Clinical trial NCT00153920: Bortezomib (Velcade) in Patients With Untreated Multiple Myeloma
Official title: Phase II Trial of Velcade (Bortezomib) in Patients With Previously Untreated Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: multiple myeloma
Velcade
bortezomib
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Beth Israel Deaconess Medical Center
name: Massachusetts General Hospital
name: Brigham and Women's Hospital
name: Roswell Park Cancer Institute
name: Emory University
name: Memorial Sloan Kettering Cancer Center
name: Millennium Pharmaceuticals, Inc.
First posted: 2005-09-12
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Objective Response (OR) Rate
timeFrame: Response was assessed every two cycles on treatment. Treatment duration in months was a median (range) of 5.1 (0.8-6.1).
Secondary outcomes:
measure: Very Good Partial Response (VGPR) Rate
timeFrame: Response was assessed every two cycles on treatment. Treatment duration in months was a median (range) of 5.1 (0.8-6.1).
measure: Time to Progression (TTP)
timeFrame: Disease was assessed every two cycles on treatment and every 6 weeks in long-term follow-up. Median follow-up was 29 months.
measure: Progression-Free Survival (PFS)
timeFrame: 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.
measure: Number of Participants With Treatment-Emergent Sensory Neuropathy
timeFrame: 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).
measure: Number of Participants With Treatment-Emergent Neuropathic Pain
timeFrame: 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).
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory Winship Cancer Institute
state: Georgia
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Paul Richardson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Richardson PG, Xie W, Mitsiades C, Chanan-Khan AA, Lonial S, Hassoun H, Avigan DE, Oaklander AL, Kuter DJ, Wen PY, Kesari S, Briemberg HR, Schlossman RL, Munshi NC, Heffner LT, Doss D, Esseltine DL, Weller E, Anderson KC, Amato AA. Single-agent bortezomib in previously untreated multiple myeloma: efficacy, characterization of peripheral neuropathy, and molecular correlations with response and neuropathy. J Clin Oncol. 2009 Jul 20;27(21):3518-25. doi: 10.1200/JCO.2008.18.3087. Epub 2009 Jun 15.