NCT00789256

Low Dose Melphalan and Bortezomib for AML and High-Risk MDS

A Pilot Study of Low Dose Melphalan and Bortezomib for Treatment of Acute Myelogenous Leukemia and High-Risk Myelodysplastic Syndromes

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 26 (actual)
• Sponsor: Dartmouth-Hitchcock Medical Center · Academic / Other
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

Summary

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).

Detailed description

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.

Conditions

• Acute Myelogenous Leukemia
• Myelodysplastic Syndromes

Interventions

Type	Name	Description
DRUG	Melphalan	Melphalan: 2mg orally, once daily
DRUG	Bortezomib	Bortezomib: 1.0mg/M2 IV on days 1, 4, 8, 11
DRUG	Melphalan and bortezomib

Timeline

• Start date: 2004-09-01
• Primary completion: 2008-12-01
• Completion: 2008-12-01
• First posted: 2008-11-11
• Last updated: 2018-10-24
• Results posted: 2013-07-22

Locations

2 sites across 1 country: United States