level

                    -  Myeloma protein level increase above the defined response criteria for
                       partial remission

                    -  Reappearance of any myeloma peak that had disappeared during the prior
                       treatment

                    -  Increase in the size and number of lytic bone lesions and/or focal lesions
                       by x-ray, MRI, positron emission tomography, and/or CT scan

               -  Refractory disease is defined as no response (i.e., not achieving complete
                  remission, remission, or partial remission) to prior therapy

          -  Measurable disease

          -  No evidence of POEMS (polyneuropathy, organomegaly, endocrinopathy, presence of
             M-protein, and skin changes) syndrome

          -  Must be registered on protocol SWOG-S0334

        PATIENT CHARACTERISTICS:

        Age

          -  18 and over

        Performance status

          -  Zubrod 0-2 (unless due to bone pain)

        Life expectancy

          -  Not specified

        Hematopoietic

          -  Absolute neutrophil count > 1,000/mm^3

          -  Platelet count > 50,000/mm^3

        Hepatic

          -  AST or ALT ≤ 3 times upper limit of normal (ULN)

          -  Bilirubin ≤ 3 times ULN

        Renal

          -  Creatinine clearance > 30 mL/min

        Cardiovascular

          -  No New York Heart Association class III or IV congestive heart failure

          -  No myocardial infarction within the past 6 months

          -  No poorly controlled hypertension

        Other

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile female patients must use effective double method contraception for ≥ 4 weeks
             before, during, and for ≥ 4 weeks after completion of study treatment (during and for
             4 weeks after completion of study treatment for male patients)

          -  No blood, ova, or sperm donation during study treatment

          -  No active infection requiring antibiotics

          -  No neurotoxicity ≥ grade 2

          -  No diabetes mellitus

          -  No other serious medical or psychiatric illness that would preclude study treatment

          -  No other malignancy within the past 3 years except adequately treated basal cell or
             squamous cell skin cancer or carcinoma in situ of the cervix

        PRIOR CONCURRENT THERAPY:

        Biologic therapy

          -  See Disease Characteristics

        Chemotherapy

          -  At least 14 days since prior chemotherapy (28 days for nitrosoureas) and recovered

        Endocrine therapy

          -  Not specified

        Radiotherapy

          -  At least 14 days since prior radiotherapy and recovered

        Surgery

          -  Not specified

        Other

          -  No prior bortezomib alone or combined with thalidomide

          -  Concurrent participation on protocol SWOG-S0309 allowed