Clinical trial NCT00726232: Study to Determine the Safety and Efficacy of INCB018424 in Patients With Polycythemia Vera or Essential Thrombocythemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Myeloproliferative Neoplasm (MPN)
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2008-07-31
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Percentage of Polycythemia Vera Participants With a Confirmed Clinical Partial Response (PR) or Complete Response (CR)
timeFrame: Assessed after 2 cycles (56 days) of treatment on Day 1 of Cycle 3
measure: Percentage of Essential Thrombocythemia (ET) Participants With a Confirmed Clinical Partial Response (PR) or Complete Response (CR)
timeFrame: Assessed after 2 cycles (56 days) of treatment on Day 1 of Cycle 3.
Secondary outcomes:
measure: Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 12 Weeks
timeFrame: Baseline and Week 12 (Cycle 4, Day 1)
measure: Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 24 Weeks
timeFrame: Baseline and Week 24 (Cycle 7, Day 1)
measure: Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 36 Weeks
timeFrame: Baseline and Week 36 (Cycle 10, Day 1)
measure: Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 4 Weeks
timeFrame: Baseline and 4 weeks (Cycle 2, Day 1)
measure: Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 24 Weeks
timeFrame: Baseline and 24 weeks (Cycle 7, Day 1)
measure: Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 36 Weeks
timeFrame: Baseline and 36 weeks (Cycle 10, Day 1)
measure: Change From Baseline to Week 4 in Polycythemia Vera Symptoms
timeFrame: Baseline and Week 4 (Cycle 2, Day 1)
measure: Change From Baseline to Week 4 in Essential Thrombocythemia Symptoms
timeFrame: Baseline and Week 4 (Cycle 2, Day 1)
measure: Change From Baseline to Week 4 in Health-related Quality of Life
timeFrame: Baseline and Week 4 (Cycle 2, Day 1)
Other outcomes:
Locations:
city: Houston
country: United States
state: Texas
city: Bergamo
country: Italy
city: Firenze
country: Italy
city: Pavia
country: Italy
Study officials:
affiliation: Incyte Corporation
name: Albert Assad, MD
role: STUDY_DIRECTOR
References:
citation: Pieri L, Pancrazzi A, Pacilli A, Rabuzzi C, Rotunno G, Fanelli T, Guglielmelli P, Fjerza R, Paoli C, Verstovsek S, Vannucchi AM. JAK2V617F complete molecular remission in polycythemia vera/essential thrombocythemia patients treated with ruxolitinib. Blood. 2015 May 21;125(21):3352-3. doi: 10.1182/blood-2015-01-624536. No abstract available.