Low Dose Melphalan and Bortezomib for AML and High-Risk MDS
The purpose of this study is to determine the response rate of the combination of bortezomib and melphalan in patients with Acute Myelogenous Leukemia (AML) or high-risk Myelodysplastic Syndromes (MDS).
Acute Myelogenous Leukemia
Drug: Melphalan and bortezomib
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Study of Low Dose Melphalan and Bortezomib for Treatment of Acute Myelogenous Leukemia and High-Risk Myelodysplastic Syndromes|
- Determine Response Rate of the Combination of Bortezomib and Melphalan in Patients With AML and High-risk MDS. [ Time Frame: 7 Years ] [ Designated as safety issue: No ]
- Determine Safety Profile of the Combination of Bortezomib and Melphalan. [ Time Frame: 7 Years ] [ Designated as safety issue: Yes ]
- Determine Correlation Between in Vitro and in Vivo Activity of the Combination of Bortezomib and Melphalan. [ Time Frame: 7 Years ] [ Designated as safety issue: No ]
|Study Start Date:||September 2004|
|Study Completion Date:||December 2008|
|Primary Completion Date:||December 2008 (Final data collection date for primary outcome measure)|
Experimental: Study treatment
All patients will receive the following regimen: 1) Melphalan 2 mg orally, once daily. 2) Bortezomib 1.0 mg/M2 IV on days 1, 4, 8, 11.
Melphalan: 2mg orally, once daily
Other Name: VelcadeDrug: Bortezomib
Bortezomib: 1.0mg/M2 IV on days 1, 4, 8, 11Drug: Melphalan and bortezomib
In patients who develop acute myelogenous leukemia (AML) or a high-risk myelodysplastic syndrome (MDS), the current standard treatment involves multidrug induction chemotherapy utilizing an anthracycline or anthraquinone with cytarabine. While chemotherapy has proven effective at inducing remission in up to 90% of patients, elderly patients fair far worse. In patients over the age of sixty, the disease is not only less responsive to therapy, but an increased number of comorbid conditions makes induction therapy a more dangerous endeavor. Because of this, many patients are not offered standard induction chemotherapy and there is a dearth of viable alternatives for treatment of these otherwise fatal diseases.
Low dose melphalan has previously been shown to be an effective palliative treatment for patients diagnosed with AML and high-risk MDS. It was found to have an overall response rate of 40% in AML patients (30% complete remission and 10% partial remission) and a 57% overall response in high-risk MDS patients (33% complete remission, 5% partial remission, and 19% minor responses). This therapy, while not curative, is one of the few options for patients unable to tolerate more intensive treatment regimens, but desiring a potentially effective palliative regimen.
Bortezomib (VELCADE®) is an intravenously administered reversible, selective inhibitor of the 26S proteosome. Although all of the mechanisms by which this novel drug acts as an antineoplastic agent are not fully understood, in vivo and in vitro studies indicate they ultimately result in the inhibition of the gene expression necessary for cell growth and survival pathways, apoptotic pathways, and cellular adhesion, migration, and angiogenesis mechanisms.
Preclinical and clinical evaluation of the combination of melphalan and bortezomib has demonstrated impressive synergy in refractory multiple myeloma cell lines and patients with myeloma. This study aims to determine if these findings hold true in AML and MDS patients.
|United States, Florida|
|Integrated Community Oncology Network|
|Jacksonville, Florida, United States, 32256|
|United States, New Hampshire|
|Dartmouth-Hitchcock Medical Center|
|Lebanon, New Hampshire, United States, 03756|
|Principal Investigator:||Marc Gautier, MD||Dartmouth-Hitchcock Medical Center|
|Principal Investigator:||Jeffrey Bubis, DO||Integrated Community Oncology Network|