NCT00477971

Low-Dose Melphalan and Dexamethasone Compared With High-Dose Melphalan Followed By Autologous Stem Cell Transplant in Treating Patients With Primary Systemic Amyloidosis

Phase III Trial of Stem Cell Transplantation Compared to Parenteral Melphalan and Oral Dexamethasone in the Treatment of Primary Systemic Amyloidosis (AL)

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 89 (actual)
• Sponsor: Mayo Clinic · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Drugs used in chemotherapy, such as melphalan and dexamethasone, work in different ways to stop the growth of plasma cells, either by killing the cells or by stopping them from dividing. Having an autologous stem cell transplant to replace the blood-forming cells destroyed by chemotherapy, allows higher doses of chemotherapy to be given so that more plasma cells are killed. By reducing the number of plasma cells, the disease may progress more slowly. It is not yet known whether combination chemotherapy is more effective than chemotherapy followed by an autologous stem cell transplant in treating primary systemic amyloidosis. PURPOSE: This randomized phase III trial is studying the side effects and how well giving low-dose melphalan together with dexamethasone works compared with high-dose melphalan followed by an autologous stem cell transplant in treating patients with primary systemic amyloidosis.

Detailed description

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.

Conditions

• Multiple Myeloma and Plasma Cell Neoplasm

Interventions

Type	Name	Description
BIOLOGICAL	filgrastim	No administration information given
DRUG	dexamethasone	Given orally
DRUG	melphalan	Given IV or orally
PROCEDURE	autologous hematopoietic stem cell transplantation	Given on day 0

Timeline

• Start date: 2005-10-01
• Primary completion: 2012-07-01
• Completion: 2014-12-01
• First posted: 2007-05-24
• Last updated: 2016-05-17
• Results posted: 2015-07-21

Locations

1 site across 1 country: United States