Myeloma X Relapse (Intensive): A Phase III Study to Determine the Role of a Second Autologous Stem Cell Transplant as Consolidation Therapy in Patients With Relapsed Multiple Myeloma Following Prior High-dose Chemotherapy and Autologous Stem Cell Rescue.
- To determine the effect on freedom from disease progression in patients with relapsed
multiple myeloma treated with re-induction therapy comprising bortezomib, doxorubicin
hydrochloride, and dexamethasone (PAD) followed by a second autologous stem cell
transplantation (ASCT) with high-dose melphalan vs low-dose cyclophosphamide
- To assess the response rate of PAD in patients following a previous autograft.
- To compare the overall response rate of patients following high-dose melphalan
chemotherapy and autologous stem cell transplantation with low-dose cyclophosphamide
- To assess the overall survival of patients treated with this regimen.
- To assess the safety and toxicity of a second ASCT in these patients.
- To assess the safety and toxicity of PAD in these patients.
- To assess the feasibility of stem cell collection following PAD in these patients.
- To determine the impact of this regimen on pain and quality of life in these patients.
OUTLINE: This is a multicenter study.
- Re-induction (PAD) therapy: Patients receive bortezomib IV on days 1, 4, 8, and 11,
doxorubicin hydrochloride IV continuously on days 1-4, and oral dexamethasone on days
1-4 (and days 8-11 and 15-18 of course 1 only). Treatment repeats every 21 days for up
to 4 courses in the absence of disease progression or unacceptable toxicity.
- Peripheral blood stem cell (PBSC) mobilization and harvest: Within 6-12 weeks, some
patients receive cyclophosphamide IV on day 0 and filgrastim (G-CSF) subcutaneously
(SC) beginning on day 1 and continuing to time of PBSC harvest. PBSCs are then
Patients who successfully complete re-induction therapy and have adequate PBSC mobilization
are stratified according to length of first remission or plateau (≤ vs ≥ 24 months) and
response to PAD re-induction therapy (stable disease vs ≥ partial response). Patients are
randomized to 1 of 2 arms.
- Arm I (high-dose melphalan consolidation therapy): Patients receive high-dose melphalan
IV on day -1 followed by autologous stem cell transplantation (ASCT) on day 0.
- Arm II (low-dose cyclophosphamide consolidation therapy): Patients receive low-dose
cyclophosphamide IV or orally once a week for 12-20 weeks for a total of 12 courses.
Patients complete the EORTC QLQ-C30 and EORTC QLQ-MY20, the Brief Pain Inventory Short Form
(BPI-SF), and the Leeds Assessment of Neuropathic Symptoms and Signs (Self Assessment) Pain
Scale (S-LANSS) questionnaires at baseline and after completion of re-induction therapy.
Patients are followed monthly for up to 100 days after ASCT or at 30 days after low-dose
cyclophosphamide and then every 3 months for 5 years.
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Time to disease progression
Gordon Cook, MD, PhD
Leeds Cancer Centre at St. James's University Hospital