Phase III Trial of Stem Cell Transplantation Compared to Parenteral Melphalan and Oral Dexamethasone in the Treatment of Primary Systemic Amyloidosis (AL)
18 Years
N/A
Both
Multiple Myeloma and Plasma Cell Neoplasm
Trial Information
Phase III Trial of Stem Cell Transplantation Compared to Parenteral Melphalan and Oral Dexamethasone in the Treatment of Primary Systemic Amyloidosis (AL)
OBJECTIVES:
Primary
- 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.
Secondary
- Compare the overall and progression-free survival of patients treated with these
regimens.
- 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
toxicity.
- 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
chromatography.
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
years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed primary systemic amyloidosis
- Amyloid light-chain (AL) disease
- Monoclonal protein by immunoelectrophoresis or immunofixation of the serum or urine
OR abnormal free light-chain ratio
- The following amyloid syndromes* are allowed:
- Amyloid hepatomegaly
- Cardiomyopathy
- Proteinuria
- Peripheral or autonomic neuropathy
- Soft tissue involvement including the tongue, submandibular tissues, and
vascular claudication
- Diffuse interstitial pulmonary AL disease allowed if pulmonary function is
adequate to allow safe transplantation NOTE: *Presence of amyloid deposits in a
plasmacytoma or in bone marrow vessels in an asymptomatic patient does not
constitute an amyloid syndrome
- No secondary or familial amyloidosis
- No multiple myeloma with lytic or destructive bone lesions or myeloma cast
nephropathy
- No multiple myeloma with > 30% plasma cells in the bone marrow
- No amyloidosis manifested only by carpal tunnel syndrome or purpura
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Platelet count ≥ 100,000/mm³
- Bilirubin ≤ 2.0 times upper limit of normal (ULN)
- Alkaline phosphatase ≤ 6 times ULN
- Creatinine ≤ 3.0 mg/dL
- No NYHA class IV heart disease
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No uncontrolled infection
- No HIV positivity
PRIOR CONCURRENT THERAPY:
- Prior alkylating agents, immunosuppressive drugs, or steroids allowed provided they
were given for < 1 month
- Therapeutic steroid doses of ≤ 15 mg per day (or equivalent) allowed at
discretion of physician
- No concurrent participation in another clinical trial involving a pharmacologic agent
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Hematologic response rate
Outcome Time Frame:
10 years
Safety Issue:
No
Principal Investigator
Morie A. Gertz, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Mayo Clinic
Authority:
United States: Federal Government
Study ID:
CDR0000546745
NCT ID:
NCT00477971
Start Date:
October 2005
Completion Date:
December 2014
Related Keywords:
- Multiple Myeloma and Plasma Cell Neoplasm
- primary systemic amyloidosis
- Amyloidosis
- Neoplasms
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
Name | Location |
|---|---|
| Mayo Clinic | Rochester, Minnesota 55905 |
