Melphalan and Autologous Stem Cell Transplant Followed By Bortezomib and Dexamethasone in Treating Patients With Previously Untreated Systemic Amyloidosis

Multiple Myeloma and Plasma Cell Neoplasm Clinical Trial

Official title: Risk-Adapted Intravenous Melphalan With Stem Cell Transplant and Adjuvant Bortezomib and Dexamethasone for Recently Diagnosed Untreated Patients With Systemic Light-Chain (AL) Amyloidosis

Status Completed

Clinical Trial Summary

RATIONALE: Giving chemotherapy, such as melphalan, before a peripheral stem cell transplant stops the growth of plasma cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as G-CSF, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Bortezomib may stop the growth of plasma cells by blocking some of the enzymes needed for cell growth. Giving bortezomib and dexamethasone after transplant may kill any plasma cells that remain after transplant.

PURPOSE: This phase II trial is studying how well giving melphalan together with an autologous stem cell transplant followed by bortezomib and dexamethasone works in treating patients with previously untreated systemic amyloidosis.

Clinical Trial Description

OBJECTIVES:

Primary

• Determine the response rate in patients with systemic light chain amyloidosis treated with melphalan and autologous stem cell transplantation followed by adjuvant bortezomib and dexamethasone.

Secondary

• 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.

OUTLINE:

• 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 reached.

• 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 CR.

• 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. ;

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Amyloidosis
• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Neoplasms, Plasma Cell
• Plasmacytoma

• NCT number: NCT00458822
• Study type: Interventional
• Source: Memorial Sloan Kettering Cancer Center
• Status: Completed
• Phase: Phase 2
• Start date: February 2007
• Completion date: March 2015