Bortezomib With Melphalan and Prednisone for Multiple Myeloma (MVP)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00734149
First received: December 26, 2007
Last updated: May 30, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: Bortezomib
Drug: Melphalan
Drug: Prednisone
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective Study of Bortezomib in Combination With Melphalan and Prednisone for Patients With Previously Untreated Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Response [ Time Frame: 6 weeks following completion of treatment ] [ Designated as safety issue: No ]
    Overall response rate equals complete response and partial response per Southwest Oncology Group Criteria. Measurable, quantifiable protein criteria must be present. Acceptable protein criteria are quantitative immunoglobulin IgG, IgA, IgD, IgE or IgM and/or urine M-component (Bence-Jones protein). If both are present, the quantitative immunoglobulin will be followed for response. Complete Remission: The absence of bone marrow or blood findings of multiple myeloma. This includes disappearance of all evidence of serum and urine M-components on electrophoresis as by immunofixation studies. There must also be no evidence of increasing anemia. Partial Remission: A 50-74% reduction in the quantitative immunoglobulin, and if present, a 50-89% reduction in the urine M-component (Bence-Jones protein). Stable/No Remission): A <50% reduction I nthe quantitative immunoglobulin, or if the patient has light-chain disease only, a <50% reduction in the urine M-component (Bence-Jones protein.


Secondary Outcome Measures:
  • Number of Patients With Any Grade or Severe Adverse Event [ Time Frame: At any time during the study and up to 30 days after stopping the study drug ] [ Designated as safety issue: Yes ]
    Number of patients with any grade or severe, defined as ≥ grade 3 by Common Terminology Criteria for Adverse Events (CTCAE) v4.0, adverse events as a measure of safety

  • Median Duration of Response [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
    Duration of response is measured from date of first confirmed response until date of disease progression.


Enrollment: 45
Study Start Date: July 2004
Study Completion Date: February 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Bortezomib
Other Name: Velcade
Drug: Melphalan
Other Name: melphalan
Drug: Prednisone
Other Name: prednisone

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00734149

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Investigators
Principal Investigator: Cristina Gasparetto, MD Duke University
  More Information

Additional Information:
No publications provided

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00734149     History of Changes
Other Study ID Numbers: Pro00008089, 6019
Study First Received: December 26, 2007
Results First Received: February 11, 2013
Last Updated: May 30, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
Multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Melphalan
Bortezomib
Prednisone
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on April 17, 2014