Bortezomib in Treating Patients With Multiple Myeloma Who Have Undergone an Autologous Peripheral Blood Stem Cell Transplant

Study Overview
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Brief Summary
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RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving bortezomib after an autologous peripheral blood stem cell transplant may stop the growth of any cancer cells that remain after transplant. PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib in treating patients with multiple myeloma who have undergone an autologous peripheral blood stem cell transplant.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose (MTD) of bortezomib during maintenance phase after high-dose melphalan and autologous peripheral blood stem cell transplantation in patients with multiple myeloma. Determine the safety and tolerability of bortezomib in these patients. Secondary Determine the overall response rate, complete response rate, and response duration in patients treated with bortezomib at the MTD. OUTLINE: This is an open-label, dose-finding study. Patients receive bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 21 or 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive de-escalating doses of bortezomib (at varying dosing schedules) 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. At least 6 patients are treated at the MTD. After completion of study treatment, patients are followed at 1 year. PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

Official Title
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A Phase I Study of Bortezomib During Maintenance Phase After High Dose Melphalan and Autologous Stem Cell Transplantation in Patients With Multiple Myeloma

Conditions
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Multiple Myeloma and Plasma Cell Neoplasm

Intervention / Treatment
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* Drug: bortezomib


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of multiple myeloma Must have completed high-dose melphalan and autologous peripheral blood stem cell transplantation Transplant must have been completed 30-120 days ago Must not be receiving maintenance therapy Patients must have received 200 mg/m² of melphalan intravenously as a conditioning regimen (no dose reduction allowed) No evidence of amyloidosis No available donor PATIENT CHARACTERISTICS: ECOG performance status (PS) 0-2 or Karnofsky PS 60-100% Absolute neutrophil count > 1,500/mm^3 Platelet count > 75,000/mm^3 Bilirubin ≤ 1.5 times upper limit of normal Transaminase ≤ 3 times upper limit of normal Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Must have a negative HIV test No baseline neurological disease > grade I No cranial nerve palsy No demonstrated resistance to bortezomib No history of allergic reactions attributed to bortezomib, boron, or mannitol No cardiac arrhythmia No unstable angina pectoris No symptomatic congestive heart failure No ongoing or active infection No other uncontrolled illness No psychiatric illness or social situations that would limit compliance with study requirements PRIOR CONCURRENT THERAPY: See Disease Characteristics No other concurrent anticancer therapies or agents No other concurrent investigational agents Not receiving maintenance therapy after prior stem cell transplantation on another clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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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>Bortezomib is administered as a 5 second IV bolus on days 1, 4, 8,11 or 1,8 and 15 of a 21-35 days cycle (Depending on the Dosing schedule). The dosage will be calculated based on actual weight of the patient unless the actual weight is greater than 40% above the ideal body weight. In this instance the dosage will be based on the adjusted ideal body weight. The Adjusted IBW (kg) = IBW + 0.25 x (actual body weight - IBW). The dosage will be adjusted based on the safety and toxicity profile, until a MTD is determined. | Drug: bortezomib<br>* Dose of Bortezomib* Level 1: 1.3 mg/m2 on Day 1, 4, 8, 11 - Every 21 days; Level 2: 1.3 mg/m2 on Day 1, 4, 8, 11 - Every 28 days; Level 3: 1.0 mg/m2 on Day 1, 8, 15 - Every 28 days; Level 4: 1.0 mg/m2 on Day 1, 8, 15 - Every 35 days<br>* Other names: Velcade®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose |  | At course 8 | 
| Safety and tolerability |  | At course 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate by Southwest Oncology Group (SWOG) criteria |  | At day 30 following stem cell transplant and following course 4, course 8, and 1 year of study treatment | 
| Complete response rate by SWOG criteria |  | At day 30 following stem cell transplant and following course 4, course 8, and 1 year of study treatment | 
| Response duration by SWOG criteria |  | At day 30 following stem cell transplant and following course 4, course 8, and 1 year of study treatment | 

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