E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Haematological Malignancy - Acute Myeloid Leukaemia |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
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 evaluate the activity of azacitidine and vorinostat combined therapy, in terms of overall response (OR) (complete remission (CR), complete remission with incomplete blood count recovery (CRi) and partial remission (PR), as defined by Cheson criteria) and overall survival (OS) in patients with relapsed AML who are ineligible for intensive chemotherapy. |
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E.2.2 | Secondary objectives of the trial |
To determine whether the combination therapy has an acceptable side effect profile, improves quality of life, improves CR rates, and does not significantly increase the supportive care requirements (blood product support/red cell and platelet transfusion requirements/days on antibiotics/days of hospitalisation). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Adults with AML in first relapse (except Acute Promyelocytic Leukaemia (APL) as defined by the World Health Organisation (WHO) Classification) who are deemed ineligible for intensive chemotherapy on the grounds of age or co-morbidities 2)Patients must have achieved a previous morphological CR as defined by Cheson criteria after treatment with conventional myelosuppressive chemotherapy e.g. anthracycline, ara-C, etoposide containing regimens 3)Patients are able to receive treatment as an out-patient 4)Adequate renal and hepatic function 5)Patients have given written informed consent 6)ECOG performance status ≤2 |
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E.4 | Principal exclusion criteria |
1)Patients with greater than class III of the New York Heart Association (NYHA) cardiac impairment 2)Blastic transformation of Chronic Myeloid Leukaemia (CML) 3)Any concurrent active malignancy 4)Prior allogeneic/autologous haematopoietic stem cell transplant (HSCT) 5)Pregnant or lactating women (women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to the start of treatment) 6) Adults of reproductive potential not willing to use appropriate medically approved contraception during the trial and for specified amount of time afterwards. 8)Patients who have received prior HDAC inhibitor-like 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). 9)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 10)Patients who have received prior treatment with demethylating agents such as 5-azacitidine or decitabine 11)Patients with contraindications to receiving azacitidine or vorinostat such as hypersenstivity or patients unable to receive subcutaneous injection 12)Active symptomatic fungal, bacterial, and/or viral infection including known active HIV or known viral (A, B, or C) hepatitis. 13)Any co-morbidity that could limit compliance with the trial |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Overall response rate (CR, CRi, PR), as defined by Cheson criteria and assessed within 6 cycles of treatment. • Overall survival, as defined as the time from date of randomisation to the date of death from any cause. Patients discontinuing study, lost to follow up or still alive at the end of the study will be censored at the date of last follow-up. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Toxicities will be measured and graded according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE) v4) from the date of randomisation until 28 days following treatment discontinuation. • Complete remission within 6 cycles of treatment as defined by Cheson criteria1 • Duration of response, defined as the time from achieving response to the time of relapse • Dose intensity defined as the total dose prescribed to each patient as a proportion of the protocol dose • Quality of Life will be measured using the EORTC QLQ-C30 and EuroQol EQ-5D questionnaire. • Resource use is defined in terms of days in hospital, blood product usage and days on anti-biotics from date of randomisation to 24 months follow up. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 13 |
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 | Yes |
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 trial will be 6 months after the last data capture. . This will allow sufficient time for the completion of protocol procedures, data collection and data input. The Trials Office will notify the MHRA and main REC that the trial has ended and will provide them with a summary of the clinical trial report within 12 months of the end of trial. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |