A dose finding study of Romidepsin and Azacitidine in patients with Acute Myeloid Leukaemia (AML)

• Conditions: Acute myeloid leukaemia (AML); MedDRA version: 14.1Level: PTClassification code 10000880Term: Acute myeloid leukaemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-005023-40-GB
• Lead Sponsor: niversity of Birmingham

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-05-14
• Last Update Posted: 10 June 2013

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

•Adults (aged = 16 years) with newly diagnosed, relapsed or refractory AML (except Acute Promyelocytic Leukaemia (APML) as defined by the WHO classification scheme) •Patients deemed ineligible for conventional chemotherapy on the grounds of age or co-morbidities •Patients able to receive treatment as an out-patient •Patients must have adequate renal and hepatic function as defined below: - Total bilirubin =2.5 x ULN - AST or ALT =2.5 x ULN - eGFR =40mls/min •Patients have given written informed consent •Be willing to comply with the protocol for the duration of the study •ECOG performance status =2
Are the trial subjects under 18? yes
Number of subjects for this age range: 5
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

•Patients with allergies or contraindications to Romidepsin or Azacitidine •Patients with greater than class 3 New York Heart Association (NYHA) cardiac impairment •Blastic transformation of chronic myeloid leukaemia (CML) •Pregnant or lactating women (women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to registration) •Females of childbearing potential (i.e. not post-menopausal or surgically sterilised) who are not willing to use adequate methods of contraception to prevent pregnancy or abstain from heterosexual activity for the duration of the trial and for at least 3 months following treatment discontinuation. This includes females who are not willing to use additional methods of contraception in addition to oestrogen containing contraceptives •Male patients who are not willing to use an adequate method of contraception for the duration of the trial treatment if engaged in sexual activity with a female of childbearing potential and for at least 3 months following treatment discontinuation •Patients with unstable angina, congenital long QT syndrome or a history of myocardial infarction (MI) within the last 6 months •Patients with concurrent active malignancy •Any co-morbidity that could limit compliance with the trial, including but not limited to the following: -Uncontrolled hypertension -Symptomatic congestive heart failure -Uncontrolled cardiac arrhythmia -Psychiatric or social conditions that may interfere with patients compliance -Or any other condition (including laboratory abnormalities) that in the Investigators opinion will affect the patient’s participation in this trial •Patients who have taken any other investigational medicinal product within 4 weeks of study entry •Active symptomatic fungal, bacterial, and/or viral infection including known HIV or known viral (A, B or C) Hepatitis •Patients who are high medical risks due to non-malignant systemic disease as well as those with active uncontrolled infection

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the maximum tolerated dose of Azacitidine in combination with Romidepsin;Secondary Objective: To determine the tolerability and safety of Azacitidine in combination with Romidepsin To determine the major response rate to Azacitidine in combination with Romidepsin;Primary end point(s): Assessment of maximum tolerated dose of Romidepsin when administered in combination with Azacitidine;Timepoint(s) of evaluation of this end point: An analysis of DLT will be performed for each dosing cohort once 3 patients have completed 3 cycles of therapy.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Assessment of tolerability and safety of Azacitidine in combination with Romidepsin. Assessment of response to Azacitidine in combination with Romidepsin.;Timepoint(s) of evaluation of this end point: Tolerability and safety will be assessed using the NCI CTCAE criteria, version 4.0, from commencing treatment until 28 days following treatment discontinuation Response to the combination therapy will be assessed using the Cheson criteria. Major response rate (CR, CRi and PR) will be assessed at the end of cycles 3 and 6 of therapy.