Study to Determine the Safety and Efficacy of INCB018424 in Patients With Polycythemia Vera or Essential Thrombocythemia

A Phase 2, Open Label, Dose Regimen Ranging Clinical Study to Determine the Safety and Efficacy of INCB018424 in Patients With Advanced Polycythemia Vera or Essential Thrombocythemia Refractory to Hydroxyurea

To evaluate the safety and efficacy profile of different treatment regimens of Ruxolitinib (INCB018424) administered to two groups of patients; those with polycythemia vera (PV) and those with essential thrombocythemia (ET). Patients in each group were refractory to hydroxyurea or for whom hydroxyurea is contraindicated.

The study consisted of a 2-stage design, which included a dose-ranging phase (during which patients received treatment at their randomized dose) and an expansion phase (after adjustment of dose/regimen to achieve an optimal balance of efficacy and safety). During the dose-ranging phase, patients in each disease group (PV or ET) were randomly assigned in a 1:1:1 ratio independent of each other to receive 1 of 3 treatment regimens with Ruxolitinib, 10 mg twice daily (bid), 25 mg bid, or 50 mg once daily (qd). After patients completed 2 cycles of treatment with Ruxolitinib at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis using their discretion in order to achieve an optimal balance of efficacy and safety. During the expansion phase (ie, after optimization of dose), additional patients with PV or ET were enrolled to receive Ruxolitinib at the dose that was selected upon review of data from the dose-ranging phase. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent.

Inclusion Criteria:

• Confirmed diagnosis of polycythemia vera or essential thrombocythemia as determined by treating physician
• Disease refractory to hydroxyurea or for whom treatment with hydroxyurea is contraindicated or have refused further treatment with hydroxyurea due to side effects.
• Patient meets baseline clinical lab parameters

Exclusion Criteria:

• Treatment with interferon alpha or anagrelide within 7 days and hydroxyurea within 1 day of starting INCB018424.
• Patients diagnosed with another malignancy unless the malignancy was cervical intraepithelial neoplasia or basal or squamous cell skin cancer and the patient has been disease free for > 3 years
• Patients receiving therapy with intermediate or high dose steroids greater than the equivalent of 10 mg prednisone per day
• Clinically significant cardiac disease (New York Heart Association (NYHA) Class III or IV)