E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028537 |
E.1.2 | Term | Myelofibrosis |
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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 identify the MTD of AT9283 in patients with myelofibrosis |
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E.2.2 | Secondary objectives of the trial |
• To characterise the safety and tolerability of AT9283 in patients with myelofibrosis. • To make preliminary observations on the activity of AT9283 in patients with myelofibrosis.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Provision of signed written informed consent. • Age 18 years or older. • Histological evidence of myelofibrosis from a bone marrow biopsy (either primary or following previous treatment of polycythemia vera or essential thrombocythemia). • Patients with intermediate or high risk myelofibrosis (according to Blood Vol 88 No 3 (1996) p1013-1018), who have received prior treatment with at least one therapy which has been discontinued either as a consequence of toxicity or unsatisfactory efficacy. • ECOG performance status 0, 1 or 2. • Negative serum or urine pregnancy test or evidence of surgical sterility or evidence of post-menopausal status. Post-menopausal status is defined as any of the following: natural menopause with menses >1 year ago; radiation induced oophorectomy with last menses >1 year ago; chemotherapy induced menopause with 1 year interval since last menses.
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E.4 | Principal exclusion criteria |
• Be pregnant or lactating (women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to enrolment). Male and female patients of childbearing potential must use appropriate birth control (abstinence, barrier methods, oral contraceptives and/or intrauterine devices) during the entire duration of the study, or the patient must be surgically sterile (with documentation in the patient’s medical records). • Inadequate liver function as demonstrated by serum bilirubin > 2.5 times the upper limits of reference range (ULRR) (unless due to Gilbert’s syndrome) or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or alkaline phosphatase (ALP) ≥ 2.5 times the ULRR. • The presence of a bcr-abl fusion product in bone marrow or peripheral blood. • Significant renal impairment defined as serum creatinine > 1.5 ULRR. • All previous therapies for myelofibrosis must have been completed at least one month prior to treatment with AT9283 (other than supportive therapies such as antibiotics or blood product transfusions). • Prior treatment with a JAK2 inhibitor. • Incomplete recovery from surgery or radiotherapy other than stable < Grade 2 toxicity. • History of an ischemic cardiac event, myocardial infarction or unstable cardiac disease within 3 months of study entry. • Previous malignancy, except for non-basal-cell carcinoma of skin or carcinoma-in-situ of the uterine cervix, unless the tumor was treated with curative intent more than 2 years prior to study entry. • Any evidence of severe or uncontrolled systemic conditions (e.g., systemic infection) or current unstable or uncompensated respiratory or cardiac conditions which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol. • Prior history of infection with human immunodeficiency virus (HIV), known active hepatitis B or C viruses – screening for viral infections is not required for entry to this study. • Epilepsy or other convulsive disorder requiring active management.
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E.5 End points |
E.5.1 | Primary end point(s) |
• The appearance of dose limiting toxicities (DLTs). The MTD will be defined by the number of DLTs during Cycle 1 of treatment only, although decisions on dose escalation will also be dependent upon the occurrence of severe toxicities during repeated cycles of treatment. |
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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 | No |
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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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 |
Dose escalation study in patients |
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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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 5 |
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 | Information not present in EudraCT |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 21 |
E.8.9.1 | In the Member State concerned days | |