Adjuvant Bortezomib Maintenance Therapy After Autologous Peripheral Stem Cell Transplantation in Treating Patients With Intermediate or Advanced Multiple Myeloma

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Giving bortezomib as maintenance therapy after autologous stem cell transplantation may kill more cancer cells and prolong remission. PURPOSE: This phase I/II trial is studying the side effects and best dose of adjuvant bortezomib as maintenance therapy and to see how well it works in treating patients who have undergone stem cell transplantation for intermediate or advanced multiple myeloma.

Detailed Description
-----------------
OBJECTIVES: Determine response rate, as defined by resolution of bone marrow plasmacytosis and monoclonal paraproteinemia, in the first year after autologous peripheral blood stem cell transplantation in patients with intermediate or advanced multiple myeloma treated with adjuvant bortezomib. Compare progression-free survival of patients treated with adjuvant bortezomib with historical controls treated with autologous transplantation alone. Determine the toxicity of this drug in these patients (phase I). OUTLINE: This is a multicenter, dose-escalation study. Patients receive bortezomib IV on days 1, 8, and 15. Treatment repeats every 28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Patients are followed every 3 months. PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study within 2 years.

Official Title
-----------------
Phase I/II Trial of Autologous Peripheral Blood Progenitor Cell Transplantation With VELCADE Maintenance as Treatment for Intermediate- and Advanced-Stage Multiple Myeloma

Conditions
-----------------
Multiple Myeloma and Plasma Cell Neoplasm

Intervention / Treatment
-----------------
* Drug: bortezomib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of intermediate or advanced multiple myeloma meeting criteria for at least 1 2 following: Intermediate- to high-M-component production rates (immunoglobulin [Ig]G > 5 g/dL or immunoglobulin A (IgA) > 3 g/dL or urine M component > 4 g/24 hours) More than one osteolytic bone lesion or radiographic evidence of diffuse osteoporosis β-2 microglobulin > 3 Nonsecretory myeloma if bone marrow plasmacytosis is greater than 30% Must have undergone autologous peripheral blood stem cell transplantation within the past 3-4 months Age 18 to 69 years old Absolute neutrophil count ≥ 1,000/mm^3 Platelet count ≥ 30,000/mm^3 serum glutamate oxaloacetate transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) ≤ 300 IU Bilirubin ≤ 2 mg/dL Creatinine ≤ 2.0 mg/dL Creatinine clearance ≥ 30 mL/min Negative pregnancy test Fertile patients must use effective contraception Exclusion Criteria: concurrent major cardiac disease that would preclude study participation concurrent major pulmonary disease that would preclude study participation pregnant or nursing peripheral neuropathy ≥ grade 2 history of hypersensitivity to bortezomib, boron, or mannitol concurrent major gastrointestinal or bladder disease that would preclude study participation concurrent major neurologic or psychiatric disease that would preclude study participation dementia or significantly altered mental status that would preclude giving informed consent prior interferon post-transplantation prior thalidomide post-transplantation prior chemotherapy post-transplantation prior radiotherapy post-transplantation prior investigational therapy post-transplantation prior bortezomib prior therapy for myeloma post-transplantation other concurrent anti-myeloma therapy other concurrent investigational therapy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 69 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: bortezomib<br> | Drug: bortezomib<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Disease Progression: The day when bone marrow recurrence and/or new lytic bone marrow lesions on radiograph and/or progressive M-component paraprotein (  25% increase) were detected. Paraprotein progression will be confirmed labs on the consecutive month. | signed consent to progression or end of trial. Up to 5 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | up to 5 years from time of consent | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage II multiple myeloma, stage III multiple myeloma