Study of Azacitidine to Treat Relapsed or Refractory Multiple Myeloma
Summary
This is a Phase II trial evaluating the overall response rate, safety and tolerability to azacitidine in patients with relapsed or refractory multiple myeloma.
Description
Multiple myeloma (MM) is an incurable disease with an annual incidence of 14,000 new cases in the US alone. Despite initial sensitivity to corticosteroids, chemotherapy and radiotherapy, relapse is inevitable and there is a median survival of only 2.5 to 3 years. The use of autologous stem cell transplantation (SCT) has improved the duration of disease remission for younger patients but still only results in a median survival of 5 – 6 years.
Since the early 1970s, azacitidine has been investigated for the treatment of acute leukemia. More recently it has been investigated in the treatment of patients with myelodysplastic syndrome (a pre-leukaemic condition). It has been shown to prolong the time to development of acute myeloid leukaemia (AML) or death and has now been approved for use in these patients.
Azacitidine is a cytotoxic drug and is directly toxic to cells, preventing their reproduction or growth. It is also able to cause cells to undergo the process whereby they mature into normal cells. The Myeloma Research Group at The Alfred Hospital has looked at the effect of azacitidine on human myeloma cell lines in the laboratory. Azacitidine was found to prevent both cell growth and causes cell death. In mouse models with multiple myeloma azacitidine prolonged their survival.
The primary aim of this study is to determine the effectiveness of azacitidine in treating patients with multiple myeloma. The other aims of this study are to see whether treating patients with azacitidine extends the time that their myeloma is under control, to determine the number of cycles of azacitidine required to first achieve a response and to determine how safe and tolerable azacitidine is in treating multiple myeloma.
In the first stage a total of 14 people will participate in this project. If in this group of patients azacitidine is shown to be effective as a treatment against multiple myeloma then a further 10 patients will be invited to participate.
Study Design
Allocation: Non-Randomized, Control: Uncontrolled, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Multiple Myeloma
Intervention
Azacitidine
Location
The Alfred Hospital
Melbourne
Victoria
Australia
3004
Status
Recruiting
Source
Bayside Health
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00412919
- 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.
Bence Jones Protein
An abnormal protein with unusual thermosolubility characteristics that is found in the urine of patients with MULTIPLE MYELOMA.
Hla-c Antigens
Class I human histocompatibility (HLA) antigens encoded by a small cluster of structural genes at the C locus on chromosome 6. They have significantly lower immunogenicity than the HLA-A and -B determinants and are therefore of minor importance in donor/recipient crossmatching. Their primary role is their high-risk association with certain disease manifestations (e.g., spondylarthritis, psoriasis, multiple myeloma).
Azacitidine
A pyrimidine analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent.
Clinical Trials
The purpose of this study is to compare the amount of drug that gets into the bloodstream between different tablets taken by mouth and an injection under the skin.
The purpose of this study is to evaluate three things. The first being whether azacitidine is absorbed in the body at the same rate or proportion for different concentrations. The second...
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PubMed Articles
Abstract Multiple myeloma is a common hematological malignancy that urgently requires new approaches to treatment since the disease is not curable using current chemotherapeutic regimens. The aim of t...
Extramedullary Multiple Myeloma.
Abstract Extramedullary disease (EMD), defined as a clonal plasmacytic infiltrate at anatomic sites distant from the bone marrow or adjacent soft tissue in a patient with underlying multiple myeloma,...
Bisphosphonate Therapy in the Treatment of Multiple Myeloma.
Multiple myeloma is an incurable B cell neoplasm caused by the monoclonal expansion of malignant plasma cells in the bone marrow, often resulting in devastating bone disease. For over 2 decades bispho...
Continuous lenalidomide treatment for newly diagnosed multiple myeloma.
Lenalidomide has tumoricidal and immunomodulatory activity against multiple myeloma. This double-blind, multicenter, randomized study compared melphalan-prednisone-lenalidomide induction followed by l...
Bone morphogenetic proteins (BMPs) have been shown to induce apoptosis and growth arrest in myeloma cells. However, the molecular mechanisms behind these events are not known. The MYC oncogene is a ma...
