Phase I/II Randomised Trial of 5-azacitidine Versus 5-azacitidine in Combination With Vorinostat in Patients With Relapsed Acute Myeloid Leukaemia Ineligible for Intensive Chemotherapy
Acute Myeloid Leukaemia (AML) is a common haematological malignancy. As a result of
improvements in myelosuppressive chemotherapy and stem cell transplantation, the outcome of
children and young adults with AML has improved substantially in the past three decades. By
contrast there has only been limited progress in the development of new treatments for older
adults in whom long term survival is less than 20% at present. Therefore there is an urgent
need to develop more effective treatment options for the treatment of AML in older patients,
particularly patients with relapsed disease.
Given the clinical activity of azacitidine monotherapy in de novo AML and its activity in
relapsed disease post-transplant, it is reasonable to propose that this agent may be a
valuable treatment option in older patients with relapsed disease. Phase II trials in AML
also demonstrate increased clinical activity of azacitidine when combined with a histone
deacetylase inhibitor (HDACi), no randomised trials have yet examined this question of
azacitidine monotherapy compared to azacitidine combined with a HDACi.
This will represent the first randomised trial, addressing whether there is a clinical
benefit to be gained from combining treatment of azacitidine with a HDACi in patients with
relapsed AML for whom no effective treatment currently exists.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Phase I - Maximum tolerated dose (MTD) of combination therapy arm
MTD of vorinostat defined as the dose at which only 0 or 1 out of 6 patients experience a dose limiting toxicity (DLT) in either cohort 1 or cohort 2 of Phase I. Patients are expected to have a total of 6 cycles of treatment which is expected to be completed over 6 months. This will be measured for all patients receiving treatment and recruitment is expected to be over a period of 12-18 months.
Upto 6 months
Charles F Craddock, Professor
University of Birmingham
United Kingdom: Medicines and Healthcare Products Regulatory Agency