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

Sponsor

Barbara Ann Karmanos Cancer Institute (Other)

Overall Status

Completed

CT.gov ID

NCT00288028

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Drug: bortezomib	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jul 1, 2005

Actual Primary Completion Date :

Nov 1, 2010

Actual Study Completion Date :

Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bortezomib 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 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 Other Names: Velcade®

Arm

Intervention/Treatment

Experimental: Bortezomib

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

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

Other Names:

Velcade®

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose [At course 8]
Safety and tolerability [At course 8]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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