Subjects With Previously Untreated Multiple Myeloma Who are Candidates for Autologous Transplantation
Conditions
Interventions
Trade Name: VELCADE
Product Name: VELCADE
Product Code: VELCADE (Bortezomib)
Pharmaceutical Form: Powder for injection*
INN or Proposed INN: VELCADE (bortezomib)
CAS Number: 179324-69-7
Current Sponso
Sponsors
Janssen-Cilag International, N.V.Turnhoutseweg 30, 2340 Beerse, Belgium
Eligibility
Sex/Gender
All
Inclusion criteria
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: – Calcium elevation (>11.5 mg/dL or >2.65 mmol/L) – Renal insufficiency (creatinine >2 mg/dL or >177 umol/L) – Anemia (hemoglobin =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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) 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to determine the overall combined complete response rate (CR rate) (defined in this protocol as the combination of complete response [CR, including sCR and nCR]) following induction treatment with VDT or VDTC in subjects with newly diagnosed symptomatic multiple myeloma who are candidates for HDT/SCT.;Secondary Objective: • To determine the overall combined CR rate, post HDT/SCT, • To determine the: a) overall response rate (CR, VGPR, and PR), b) sCR rate, both pre and post-transplantation, c) time to response, and d) duration of response in each treatment group, • To determine TTP in each treatment group, • To determine the PFS, 1-year survival, and OS in each treatment group, • To evaluate the safety and tolerability of VDT and VDTC, • To determine the time to clinical relapse, • To determine the feasibility of using immunophenotyping of bone marrow aspirates through flow cytometry as a technique to measure the extent of MRD in subjects who have achieved a CR documented by standard techniques such as serum protein electrophoresis (SPEP), urine protein electrophoresis (UPEP), and immunofixation, • To assess subject-reported outcomes (PROs) for each treatment group • To assess medical resource utilization (MRU) related to the disease and the therapy in each treatment group. ;Primary end point(s): The primary endpoint of this study is overall combined complete response rate in the response evaluable population.CR is a valid endpoint for a Phase 2 study designed to determine the optimal induction regime in a subject population with multiple myeloma for whom HDT/SCT has become the standard of care, as it will yield a determination in a reasonable amount of time. Furthermore, post-induction rates of CR/nCR have been demonstrated to be a good surrogate marker for long-term benefit and survival in this subject population.Secondary endpoints (TTP, PFS, and toxicity) were chosen to further confirm the benefit of a 4-d | — |
Countries
Austria, Czech Republic, France, Hungary, Italy, Portugal
Outcome results
None listed