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

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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma and Plasma Cell Neoplasm
• Intervention / Treatment: Drug: bortezomib

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 Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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®

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Barbara Ann Karmanos Cancer Institute
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Muneer H. Abidi, MD, Barbara Ann Karmanos Cancer Institute

Study record dates

Study Major Dates

• Study Start: July 1, 2005
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: February 6, 2006
• First Submitted That Met QC Criteria: February 6, 2006
• First Posted (Estimate): February 7, 2006

Study Record Updates

• Last Update Posted (Estimate): November 19, 2013
• Last Update Submitted That Met QC Criteria: November 18, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: stage II multiple myeloma; stage III multiple myeloma; stage I multiple myeloma; refractory multiple myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma; Antineoplastic Agents; Bortezomib
• Other Study ID Numbers: CDR0000455585; P30CA022453 (U.S. NIH Grant/Contract); WSU-D-2957; WSU-0506002467