Bortezomib (Velcade) in Patients With Untreated Multiple Myeloma

This study has been completed.
Sponsor:
Collaborators:
Beth Israel Deaconess Medical Center
Massachusetts General Hospital
Brigham and Women's Hospital
Roswell Park Cancer Institute
Emory University
Memorial Sloan Kettering Cancer Center
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Paul G. Richardson, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00153920
First received: September 8, 2005
Last updated: January 21, 2016
Last verified: January 2016
  Purpose
Bortezomib (Velcade) has just recently been approved by the FDA for the treatment of multiple myeloma in patients who have received at least two prior therapies and have demonstrated disease progression on the last therapy. This study will determine if Velcade is effective in treating patients with multiple myeloma that have had no prior treatment for the disease. We will also use whole-genome scanning to identify drug response biomarkers in bone marrow samples as well as nerve fiber studies to compare nerves prior to the use of Velcade and after treatment with Velcade.

Condition Intervention Phase
Multiple Myeloma
Drug: bortezomib
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: Phase II Trial of Velcade (Bortezomib) in Patients With Previously Untreated Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Objective Response (OR) Rate [ Time Frame: Response was assessed every two cycles on treatment. Treatment duration in months was a median (range) of 5.1 (0.8-6.1). ] [ Designated as safety issue: No ]
    Objective response was defined as complete response (CR) or partial response (PR) according to European Group for Blood and Marrow Transplantation criteria (Blade J et al Br J Haematol 1998). CR required all of the following: Negative immunofixation on the serum and urine at two consecutive times for minimum 6 weeks; Disappearance of soft tissue plasmacytomas for at least 6 weeks; <5% plasma cells in bone marrow on 2 determinations for a minimum of 6 weeks; No increase in the size or number of lytic bone lesions. PR required all the following: ≥50% reduction in the level of the serum monoclonal protein on 2 determinations for minimum 6 weeks; If present, reduction in 24-hour urinary light chain excretion either by ≥90% or to <200 mg on 2 determinations for minimum 6 weeks; ≥50% reduction size of soft tissue plasmacytomas for minimum 6 weeks; No increase in the number or size of lytic bone lesions. Development of a compression fracture does not exclude response in either category.


Secondary Outcome Measures:
  • Very Good Partial Response (VGPR) Rate [ Time Frame: Response was assessed every two cycles on treatment. Treatment duration in months was a median (range) of 5.1 (0.8-6.1). ] [ Designated as safety issue: No ]
    Very good partial response or better was defined per International Uniform Response criteria (Durie B, Harousseau JL, Miquel JS, et al Leukemia 2006). See CR requirements in primary outcome measure plus if serum and urine M protein were unmeasurable then immunoglobulin free light chain (FLC) must be in a normal ratio of 0.26-1.65 at two consecutive times. VGPR required the following: Serum and urine M-component detectable by immunofixation but not on electrophoresis; >=90% reduction in serum M-component plus urine M-component <100 mg per 24 hours (by SPEP and UPEP); if the serum and urine M protein were unmeasurable then a >90% decrease in the difference between involved and uninvolved FLC levels.

  • Time to Progression (TTP) [ Time Frame: Disease was assessed every two cycles on treatment and every 6 weeks in long-term follow-up. Median follow-up was 29 months. ] [ Designated as safety issue: No ]
    TTP based on the Kaplan-Meier method is defined as the time from start of treatment to documentation of disease progression (PD). Participants without evidence of PD were censored at the latest date of last disease assessment or date of initiation of non-protocol therapy. PD was established based European Group for Blood and Marrow Transplantation criteria (Blade J et al Br J Haematol 1998). PD required 1 or more of the following: >25% increase in serum monoclonal protein with absolute minimum of 0.5 g/dL (confirmed on repeat investigation); >25% increase in 24-hour urinary light chain excretion with minimum absolute increase of 200 mg/24 hrs (confirmed on repeat investigation); >25% increase in bone marrow plasma cells with minimum absolute increase of 10%; Definite increase in size of existing or new soft tissue plasmacytomas and/or lytic lesions; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL not attributable to other cause).

  • Progression-Free Survival (PFS) [ Time Frame: Disease was assessed every two cycles on treatment and every 6 weeks in long-term follow-up. Median follow-up was 29 months as of the data analysis. ] [ Designated as safety issue: No ]
    PFS based on the Kaplan-Meier method is defined as the time from study entry to the earliest documentation of disease progression (PD) or death. Participants alive without evidence of PD were censored at the earliest date of last disease assessment or date of initiation of non-protocol therapy. PD was established based European Group for Blood and Marrow Transplantation criteria (Blade J et al Br J Haematol 1998). PD required 1 or more of the following: >25% increase in serum monoclonal protein with absolute minimum of 0.5 g/dL (confirmed on repeat investigation); >25% increase in 24-hour urinary light chain excretion with minimum absolute increase of 200 mg/24 hrs (confirmed on repeat investigation); >25% increase in bone marrow plasma cells with minimum absolute increase of 10%; Definite increase in size of existing soft tissue plasmacytomas and/or lytic lesions or new; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL not attributable to other cause).

  • Any Grade Sensory Neuropathy Events [ Time Frame: Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in months was a median (range) of 5.1 (0.8-6.1). ] [ Designated as safety issue: Yes ]
    Any grade sensory neuropathy events based on CTCAEv3 as reported on case report forms.

  • Any Grade Neuropathic Pain Events [ Time Frame: Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in months was a median (range) of 5.1 (0.8-6.1). ] [ Designated as safety issue: Yes ]
    Any grade neuropathic pain events based on CTCAEv2 as reported on case report forms.


Enrollment: 66
Study Start Date: December 2003
Study Completion Date: September 2008
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: bortezomib
Participants received intravenous bortezomib on a 3-week dosing cycle: 1.3 mg/m2 on days 1, 4, 8 and 11 followed by 10 day rest period for up to 8 cycles or for 2 cycles beyond complete response. Participants with progressive disease or unacceptable toxicity discontinued treatment.
Drug: bortezomib
Other Name: Velcade

Detailed Description:

Primary Objective

• To evaluate the objective response rate (CR + PR) to bortezomib alone in patients with newly diagnosed multiple myeloma.

Secondary Objectives

  • To evaluate the tolerability and toxicity.
  • To evaluate time to progression.
  • To assess the frequency and severity of peripheral neuropathy.
  • To evaluate the impact of early intervention with dose modification and explore symptomatic treatment of peripheral neuropathy.

Exploratory Objectives

• To perform pharmacogenomic analysis of molecular markers associated with response or non-response.

Statistical Design A one stage design is used to evaluate ORR. With 60 evaluable participants, if at least 27 objective responses are observed then bortezomib will be considered promising. The probability of concluding the treatment promising is >0.95 with a true ORR of 55% and <0.07 with a true ORR of 35%.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of multiple myeloma based upon standard criteria
  • Measurable disease, defined as a monoclonal immunoglobulin spike on serum electrophoresis of > 1 g/dl and/or urine monoclonal immunoglobulin spike of > 200mg/24 hours.
  • Karnofsky performance status of > 60
  • Hemoglobin > 8.0 g/dL
  • AST (SGOT) < 3 x ULN
  • ALT < 3 x ULN
  • Total bilirubin < 2 x ULN
  • Is infertile or is practicing an adequate form of contraception
  • 18 years of age or older

Exclusion Criteria:

  • Prior treatment with systemic chemotherapy
  • Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes
  • Plasma cell leukemia
  • Calculated or measured creatinine clearance < 30 mL/minute within 14 days of enrollment
  • Grade 2 or greater peripheral neuropathy
  • Hypersensitivity to bortezomib, boron or mannitol
  • Severe hypercalcemia
  • HIV positive
  • Known active hepatitis B or C
  • New York Hospital Association Class III or IV heart failure
  • Second malignancy requiring concurrent treatment
  • Other serious medical or psychiatric illness
  • Pregnant women
  • Dialysis dependent patients
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00153920

Locations
United States, Georgia
Emory Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 04263
Memorial Sloan-Kettering Cancer Center
New York City, New York, United States, 10021
Sponsors and Collaborators
Dana-Farber Cancer Institute
Beth Israel Deaconess Medical Center
Massachusetts General Hospital
Brigham and Women's Hospital
Roswell Park Cancer Institute
Emory University
Memorial Sloan Kettering Cancer Center
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Paul Richardson, MD Dana-Farber Cancer Institute
  More Information

Publications:
Responsible Party: Paul G. Richardson, MD, Principle Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00153920     History of Changes
Other Study ID Numbers: 03-328 
Study First Received: September 8, 2005
Results First Received: January 21, 2016
Last Updated: January 21, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
multiple myeloma
Velcade
bortezomib

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Bortezomib
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on April 27, 2016