PAD. ICORG 05-01, V11
- Conditions
- Multiple Myeloma and Plasma Cell Neoplasm
- Interventions
- Registration Number
- NCT00814541
- Lead Sponsor
- Cancer Trials Ireland
- Brief Summary
RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as doxorubicin and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with bortezomib may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving bortezomib together with doxorubicin and dexamethasone works in treating patients with multiple myeloma that has relapsed or not responded to treatment.
PATIENT POPULATION: Patients with relapsed or refractory multiple myeloma requiring therapy will be invited to participate in this study. Eligible patients will be \>18 years old and able to give fully informed consent. Patients must have a Performance Score (PS) of 0-3 (ECOG), measurable serum and/or urine paraprotein, or serum free light chain, bilirubin value of less than one and a half times the upper limit of normal with ALT/AST values less than two and a half times the upper limit of normal. Patients with non-secretory multiple myeloma are excluded from this study.
- Detailed Description
OBJECTIVES:
Primary
* 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.
Secondary
* 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 UK.
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 53
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 2 Dexamethasone 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. 1 Doxorubicin 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. 1 Bortezomib 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. 1 Dexamethasone 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. 2 Doxorubicin 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. 2 Bortezomib 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. 3 Doxorubicin 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. 3 Bortezomib 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. 3 Dexamethasone 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.
- Primary Outcome Measures
Name Time Method 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.
- Secondary Outcome Measures
Name Time Method Progression-free survival 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. Overall survival 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. Compare original response to vincristine, doxorubicin, and dexamethasone with response to bortezomib, doxorubicin hydrochloride, and dexamethasone 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.
Trial Locations
- Locations (8)
Mater Misericordiae University Hospital
🇮🇪Dublin, Ireland
Leeds Cancer Centre at St. James's University Hospital
🇬🇧Leeds, England, United Kingdom
Adelaide and Meath Hospital, Dublin Incorporating the National Children's Hospital
🇮🇪Dublin, Ireland
Mid-Western Cancer Centre at Mid-Western Regional Hospital
🇮🇪Limerick, Ireland
University College Hospital
🇬🇧London, England, United Kingdom
Belfast City Hospital Trust Incorporating Belvoir Park Hospital
🇬🇧Belfast, Northern Ireland, United Kingdom
St. James's Hospital
🇮🇪Dublin, Ireland
Saint Bartholomew's Hospital
🇬🇧London, England, United Kingdom