Velcade (Bortezomib) Consolidation After Transplant (VCAT)
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open-label, Randomised Trial of Bortezomib Consolidation (With Thalidomide and Prednisolone) Vs Thalidomide and Prednisolone Alone in Previously Untreated Subjects With Multiple Myeloma After Receiving Bortezomib, Cyclophosphamide, Dexamethasone (VCD) Induction and Autologous Stem Cell Transplant|
- Consolidation Phase: Percentage of Participants With Complete Response (CR) and Very Good Partial Response (VGPR) at Month 12 [ Time Frame: Month 12 ]CR as per IMWG criteria is defined as negative immunofixation on the serum and urine and disappearance of soft tissue plasmacytomas and less than (<) 5 percent plasma cells in bone marrow. VGPR as per IMWG criteria is defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90 percent or greater reduction in serum M-protein plus urine M-protein level <100 milligram (mg) per 24 hours.
- Consolidation Phase: Pecentage of Participants With Complete Response (CR) at Months 3, 6, 9 and 12 [ Time Frame: Months 3, 6, 9 and 12 ]CR as per IMWG criteria is negative immunofixation on serum and urine and disappearance of soft tissue plasmacytomas and <5 percent plasma cells in bone marrow.
- Consolidation Phase: Percentage of Participants With Stringent Complete Response (sCR) at Months 3, 6, 9 and 12 [ Time Frame: Months 3, 6, 9 and 12 ]sCR as per IMWG criteria is CR plus normal free light chain (FLC) ratio and absence of clonal cells in bone marrow. CR is negative immunofixation on serum and urine and disappearance of soft tissue plasmacytomas and <5 percent plasma cells in bone marrow.
- Consolidation Phase: Progression Free Survival (PFS) [ Time Frame: Baseline until progressive disease (up to 3 years) ]PFS, calculated as the time between randomization to disease progression or death (regardless of cause), whichever occurred first. Progressive disease as per IMWG criteria: increase of >= 25 percent from lowest response level in Serum M-component and/or (the absolute increase must be >=0.5 gram per deciliter [g/dL]) Urine M-component and/or (the absolute increase must be >=200 mg/24 hour. Only in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain levels. The absolute increase must be >10 mg/dL. Bone marrow plasma cell percentage: the absolute percent must be >=10 percent. Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas. Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.65 millimole per liter (mmol/L) that can be attributed solely to the plasma cell proliferative disorder.
- Consolidation Phase: Disease-free Survival (DFS) [ Time Frame: Up to 3 years ]DFS, defined as the duration from the start of CR to the time of relapse from CR. DFS applied only to participants in CR. CR as per IMWG criteria is negative immunofixation on serum and urine and disappearance of soft tissue plasmacytomas and <5 percent plasma cells in bone marrow. Relapse from CR: reappearance of serum or urine M-protein by immunofixation or electrophoresis; development of >= 5 percent plasma cells in the bone marrow; appearance of any other sign of progression (ie, new plasmacytoma, lytic bone lesion, or hypercalcaemia).
- Consolidation Phase: Overall Survival (OS) [ Time Frame: Up to 3 years ]OS was defined as the time between randomization and death. Death of a participant regardless of the cause was considered as an event.
- Consolidation Phase: Change From Baseline in AQOL-6D Scores at the End of the Consolidation Phase [ Time Frame: Month 12 ]The assessment of quality of life-6D (AQoL-6D) is a multi-attribute health-related quality of life instrument (QoL). It comprises dimension scores for independent living, relationships, mental health, coping, pain, senses, and utility score for AQol-6D. Each scale ranges between 1 (best QoL) and -0.04 (worst possible QoL).
- Consolidation Phase: Change From Baseline in FACT/GOG-NTX Total Score at the End of the Consolidation Phase [ Time Frame: Month 12 ]Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX) consists of 10 items and evaluates symptoms and concerns associated specifically with chemotherapy-induced neuropathy. 1 FACT/GOG-NTX total score has a range of 0 to 108 with a higher score indicating better quality of life.
|Study Start Date:||January 2012|
|Estimated Study Completion Date:||January 2018|
|Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Thalidomide consolidation and prednisolone maintenance therapy
Thalidomide: Type=1, unit=mg, number=100, form=tablet, route=oral use. Oral thalidomide consolidation will be administered for a maximum of 12 months or until disease progression along with Prednisolone: Type=1, unit =mg, number=50, form=tablet, route=oral use. Prednisolone maintenance therapy will be administered on alternate days continued indefinitely or until disease progression.
Experimental: Bortezomib + Thalidomide
Bortezomib + Thalidomide consolidation and prednisolone maintenance therapy.
Type=1, unit=mg/ml, number=2.5, form= Solution for injection, route=Subcutaneous use. Bortezomib will be administered as a single subcutaneous injection at a concentration of 1.3 mg/m2 every 2 weeks for 32 weeks (16 doses) in addition to 100 mg daily oral thalidomide consolidation for a maximum of 12 months or until disease progression and 50 mg oral alternate-day prednisolone maintenance continued indefinitely or until disease progression.Drug: Thalidomide
Type=1, unit=mg, number=100, form=tablet, route=oral use. 100 mg daily oral thalidomide consolidation (administered in addition to bortezomib) will be administered for a maximum of 12 months or until disease progression and 50 mg oral alternate-day prednisolone maintenance continued indefinitely or until disease progression.
This is an open-label (patients will know the identity of study treatments), randomized (patients will be assigned by chance to different treatments) study of bortezomib administered as consolidation therapy (therapy given once a remission is achieved) with thalidomide and prednisolone versus thalidomide and prednisolone alone in previously untreated patients with multiple myeloma. Multiple myeloma is a cancer of your plasma cells, a type of white blood cell present in your bone marrow. Patients in this study will receive initial therapy with bortezomib, cyclophosphamide, and dexamethasone (referred to as VCD induction therapy) and will undergo autologous stem cell transplant (ASCT) (a procedure where patients receive an infusion of immature blood cells [stem cells] from their own body to replenish the body's supply of healthy blood-forming cells) before randomization to one of two treatments: Treatment A (thalidomide for up to 12 months or until disease progression and prednisolone on alternate days continued indefinitely or until disease progression) or Treatment B (bortezomib for 32 weeks in addition to thalidomide up to 12 months or until disease progression and prednisolone on alternate days, continued indefinitely or until disease progression.
Throughout the study, the patient's response to therapy will be assessed according to protocol-defined efficacy evaluations and by implementing defined disease response criteria (International Myeloma Working Group [IMWG] criteria). Safety will be evaluated throughout the study. Follow up for progression-free survival (PFS) and overall survival (OS) will be conducted from time of randomization to 3 years post-randomization.
Two interim analyses are planned. The final analysis will be conducted after all patients have completed 12-month consolidation treatment phase or discontinued. The primary endpoint of number and percent of patients with complete response and very good partial response defined by IMWG criteria for multiple myeloma will be examined in the interim and final analyses after approximately 12 months of consolidation therapy. At the completion of the study, updated analyses of PFS and OS will be performed.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01539083
|Woodville South, Australia|
|Korea, Republic of|
|Busan, Korea, Republic of|
|Daegu, Korea, Republic of|
|Hwasun Gun, Korea, Republic of|
|Ulsan, Korea, Republic of|
|Study Director:||Janssen Asia-Pacific Medical Affairs Clinical Trial||Janssen Asia-Pacific Medical Affairs|