A Prospective, Single-Arm, 2-Stage, Open-Label, Phase II Trial of Azacitidine in Relapsed and Refractory Multiple Myeloma.
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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Overall response rate
Andrew Spencer, Assoc. Prof
Australia: Department of Health and Ageing Therapeutic Goods Administration