Multiple Myeloma and Plasma Cell Neoplasm
Conditions
Keywords
stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma
Brief summary
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
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.
Interventions
DRUGbortezomib
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
Sponsors
National Cancer Institute (NCI)
Barbara Ann Karmanos Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose | At course 8 |
| Safety and tolerability | At course 8 |
Secondary
| Measure | 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 |
Countries
United States
Outcome results
None listed