Phase III Trial of Stem Cell Transplantation Compared to Parenteral Melphalan and Oral Dexamethasone in the Treatment of Primary Systemic Amyloidosis (AL)
- Compare hematologic response rate in patients with primary systemic amyloidosis treated
with conventional chemotherapy comprising low-dose melphalan and dexamethasone vs
high-dose melphalan followed by autologous stem cell transplantation.
- Compare the toxicity of these regimens in these patients.
- Compare the overall and progression-free survival of patients treated with these
- Compare the regression of organ involvement in patients treated with these regimens.
- Compare the duration of response in patients treated with these regimens.
- Correlate clonal burden and time to in vitro amyloid formation with clinical outcomes
in patients treated with these regimens.
- Compare quality of life of patients treated with these regimens.
- Compare the information-seeking behavior in patients treated with these regimens.
OUTLINE: This is a comprehensive cohort study comprising a randomized option and a
nonrandomized option. Patients consenting to randomization are stratified by risk group
(high vs low) and ECOG performance status (0-1 vs 2). They are then randomized to 1 of 2
treatment arms. Patients not consenting to randomization choose their treatment arm.
- Arm I: Patients receive low-dose melphalan IV over 15-30 minutes on day 1 or orally
once daily on days 1-7 and oral dexamethasone on days 1-4 and 22-25. Treatment repeats
every 6 weeks for 10 courses in the absence of disease progression or unacceptable
- Arm II: Patients receive filgrastim (G-CSF) on days -7 to -3 and undergo autologous
hematopoietic stem cell (HSC) collection. Patients receive high-dose melphalan IV over
1 hour on days -2 and -1 and undergo autologous HSC transplantation on day 0.
Blood and bone marrow samples are collected at baseline. Samples are examined by PCR, cDNA,
and nucleotide sequence analysis to determine VH and VL gene families and carrier status.
Urine is collected at baseline and analyzed for light-chain protein levels by exclusion
Quality of life is assessed at baseline, at months 3, 9, and 12, at completion of study
treatment, and then every 6 months for up to 5 years.
After completion of study treatment, patients are followed every 6 months for up to 10
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Hematologic response rate
Morie A. Gertz, MD
United States: Federal Government
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