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

Barbara Ann Karmanos Cancer Institute

Status and phase: Completed; Phase 1

Conditions: Multiple Myeloma and Plasma Cell Neoplasm

Treatments: Drug: bortezomib

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00288028

CDR0000455585

P30CA022453 (U.S. NIH Grant/Contract)

WSU-D-2957

WSU-0506002467

Details and patient eligibility

About

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.

Full 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.

Enrollment: 15 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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15 participants in 1 patient group

Bortezomib

Experimental group

Description:

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.

Treatment:

Drug: bortezomib