Risk-Adapted Intravenous Melphalan With Stem Cell Transplant and Adjuvant Bortezomib and Dexamethasone for Recently Diagnosed Untreated Patients With Systemic Light-Chain (AL) Amyloidosis
- Determine the response rate in patients with systemic light chain amyloidosis treated
with melphalan and autologous stem cell transplantation followed by adjuvant bortezomib
- Determine the toxicity of this regimen in these patients.
- Assess amyloid disease response to this regimen.
- Determine the progression-free survival of patients treated with this regimen.
- Determine the overall survival of patients treated with this regimen.
- Stem cell mobilization and collection: Patients undergo peripheral blood stem cell
(PBSC) mobilization comprising filgrastim (G-CSF) subcutaneously (SC) for 4-6 days.
PBSC collection continues for 2-3 days until the target number of stem cells is
- Conditioning regimen: One week after PBSC collection, patients receive melphalan IV on
days -3 and -2 and autologous PBSC infusion on day 0. Patients receive G-CSF SC
beginning on day 1 and continuing until blood counts recover.
- Adjuvant therapy: Between 2-3 months after PBSC transplantation, patients are assigned
to 1 of 2 groups.
- Group 1 (patients with plasma cell disease): Patients receive bortezomib IV on
days 1, 4, 8, and 11 and oral dexamethasone once daily on days 1, 2, 4, 5, 8, 9,
11, and 12. Treatment repeats every 3 weeks for 2 courses. Patients then receive
bortezomib on days 1, 8, 15, and 22 and dexamethasone on days 1, 2, 8, 9, 15, 16,
22, and 23. Treatment repeats every 5 weeks for up to 4 courses in the absence of
disease progression or unacceptable toxicity. Patients who achieve complete
response (CR) receive bortezomib and dexamethasone for 2 additional courses after
- Group 2 (patients with plasma cell disease and peripheral neuropathy): Patients
receive oral dexamethasone once daily on days 1-4, 9-12, and 17-20. Treatment
repeats every 30 days for up to 10 courses in the absence of disease progression
or unacceptable toxicity. Patients who achieve CR receive dexamethasone for 2
additional courses after CR.
Patients undergo blood and bone marrow collection and tissue biopsies at baseline and
periodically after completion of study treatment for biomarker correlative studies.
After completion of study treatment, patients are followed every 2 months for 2 year and
then annually thereafter.
PROJECTED ACCRUAL: A total of 45 patients will be accrued for this study.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Response rate at 12 months
Heather Landau, MD
Memorial Sloan-Kettering Cancer Center
United States: Institutional Review Board
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|