Phase II Study to Assess the Safety, Efficacy, and Tolerability of Combination Therapy With Velcade (Bortezomib), Doxorubicin, and Dexamethasone (PAD) as Therapy for Patients With Relapsed or Refractory Multiple Myeloma
- To assess the response (partial and complete response) in patients with relapsed or
refractory multiple myeloma receiving bortezomib, doxorubicin hydrochloride, and
dexamethasone (PAD) after prior treatment with a maximum of 6 courses of vincristine,
doxorubicin, and dexamethasone (VAD) or VAD-like regimen.
- To assess the safety and toxicity of PAD therapy in these patients.
- To determine the progression-free survival and overall survival of these patients.
- To compare the original response to VAD with the response obtained with PAD as assessed
by percent fall in paraprotein or Bence Jones Protein, lowest level of abnormal protein
achieved, and duration of response in these patients.
OUTLINE: This is a multicenter study.
STUDY DESIGN & METHODOLOGY:
This is a non-randomised, open labelled phase II trial in patients with relapsed or
refractory multiple myeloma. Patients will be treated with: Bortezomib 1.3mg/m^2 bolus IV
injection days 1, 4, 8 & 11 + Dexamethasone 40mg po on days 1, 2, 3, 4 + Doxorubicin
9mg/m^2/day IV continuous infusion over days 1 - 4. In addition, for the first cycle only,
Dexamethasone will also be given at 40mg po on days 8 - 11 and 15 - 18.
Each treatment regimen will continue for a minimum of four - and up to six - cycles of 21
days (maximum response and 1 cycle).
This study planned to recruit a total of 69 patients in up to 8 centres in Ireland and the
Patients will be enrolled in three groups of 23 patients:
- Relapsed patients, previously treated with VAD or VAD like regimen (VAMP, C-VAMP and
Z-Dex are examples of VAD like therapy) and who have had autologous transplants at
least 1 year previously. Patients may proceed directly to PAD therapy or have had a
maximum of one other line of therapy before PAD.
- Relapsed patients, previously treated with VAD or VAD-like regimen who have not had
autologous transplantation and achieved at least PR (Appendix A). Patients may proceed
directly to PAD therapy or have had a maximum of two other lines of therapy before PAD.
- Patients refractory (MR, NC or PD) to VAD or VAD-like therapy. Patients should proceed
directly to PAD therapy. Patients with NC or PD may proceed to PAD after a minimum of
two cycles of VAD or VAD-like therapy or a minimum of 4 cycles, if MR.
After completion of study treatment, patients are followed every 2 months for 1 year.
Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Response rate (complete and partial response)
Patients will be followed in this study for approximately 16 months after recruitment to cover the period of PAD therapy plus one year follow up. The minimum frequency of reviews will be every two months.
Belfast City Hospital Trust Incorporating Belvoir Park Hospital
Ireland: Irish Medicines Board