Symptoms and General Pathology

All Conditions

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Blood and Lymph Conditions

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Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

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Myelodysplastic Syndromes

Neoplasms by Histologic Type

Hematologic Diseases

Bone Marrow Diseases

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Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Melphalan

Bortezomib

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

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.

Bortezomib: 1.0mg/M2 IV on days 1, 4, 8, 11

Melphalan and bortezomib

Marc Gautier, MD

Jeffrey Bubis, DO

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).

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.

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

Determine disease response to treatment using Cheson 2000 report of an international working group to standardize response criteria for myelodysplastic syndromes.

The safety profile is based on the number of adverse events experienced by participants as reported in the Adverse Events results section for this protocol.

Leukemic cells will be collected to test the presence of the study drugs using a cell viability assay in vitro and in vivo.

Millennium Pharmaceuticals, Inc.

Dartmouth-Hitchcock Medical Center

Associate Director, Regional Affairs at Norris Cotton Cancer Center

Group 1 will include patients who have not seen prior medical intervention for their disease.

Strata 1

will include patients who have received prior medical intervention for their disease.

Strata 2

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Marc Gautier, MD - Principal Investigator

Response Rate of the Combination of Bortezomib and Melphalan in Patients With AML and High-risk MDS.

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: Melphalan: 2mg orally, once daily

Bortezomib: Bortezomib: 1.0mg/M2 IV on days 1, 4, 8, 11

Melphalan and bortezomib

Study Treatment

Determine Safety Profile of the Combination of Bortezomib and Melphalan.

Includes patients who have not seen prior medical intervention for their disease. Patients assigned to Strata 1 will receive Melphalan 2mg orally, once daily and Bortezomib 1.0 mg/M2 IV on days 1, 4, 8, 11.

Includes patients who have received prior medical intervention for their disease. Patients assigned to Strata 2 will receive Melphalan 2mg orally, once daily and Bortezomib 1.0 mg/M2 IV on days 1, 4, 8, 11.

No data was collected and these results were not obtained. The collaborating laboratory with the capability to perform the assay with leukemic cells was not available to analyze the samples.

Spots Global Cancer Trial Database for melphalan and bortezomib