Melphalan and Autologous Stem Cell Transplant Followed By Bortezomib and Dexamethasone in Treating Patients With Previously Untreated Systemic Amyloidosis
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.
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
Masking: Open Label, Primary Purpose: Treatment
Conditions
Multiple Myeloma and Plasma Cell Neoplasm
Intervention
bortezomib, dexamethasone
Location
Memorial Sloan-Kettering Cancer Center
New York
New York
United States
10065
Status
Recruiting
Source
National Cancer Institute (NCI)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00458822
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Leukemia, Plasma Cell
A rare, aggressive variant of MULTIPLE MYELOMA characterized by the circulation of excessive PLASMA CELLS in the peripheral blood. It can be a primary manifestation of multiple myeloma or develop as a terminal complication during the disease.
Myeloma Proteins
Abnormal immunoglobulins characteristic of MULTIPLE MYELOMA.
Multiple Myeloma
A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY.
Bence Jones Protein
An abnormal protein with unusual thermosolubility characteristics that is found in the urine of patients with MULTIPLE MYELOMA.
Neoplasms, Second Primary
Abnormal growths of tissue that follow a previous neoplasm but are not metastases of the latter. The second neoplasm may have the same or different histological type and can occur in the same or different organs as the previous neoplasm but in all cases arises from an independent oncogenic event. The development of the second neoplasm may or may not be related to the treatment for the previous neoplasm since genetic risk or predisposing factors may actually be the cause.
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