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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation
ClinicalTrials.gov Identifier:
NCT00726232
First received: July 29, 2008
Last updated: September 5, 2014
Last verified: September 2014
  Purpose

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 will be refractory to hydroxyurea or for whom hydroxyurea is contraindicated.


Condition Intervention Phase
Polycythemia Vera
Essential Thrombocythemia
Drug: Ruxolitinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label Study to Determine the Safety and Efficacy of INCB018424 in Patients With Advanced Polycythemia Vera or Essential Thrombocythemia Refractory to Hydroxyurea

Resource links provided by NLM:


Further study details as provided by Incyte Corporation:

Primary Outcome Measures:
  • Percentage of Polycythemia Vera Participants With a Confirmed Clinical Partial Response (PR) or Complete Response (CR) [ Time Frame: Assessed after 2 cycles (56 days) of treatment on Day 1 of Cycle 3 ] [ Designated as safety issue: Yes ]

    For a confirmed response all criteria must have been sustained for at least 2 months.

    CR:

    • Hematocrit < 45% in men and < 42% in women
    • No phlebotomy for 1 month
    • No palpable splenomegaly
    • White blood cells < 10 x 10^9/L with normal differential and platelets < 400 x 10^9/L
    • No sustained leucopenia or thrombocytopenia (>2 weeks)
    • No systemic PV symptoms (pruritus, night sweats, bone pain, fever, weight loss)

    PR:

    • Hematocrit < 45% in men and < 42% in women
    • 50% reduction in phlebotomy requirements from 6 months before treatment started
    • 50% reduction in palpable splenomegaly

  • Percentage of Essential Thrombocythemia (ET) Participants With a Confirmed Clinical Partial Response (PR) or Complete Response (CR) [ Time Frame: Assessed after 2 cycles (56 days) of treatment on Day 1 of Cycle 3. ] [ Designated as safety issue: Yes ]

    For a confirmed response all criteria must have been sustained for at least 2 months.

    Complete Clinical Response:

    • Platelet count < 400 x 10^9/L
    • White blood cell count < 10 x 10^9/L with normal differential and Hematocrit ≤ upper limit of normal
    • Absence of sustained (> 2 weeks) anemia or leucopenia based on institutional normal ranges
    • Absence of systemic ET symptoms (pruritus, bone pain, weakness, night sweats, paresthesias)
    • Absence of palpable splenomegaly

    Partial Clinical Response:

    • Platelet count < 400 x 10^9/L
    • 50% reduction in palpable splenomegaly


Secondary Outcome Measures:
  • Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 12 Weeks [ Time Frame: Baseline and Week 12 (Cycle 4, Day 1) ] [ Designated as safety issue: No ]

    The individual components of clinical response included:

    • Hematocrit (Hct) < 45% without phlebotomy
    • Absence of palpable splenomegaly
    • 50% reduction in spleen size
    • Platelet count ≤ 400 x 10^9/L
    • White blood cell (WBC) count ≤ 10 x 10^9/L

  • Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 24 Weeks [ Time Frame: Baseline and Week 24 (Cycle 7, Day 1) ] [ Designated as safety issue: No ]

    The individual components of clinical response included:

    • Hematocrit (Hct) < 45% without phlebotomy
    • Absence of palpable splenomegaly
    • 50% reduction in spleen size
    • Platelet count ≤ 400 x 10^9/L
    • White blood cell (WBC) count ≤ 10 x 10^9/L

  • Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 36 Weeks [ Time Frame: Baseline and Week 36 (Cycle 10, Day 1) ] [ Designated as safety issue: No ]

    The individual components of clinical response included:

    • Hematocrit (Hct) < 45% without phlebotomy
    • Absence of palpable splenomegaly
    • 50% reduction in spleen size
    • Platelet count ≤ 400 x 10^9/L
    • White blood cell (WBC) count ≤ 10 x 10^9/L

  • Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 4 Weeks [ Time Frame: Baseline and 4 weeks (Cycle 2, Day 1) ] [ Designated as safety issue: No ]

    The individual components of clinical response included:

    • Platelet count ≤ 400 x 10^9/L
    • White blood cell (WBC) count ≤ 10 x 10^9/L
    • 50% reduction in spleen size
    • Absence of palpable splenomegaly

  • Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 24 Weeks [ Time Frame: Baseline and 24 weeks (Cycle 7, Day 1) ] [ Designated as safety issue: No ]

    The individual components of clinical response included:

    • Platelet count ≤ 400 x 10^9/L
    • White blood cell (WBC) count ≤ 10 x 10^9/L
    • 50% reduction in spleen size
    • Absence of palpable splenomegaly

  • Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 36 Weeks [ Time Frame: Baseline and 36 weeks (Cycle 10, Day 1) ] [ Designated as safety issue: No ]

    The individual components of clinical response included:

    • Platelet count ≤ 400 x 10^9/L
    • White blood cell (WBC) count ≤ 10 x 10^9/L
    • 50% reduction in spleen size
    • Absence of palpable splenomegaly

  • Change From Baseline to Week 4 in Polycythemia Vera Symptoms [ Time Frame: Baseline and Week 4 (Cycle 2, Day 1) ] [ Designated as safety issue: No ]

    Patients were asked to rate their symptoms on a scale of 0 (none) to 10 (worse possible) for the prior week giving the worst level of symptoms experienced during the preceding 7 days. A negative change from baseline score indicates improvement in symptoms.

    For patients with Polycythemia Vera, queried symptoms included fever, itching/pruritus, bone pain and night sweats.


  • Change From Baseline to Week 4 in Essential Thrombocythemia Symptoms [ Time Frame: Baseline and Week 4 (Cycle 2, Day 1) ] [ Designated as safety issue: No ]

    Patients were asked to rate their symptoms on a scale of 0 (none) to 10 (worse possible) for the prior week giving the worst level of symptoms experienced during the preceding 7 days. A negative change from baseline score indicates improvement in symptoms.

    For patients with essential thrombocythemia, queried symptoms included itching/pruritus, bone pain, night sweats, paresthesias (tingling or numbness), and weakness.


  • Change From Baseline to Week 4 in Health-related Quality of Life [ Time Frame: Baseline and Week 4 (Cycle 2, Day 1) ] [ Designated as safety issue: No ]
    Health-related Quality of Life was assessed using the Global Health Status/Quality of Life Scale of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). This scale ranges from 0 to 100, with higher scores indicating higher quality of life.


Enrollment: 73
Study Start Date: July 2008
Estimated Study Completion Date: June 2015
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ruxolitinib 10 mg BID
Participants received 10 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent.
Drug: Ruxolitinib
Ruxolitinib was administered orally and supplied as 5 mg and 25 mg tablets.
Other Name: INCB018424
Experimental: Ruxolitinib 25 mg BID
Participants received 25 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent.
Drug: Ruxolitinib
Ruxolitinib was administered orally and supplied as 5 mg and 25 mg tablets.
Other Name: INCB018424
Experimental: Ruxolitinib 50 mg QD
Participants received 50 mg Ruxolitinib orally once a day (QD) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent.
Drug: Ruxolitinib
Ruxolitinib was administered orally and supplied as 5 mg and 25 mg tablets.
Other Name: INCB018424

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00726232

Locations
United States, Texas
Houston, Texas, United States, 77030
Italy
Bergamo, Italy
Firenze, Italy
Pavia, Italy
Sponsors and Collaborators
Incyte Corporation
Investigators
Study Director: Lance Leopold, MD Incyte Corporation
  More Information

No publications provided

Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT00726232     History of Changes
Other Study ID Numbers: INCB 18424-256
Study First Received: July 29, 2008
Results First Received: January 20, 2012
Last Updated: September 5, 2014
Health Authority: United States: Food and Drug Administration
Italy: Ministry of Health

Additional relevant MeSH terms:
Polycythemia Vera
Thrombocytosis
Thrombocythemia, Essential
Polycythemia
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders

ClinicalTrials.gov processed this record on October 02, 2014