E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute myeloid leukaemia (AML) |
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E.1.1.1 | Medical condition in easily understood language |
Acute myeloid leukaemia occurs when the bone marrow produces large amounts of immature white blood cells. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10000880 |
E.1.2 | Term | Acute myeloid leukaemia |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the maximum tolerated dose of Azacitidine in combination with Romidepsin |
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E.2.2 | Secondary objectives of the trial |
To determine the tolerability and safety of Azacitidine in combination with Romidepsin To determine the major response rate to Azacitidine in combination with Romidepsin |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
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 |
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E.4 | Principal exclusion criteria |
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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Assessment of maximum tolerated dose of Romidepsin when administered in combination with Azacitidine |
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E.5.1.1 | 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. |
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E.5.2 | Secondary end point(s) |
Assessment of tolerability and safety of Azacitidine in combination with Romidepsin. Assessment of response to Azacitidine in combination with Romidepsin. |
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E.5.2.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
This is the first time that Azacitidine and Romidepsin have been used in combination. |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial will be 6 months after the last data capture. This will allow sufficient time to complete protocol procedures, data collection and data input. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |