Bortezomib, Thalidomide, and Dexamethasone After Melphalan and Stem Cell Transplant in Treating Patients With Stage I-III Multiple Myeloma
Condition: Multiple Myeloma and Plasma Cell Neoplasm; Neurotoxicity
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma; Neurotoxicity Syndromes
Intervention: bortezomib; dexamethasone; melphalan; thalidomide; cytogenetic analysis; fluorescence in situ hybridization; laboratory biomarker analysis; questionnaire administration; autologous hematopoietic stem cell transplantation; peripheral blood stem cell transplantation
Intervention description: Given IV; Given orally; Given IV; Given orally; Performed on baseline and post transplant bone marrow specimens; Performed on baseline and post transplant bone marrow specimens; Baseline, post transplant and prior to start of bortezomib, every 3 months post transplant for the first year, after 6 cycles of bortezomib, every year after transplant for 2-4 years.; Completed at baseline (within 6 weeks prior to enrollment) and at 2 months post transplant and once a month after that for the first year. For the second year the questionnaire will be completed every 3 months as long as on thalidomide for the duration of the study.; Minimum dose of 2 X 10(6) CD34 + cells/kg day 0 after two days of treatment with Melphalan; Minimum dose of 2 X 10(6) CD34 + cells/kg day 0 after two days of treatment with Melphalan
Intervention MeSH terms: Thalidomide; Dexamethasone; Bortezomib; Melphalan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 45.0
Sex: All
Maximum age: 70 Years
Healthy volunteers: No
Keywords: neurotoxicity; stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma

Summary:

      RATIONALE: Bortezomib and thalidomide may stop the growth of multiple myeloma by blocking
      blood flow to the cancer. Bortezomib may also stop the growth of cancer cells by blocking
      some of the enzymes needed for cell growth. Giving bortezomib together with thalidomide and
      dexamethasone may kill any cancer cells that remain after high-dose melphalan and stem cell
      transplant in patients with multiple myeloma.

      PURPOSE: This phase II trial is studying the side effects of giving bortezomib together with
      thalidomide and dexamethasone after melphalan and stem cell transplant and to see how well it
      works in treating patients with stage I-III multiple myeloma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Multiple Myeloma patients with symptomatic disease, stage II or III at diagnosis or
             progressive stage I requiring chemotherapy and/or radiation therapy (by Salmon-Durie
             classification), who are not eligible for tandem transplant study using TMI; because
             of previous radiation or eligibility criteria; documentation of disease staging by
             both Salmon-Durie classification and International Staging System (ISS) is required

          -  Patients with non-secretory myeloma should have measurable serum free-light chain
             protein by the Free-lite test or measurable disease such as a soft tissue myeloma

          -  A minimum of 4 x 10^6 of CD 34 Positive cell/kg has been harvested

          -  A Karnofsky performance status (KPS) of >= 70% is required unless the KPS is impaired
             due to bone disease

          -  No contraindication to the collection of a minimum of 4 x 10^6 CD34+ cells/kg by
             apheresis

          -  All patients must have signed a voluntary, informed consent in accordance with
             institutional and federal guidelines

          -  Bilirubin =< 1.5 mg/dl

          -  Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvate
             transaminase (SGPT) < 2.5 x upper limits of normal

          -  Creatinine clearance of >= 40cc/min

          -  Absolute neutrophil count of > 1000/ul

          -  Platelet count of > 100,000/ul

          -  Cardiac ejection fraction >= 45% by multigated acquisition (MUGA) scan and/or by
             echocardiogram

          -  Diffusing capacity of the lung for carbon monoxide (DLCO) >= 50% of predicted lower
             limit

          -  Human immunodeficiency virus (HIV) antibody tests negative

          -  No other medical, or psychosocial problems which in the opinion of the primary
             physician or principal investigator would place the patient at unacceptably high risk
             from this treatment regimen

        Exclusion Criteria:

          -  Presence of peripheral neuropathy >= grade II

          -  Patients with evidence of disease progression (with >= 25% increase in M protein) on
             bortezomib and or thalidomide therapy prior to transplant

          -  Pregnant or nursing women, as well as women of child bearing age, who are unwilling to
             use a dual method of contraception and men who are unwilling to use condom

          -  Patients with history of hypersensitivity to bortezomib, boron or mannitol