A Phase 2, Randomized Study of VELCADE® (bortezomib), Dexamethasone, and Thalidomide Versus VELCADE® (bortezomib), Dexamethasone, Thalidomide, and Cyclophosphamide in Subjects With Previously Untreated Multiple Myeloma Who are Candidates for Autologous Transplantation.

• Conditions: Subjects With Previously Untreated Multiple Myeloma Who are Candidates for Autologous Transplantation

• Registration Number: EUCTR2006-006050-10-HU
• Lead Sponsor: Janssen-Cilag International NV, Turnhoutseweg 30, 2340 Beerse, Belgium

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-08-15
• Last Update Posted: 2 December 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 97

Inclusion Criteria

Subjects must satisfy the following criteria before entering the study:
• Male or female between =18 and =70 years
• Subject is a candidate for HDT combined with an autologous SCT
• KPS score of =60%
• Multiple myeloma diagnosed according to the following standard criteria AND requiring systemic therapy:
• Presence of M-component in serum and/or urine, plus clonal plasma cells in the bone marrow and/or a documented clonal plasmacytoma
• PLUS 1 or more of the following, which must be attributable to the underlying plasma cell disorder:
– Calcium elevation (>11.5 mg/dL or >2.8 mmol/L)
– Renal insufficiency (creatinine >2 mg/dL or >177 umol/L)
– Anemia (hemoglobin <10 g/dL [<12.5 mmol/L] or at least 2 g/dL [1.25 mmol/L] below normal)
– Bone disease (lytic lesions or osteopenia)
• AND fulfill criteria for measurable disease, as defined by at least 1 of the following 3 measurements:
– Serum M-protein =1 g/dL (=10 g/L)
– Urine M-protein =200 mg/24 h
– Serum free light chain (FLC) assay: Involved FLC level =10 mg/dL (=100 mg/L) provided serum FLC ratio is abnormal
• Have pretreatment clinical laboratory values meeting the following criteria within 21 days before randomization:
– Platelet count =70 x 109/L
– Hemoglobin =8 g/dL (=4.96 mmol/L) (prior red blood cell [RBC] transfusion or recombinant human erythropoietin use is allowed)
– Absolute neutrophil count (ANC) =1.0 x 109/L
– Aspartate aminotransferase (AST) =2.5 times the upper limit of normal
– Alanine aminotransferase (ALT) =2.5 times the upper limit of normal
– Total bilirubin =1.5 times the upper limit of normal, except in subjects with congenital bilirubinemia, such as Gilbert syndrome
– Serum creatinine =2.5 mg/dL (=220 µmol/L)
– Corrected serum calcium <14 mg/dL (<3.5 mmol/L)
• Women of childbearing potential must agree to use 2 methods of contraception: 1 effective (for example hormonal or tubal ligation) and 1 barrier (for example latex condom, diaphragm) for at least 4 weeks before starting treatment, during the treatment phase, and for 4 weeks after the last dose.
• Males must agree to use barrier contraception (latex condoms) when engaging in reproductive activity during the treatment phase and for 4 weeks after the last dose.
• Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
• To participate in the optional pharmacogenomic component of this study, subjects (or their legally acceptable representative) must have signed the informed consent form for pharmacogenomic research indicating willingness to participate in the pharmacogenomic component of the study (where local regulations permit)]. Refusal to consent for this component does not exclude a subject from participation in the clinical study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Potential subjects who meet any of the following criteria will be excluded from participating in the study:
• Diagnosis of smoldering OR non-secretory multiple myeloma or MGUS. Smoldering multiple myeloma is defined as asymptomatic multiple myeloma with absence of lytic bone lesions. MGUS is defined by presence of serum monoclonal protein <3 g/dL; absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the monoclonal protein; and (if determined) proportion of plasma cells in the
bone marrow of 10% or less.
• Diagnosis of Waldenström’s disease or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions
• Prior or current systemic therapy for multiple myeloma including steroids (with exception of emergency use of a short course [maximum 4 days] of steroids before randomization or of prior or current use of bisphosphonates)
• Radiation therapy and/or plasmapheresis within 15 days before randomization
• History of allergic reaction attributable to compounds being given (VELCADE, thalidomide, dexamethasone, and/or cyclophoshamide) or compounds containing boron or mannitol
• Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0
• Uncontrolled or severe cardiovascular disease, including myocardial infarction, within 6 months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure (see Attachment 3), uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis
• Concurrent medical condition or disease (e.g., active systemic infection, uncontrolled diabetes, pericardial disease, acute diffuse infiltrative pulmonary disease) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study
• Use of any investigational drugs within 30 days before randomization
• Pregnant or lactating women: A serum ß-hCG pregnancy test must be performed at the Screening visit for female subjects of childbearing potential. In the event that a site is unable to obtain the results of a serum pregnancy test in a timely manner, a urine pregnancy test may be substituted. If the test is positive, the subject must be excluded from the study. Confirmation that the subject is not pregnant must be established by a negative serum (or urine) pregnancy test within 24 hours prior to the first dose of study medication. A pregnancy test for naturally post-menopausal women (who have not had menses at any time in the preceding 24 consecutive months) or surgically sterilized women (hysterectomy, bilateral ovariectomy, bilateral salpingectomy) can be conducted at the discretion of the investigator.
• Employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified