Bortezomib With Melphalan and Prednisone for Multiple Myeloma

NCT ID: NCT00734149

Last Updated: 2023-11-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-07-31
• Study Completion Date: 2008-02-29

Brief Summary

The purpose of this study is to assess the efficacy of bortezomib in combination with melphalan and prednisone to achieve complete responses for patients with previously untreated multiple myeloma compared to an historical control group. This trial will also evaluate the safety and toxicity of this regimen as well as evaluate the duration of response of this regimen.

Detailed Description

Based on the need to improve front-line therapy for patients less likely to undergo transplant, the promising recent in vitro and clinical work on melphalan and bortezomib, we propose a prospective trial with bortezomib added to standard melphalan and prednisone therapy for previously untreated patients with multiple myeloma. Bortezomib 1.3 mg/m2 will be given twice weekly for two weeks and will be added to standard melphalan and prednisone on a 4-week cycle. This three-drug combination will be compared to historical data. We have treated 2 patients with relapsed disease following >2 prior regimens including high-dose therapy with autologous stem cell support. Each patient received melphalan, prednisone, and bortezomib as described below and both had marked declines in M-protein within 2 cycles. These responses have been sustained for at least 3 months and treatment was well tolerated.

Eligible patients will have histologically confirmed Multiple Myeloma (MM) having not received prior systemic therapy given with the intent to induce remission, be adults, have life expectancy greater than 3 months, adequate performance status, organ and marrow function as described in the protocol, not be pregnant, HIV positive, or taking any investigational agents. Patients must not have history of allergic reactions to study drugs or similar compounds or have uncontrolled intercurrent illness or social situation that would limit compliance with study requirements. Patients must also have the ability to give informed consent.

Study drugs will be administered on an inpatient or outpatient basis. Bortezomib 1.3 mg/m2 is administered intravenously in a 3-5 second bolus on days 1, 4, 8, and 11 of a 28 day cycle. Six cycles are planned. On days when both melphalan and bortezomib are given, melphalan is given at least one hour prior to bortezomib. Melphalan 6 mg/m2 is administered orally on an empty stomach daily on days 1-7 of each cycle. Prednisone 60 mg/m2 is administered orally daily on days 1-7 of each cycle. Supportive care measures such as antiemetics and growth factors may be given.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bortezomib+Melphalan+Prednisone

Bortezomib 1.3 mg/m2 is administered intravenously in a 3-5 second bolus on days 1, 4, 8, and 11 of a 28 day cycle. Six cycles are planned. On days when both melphalan and bortezomib are given, melphalan is given at least one hour prior to bortezomib. Melphalan 6 mg/m2 is administered orally on an empty stomach daily on days 1-7 of each cycle. Prednisone 60 mg/m2 is administered orally daily on days 1-7 of each cycle.

Group Type: EXPERIMENTAL

Bortezomib

Intervention Type: DRUG

Melphalan

Intervention Type: DRUG

Prednisone

Intervention Type: DRUG

Interventions

Bortezomib

Intervention Type: DRUG

Melphalan

Intervention Type: DRUG

Prednisone

Intervention Type: DRUG

Other Intervention Names

Velcade

Eligibility Criteria

Inclusion Criteria

• Patients must have histologically confirmed multiple myeloma, defined as at least one of the following major criteria and one minor criterion or at least three minor criteria:

Major Criteria Minor Criteria Plasmacytoma on tissue biopsy Marrow plasmacytosis 10-29% Marrow plasmacytosis ≥ 30% Monoclonal protein present, less than major criteria Monoclonal protein: Lytic bone lesions

Immunoglobulin G (IgG) > 3.5 g/dl Decrease in uninvolved immunoglobulins:

Immunoglobulin A (IgA) > 2 g/dl Immunoglobulin M (IgM) < 50 mg/dl Bence Jones ≥ 1 g/24 hr IgA < 100 mg/dl IgG < 600 mg/dl

• No prior therapy
• Life expectancy greater than 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status <3 (Karnofsky >40%
• Patients must have normal organ and marrow function. Patients with severe pancytopenia due to myeloma involvement of the bone marrow and patients with renal insufficiency (creatinine > 2 mg/dl) due to myeloma will also be included.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

• Pregnant women
• Patients may not be receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to bortezomib, melphalan, or other agents used in the study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy. Therefore, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with bortezomib or other agents administered during the study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cristina Gasparetto, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Duke University Medical Center

Durham, North Carolina, United States

Countries

United States

Other Identifiers

6019

Identifier Type: OTHER

Identifier Source: secondary_id

Pro00008089

Identifier Type: -

Identifier Source: org_study_id