Bortezomib, Thalidomide, and Dexamethasone After Melphalan and Stem Cell Transplant in Treating Patients With Stage I-III Multiple Myeloma
Bortezomib, Thalidomide, and Dexamethasone After Melphalan and Stem Cell Transplant in Treating Patients With Stage I-III Multiple Myeloma
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.
OBJECTIVES:

 Primary

 -  To assess the feasibility and toxicities of maintenance therapy with sequential
 bortezomib, thalidomide, and dexamethasone after high-dose melphalan and autologous
 peripheral blood stem cell transplantation in patients with multiple myeloma.

 -  To assess whether administration of sequential bortezomib, thalidomide, and
 dexamethasone can improve progression-free survival of these patients.

 Secondary

 -  To assess whether administration of sequential bortezomib, thalidomide, and
 dexamethasone can increase complete remission rate and duration of response in these
 patients.

 -  To assess the impact of maintenance therapy with sequential bortezomib, thalidomide, and
 dexamethasone after transplantation on overall survival of these patients.

 -  To evaluate the influence of cytogenetic abnormalities (e.g., chromosome 13 deletion, 14
 q32 abnormality, t [4;14], chromosome 1 q21 amplification, and chromosome 17 deletion)
 on outcome by performing conventional cytogenetic study and fluorescence in situ
 hybridization (FISH) studies on baseline and post-transplant bone marrow specimens.

 OUTLINE:

 -  High-dose melphalan and autologous peripheral blood stem cell transplantation (PBSCT):
 Patients receive high-dose melphalan IV over 30 minutes on days -2 and -1 and undergo
 autologous PBSCT on day 0. Patients receive filgrastim (G-CSF) IV or subcutaneously
 beginning on day 5 and continuing until blood counts recover.

 -  Maintenance therapy: Beginning 4-8 weeks after transplantation, patients receive
 bortezomib IV on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the
 absence of disease progression or unacceptable toxicity. Patients also receive oral
 dexamethasone on days 1-4; treatment with dexamethasone repeats every month for 12
 months in the absence of disease progression or unacceptable toxicity. Beginning 2 weeks
 after completion of bortezomib, patients receive oral thalidomide once daily until
 disease progression.

 Patients complete the FACT-GOG neurotoxicity questionnaire periodically. Bone marrow samples
 are collected at baseline and post-transplant for cytogenetic analysis by FISH.
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