NCT01617226

Randomised Study of Azacitidine Versus Azacitidine With Vorinostat in Patients With AML or High Risk MDS

Phase II Randomised Trial of 5-azacitidine Versus 5-azacitidine in Combination With Vorinostat in Patients With Acute Myeloid Leukaemia or High Risk Myelodysplastic Syndromes Ineligible for Intensive Chemotherapy

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 260 (actual)
• Sponsor: University of Birmingham · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a multicentre, open-label, randomised phase II trial comparing azacitidine monotherapy with combined azacitidine and vorinostat in patients with newly diagnosed, relapsed or refractory acute myeloid leukaemia or high risk myelodysplastic syndromes ineligible for intensive chemotherapy.

Detailed description

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. There is an urgent need to develop more effective treatment options for the treatment of AML and high risk MDS in older adults. Accumulating evidence suggests that Azacitidine is a potentially important treatment modality in newly diagnosed, relapsed/refractory AML and high risk MDS. Phase II trials in AML and MDS demonstrate increased clinical activity of azacitidine when combined with a HDACi. However no randomised trials have yet examined the important question of whether concurrent HDACi administration increases the clinical activity of Azacitidine. Vorinostat is a new HDACi which shows significant clinical activity in combination with Azacitidine in patients with AML and MDS. We therefore propose a randomised trial of azacitidine compared with azacitidine and vorinostat combination therapy in older adults with newly diagnosed, relapsed, refractory AML or high risk MDS ineligible for intensive chemotherapy. This will represent the first randomised trial, addressing whether there is a clinical benefit to be gained from combining treatment with azacitidine with a HDACi in patients with newly diagnosed, relapsed, refractory AML or high risk MDS for whom limited therapeutic options currently exist.

Conditions

• Leukemia, Myeloid, Acute

Interventions

Type	Name	Description
DRUG	Azacitidine	Azacitidine both arms; 75mg/m\^2 by subcutaneous injection for 7 days of a 28-day cycle for up to 6 cycles.
DRUG	Vorinostat	Vorinostat (with azacitidine) combined therapy arm; 300mg twice daily for 7 days starting on day 3 of each cycle in 28-day cycles for up to 6 cycles.

Timeline

• Start date: 2012-09-01
• Primary completion: 2016-03-01
• Completion: 2020-12-01
• First posted: 2012-06-12
• Last updated: 2021-05-05

Locations

13 sites across 1 country: United Kingdom