Overview

This trial is active, not recruiting.

Condition leukemia, myeloid, acute
Treatments azacitidine, vorinostat
Phase phase 2
Target HDAC
Sponsor University of Birmingham
Collaborator Leukemia Research Fund
Start date September 2012
End date September 2015
Trial size 260 participants
Trial identifier NCT01617226, RG_11-187

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
azacitidine (75mg/m2) by SC injection on 7 consecutive days (excluding weekends), starting day 1 of 28-day cycles for up to 6 cycles. This should be delivered in a 5-2-2 schedule
azacitidine vidaza, ATC code L01BC07, cas number 320-67-2
Azacitidine both arms; 75mg/m^2 by subcutaneous injection for 7 days of a 28-day cycle for up to 6 cycles.
(Active Comparator)
Patients will receive (75mg/m2) azacitidine by SC injection on 7 consecutive days (excluding weekends), starting day 1 of 28-day cycles for up to 6 cycles. Azacitidine should be delivered in a 5-2-2 schedule. Vorinostat (300mg bid) will be taken orally for 7 consecutive days starting on day 3 of each cycle in 28-day cycles for up to 6 cycles. (Day 3 is defined as the 3rd day of azacitidine administration).
azacitidine vidaza, ATC code L01BC07, cas number 320-67-2
Azacitidine both arms; 75mg/m^2 by subcutaneous injection for 7 days of a 28-day cycle for up to 6 cycles.
vorinostat MK-0683, ATC code L01XX38, cas number 149647-78-9
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.

Primary Outcomes

Measure
Phase II - Overall Response Rate
time frame: Upto 6 months
Phase II - Overall Survival
time frame: Up to 24 months

Secondary Outcomes

Measure
Phase II - Toxicities measured by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
time frame: Up to 28 days
Phase II - Complete Remission (CR) within 6 cycles of treatment
time frame: Up to 6 months
Phase II - Duration of response
time frame: Up to 24 months
Phase II - Dose intensity
time frame: Up to 24 months
Phase II - Quality of Life measured by questionnaires
time frame: Up to 24 months
Phase II - Medical Resource Use
time frame: Up to 24 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Adults with AML (except Acute Promyelocytic Leukaemia (APL)) as defined by the World Health Organisation (WHO) Classification or patients with high risk MDS categorised as INT-2 or high risk according to the International Prognostic Scoring System (IPSS) who are deemed ineligible for intensive chemotherapy on the grounds of age or co-morbidities with ONE of the following disease status:- i) Newly diagnosed OR ii) Relapsed Disease: patients must have achieved a previous morphological CR and show evidence of recurrent disease OR iii) Refractory Disease: patients who have failed to achieve a morphological CR with previous therapy - Patients are able to receive treatment as out-patient - Adequate renal and hepatic function as defined in the Protocol - Patients have given written informed consent - ECOG performance status less than or equal to 2 Exclusion Criteria: - Patients with greater than class III NYHA cardiac impairment - Blastic transformation of Chronic Myeloid Leukaemia - Prior allogeneic/autologous haematopoietic stem cell transplant - Pregnant or lactating women - Adults of reproductive potential not willing to use appropriate, effective, contraception during the trial and for specified amount of time afterwards - Patients who have received prior histone deacetylase inhibitor (HDACi) treatment as anti-tumour therapy. (Patients who have received HDACi treatment for other indications e.g valproic acid for epilepsy may enrol after a 30-day washout period) - Previous anti-tumour therapies, including prior experimental agents or approved anti-tumour small molecules and biologics, within 30 days before the start of protocol treatment. (Patients receiving anti-tumour therapies to control blood counts may enrol into the trial) - Patients who have received prior treatment with demethylating agents such as 5-azacitidine or decitabine - Patients with contraindications to receiving azacitidine or vorinostat such as hypersensitivity, patients unable to have a subcutaneous injection or swallow oral capsules - Active symptomatic fungal, bacterial, and/or viral infection including known active HIV or known viral (A, B, or C) hepatitis - Any co-morbidity that could limit compliance with the trial

Additional Information

Official title 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
Principal investigator Charles F Craddock, Professor
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.
Trial information was received from ClinicalTrials.gov and was last updated in May 2016.
Information provided to ClinicalTrials.gov by University of Birmingham.