Transcript Key Exclusion Criteria

Nordic sites
•
Sweden
– Uppsala University Hospital
– PI: Ulla Olsson-Strömberg
> Finland
- Jyväskylä University Hospital
- PI: Dr Marita Nurmi
•
Norway
– Haukeland University Hospital
– PI: Bjørn Tore Gjertsen
> Denmark
- Aarhus Universitetshospital
- PI: Professor Jesper Stentoft
OPTIC - Background
 In PACE, a phase two pivotal trial of ponatinib in heavily pretreated patients with CML or
Ph+ ALL, a starting dose of 45 mg daily was used.
 Longer follow-up in PACE demonstrated a cumulative incidence of vascular events.
 Current data suggest that a dose-side effect relationship exists and that a lower daily
dose may reduce the incidence of vascular events while maintaining a good efficacy.
 OPTIC will test 2 methods for assessing the relationships between exposure, efficacy, and
safety:
1. patients will receive a range of initial doses
2. at defined time points, patients in response will undergo a dose reduction
.
OPTIC study design
Key Inclusion Criteria
> Chronic Phase CML
> Previously treated and resistant to at least 2 TKIs
- Resistance criteria (at least 1 required, mostly according to Baccarani et al, 2009):
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3 months: No cytogenetic response (> 95 % Ph+) or failure to achieve CHR
6 months: Less than a minor cytogenetic response (> 65 % Ph+)
12 months: Less than a PCyR (> 35 % Ph+)
At any time, the development of new BCR-ABL KD mutations in absence of MCyR
At any time, the development of new clonal evolution in absence of MCyR
At any time, the loss of any cytogenetic response (confirmed in at least 2 consecutive
analyses separated by at least 4 weeks)
> Normal QTcF at entry
Key Exclusion Criteria
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Autologous or allogeneic stem cell transplant < 2 months prior to the first dose
Immunosuppressive therapy within 14 days prior to the first dose
Active CNS disease
Clinically significant, uncontrolled, or active cardiovascular disease, including but not
restricted to:
- Any history of MI, unstable angina, cerebrovascular accident or TIA
- Any history of peripheral vascular infarction
- Congestive heart failure (NYHA class III or IV) or left ventricular ejection fraction (LVEF) <
lower limit of normal, within 6 months of enrollment
- History of clinically significant atrial or ventricular arrhythmia
- Venous thromboembolism DVT or pulmonary embolism, within 6 months of enrollment
> Uncontrolled hypertension or poorly controlled diabetes