Bortezomib, Thalidomide, and Dexamethasone After Melphalan and Stem Cell Transplant 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