Myelofibrosis MedDRA version: 9.1 Level: LLT Classification code 10028537 Term: Myelofibrosis
Conditions
Interventions
Product Code: AT9283
Pharmaceutical Form: Powder and solvent for solution for infusion
Current Sponsor code: AT9283
Other descriptive name: AT9283 L-lactate salt (AT9283AU)
Concentration unit: mg mill
Sponsors
Astex Therapeutics Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) F.1.3.1 Number of subjects for this age range
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To identify the MTD of AT9283 in patients with myelofibrosis;Secondary Objective: • 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. ;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. | — |
Countries
United Kingdom
Outcome results
None listed