Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Antineoplastic Agents

All Drugs and Chemicals

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.

bortezomib

Paul Richardson, MD

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.

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%.

Bortezomib (Velcade) in Patients With Untreated Multiple Myeloma

Phase II Trial of Velcade (Bortezomib) in Patients With Previously Untreated Multiple Myeloma

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.

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.

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).

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).

Number of participants experiencing any grade treatment-emergent sensory neuropathy events based on CTCAEv3 as reported on case report forms.

Number of participants experiencing any grade treatment-emergent neuropathic pain events based on CTCAEv3 as reported on case report forms.

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.

Dana-Farber Cancer Institute

Principle Investigator

Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with bortezomib treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with bortezomib treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.

Age, Continuous

Sex: Female, Male

White

Non-White

Race/Ethnicity, Customized

United States

Region of Enrollment

ISS Stage I

ISS Stage II

ISS Stage III

Unknown

International Staging System (ISS) Stage I: serum ß2-M \< 3.5 mg/L and serum albumin \>/= 3.5 g/dL Stage II: Neither stage I nor stage III Stage III: serum ß2-M \>/= 5.5 mg/L

Spots Global Cancer Trial Database for Bortezomib (Velcade) in Patients With Untreated Multiple Myeloma

Trial Identification

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Interventions

Study Description

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