Trial Information

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

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.