Velcade (Bortezomib), Adriamycin Dexamethasone (PAD) or Vincristine Adriamycin Dexamethasone in Second Line Treatment of Multiple Myeloma
The purpose of this research study is to test the safety and effectiveness of replacing vincristine with a drug called bortezomib (also known as "Velcade®"or PS341) in the standard therapy vincristine, doxorubicin (not limited to, but formerly referred to under the tradename Adriamycin) and dexamethasone (VAD) in patients with multiple myeloma. Multiple Myeloma is the second most common cancer of the blood. Bortezomib is the first approved cancer treatment in a new class of medicines called proteasome inhibitors. It disrupts the cell cycle of the cell, affecting numerous biologic pathways, including those related to growth and survival of cancer cells. The treatment will be used as second line treatment, which means either the disease has returned after a period of improvement (relapse) or the disease did not respond to the initial treatment (refractory). Patients will receive either bortezomib (PS341), doxorubicin (Adriamycin) and dexamethasone (PAD) or the VAD standard therapy.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase 2,Multicentre,Randomised,Open-Label,Parallel Group Study to Evaluate Safety & Efficacy of Velcade® When Added to Adriamycin-DexamethasoneTx vs Vincristine-Adriamycin-Dexamethasone Standard Tx in Subj With Multiple Myeloma(MM) Who Are Refractory to or Have Relapsed Post Primary Therapy for MM|
- Safety and efficacy of replacing vincristine with Bortezomib in VAD. Main efficacy criterion is based on best response obtained during treatment.To have a response, the patient should have Complete Response or Partial Response as defined by EBMT criteria [ Time Frame: every 28 days during treatment period for up to 6 to 8 cycles, every one month during 1 year follow up period ] [ Designated as safety issue: No ]
- Secondary objectives are to assess duration of response, event free survival, time to progression, one year survival and overall survival. [ Time Frame: every 28 days during treatment period for up to 6 to 8 cycles, every one month during 1 year follow up period ] [ Designated as safety issue: No ]
|Study Start Date:||October 2006|
|Study Completion Date:||January 2008|
|Primary Completion Date:||January 2008 (Final data collection date for primary outcome measure)|
|Active Comparator: 001||
40 mg daily days 1- 4/9-12/17-20 - cycle 1 // days 1-4/17-20 - subsequent cycleDrug: bortezomib
1.3 mg/m² intravenous (IV) bolus on days 1, 4, 8, and 11Drug: doxorubicin
9mg/m² IV push on days 1 to 4
|Active Comparator: 002||
0.4mg IV push on days 1 to 4Drug: doxorubicin
9mg/m² IV push on days 1 to 4Drug: dexamethasone
40 mg daily days 1- 4/9-12/17-20 - cycle 1 // days 1-4/17-20 - subsequent cycles
Bortezomib, has been approved for use in patients with multiple myeloma, who have already received at least one prior treatment and whose disease is worsening on their last treatment and who have already undergone or are unsuitable for bone marrow transplantation. Bortezomib has significant activity in patients with relapsed multiple myeloma, its efficacy is increased with the addition of dexamethasone and it demonstrates synergy with doxorubicin. The VAD combination has been widely used in multiple myeloma and has demonstrated to be effective in relapsed patients. Based on previous trial results, it is hoped that bortezomib, in replacing vincristine in the VAD standard therapy, can improve the response to treatment of patients with multiple myeloma, with manageable side effects. This is an international, multicentre, randomised, open-label, parallel group study. About 212 patients will take part in the study. Patients will be treated with either bortezomib (PS-341), Adriamycin and Dexamethasone (PAD) or Vincristine, Adriamycin and Dexamethasone (VAD). There will be an initial 14 day screening period to evaluate if the patient is suitable for the study. After screening, eligible patients will be randomised to receive either PAD or VAD. Patients will receive therapy for up to 8 treatment cycles of 28 days each. After the treatment period, there will be a long-term follow-up period with monthly visits until disease progression or relapse. Thereafter follow-up will be continued by at least a phone call every other month. This long-term follow-up period will be performed for all patients until the last patient was treated and followed up for 1 year. Response to treatment will be assessed according to the European group for blood and marrow transplant criteria (EBMT). Disease burden will be monitored by measuring M-protein concentration in serum and in urine every 4 weeks until disease progression or relapse. Thereafter follow-up for survival will be continued every other month by at least a phone call. Safety will be assessed by monitoring of adverse events (AEs), vital signs, physical examination and clinical laboratory tests.
Treatment with PAD or VAD will be for up to 8 cycles of 28 days each. Treatment beyond 6 cycles will be discussed on individual basis. Proposed dosages are: bortezomib 1.3 mg/m² intravenous (IV) bolus on Days 1, 4, 8, and 11; vincristine 0.4mg IV push on Days 1 to 4; doxorubicin 9mg/m² IV push on Days 1 to 4; dexamethasone in 1st cycle 40 mg daily on Days 1 to 4, 9 to 12 and 17 to 20, orally (or equivalent parenteral dose) and on subsequent cycles as 40 mg daily on Days 1 to 4 and 17 to 20 only.