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

Primary Purpose

Myeloproliferative Neoplasm (MPN)

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Ruxolitinib
Sponsored by
Incyte Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myeloproliferative Neoplasm (MPN)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Ruxolitinib 10 mg BID

Ruxolitinib 25 mg BID

Ruxolitinib 50 mg QD

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Percentage of Polycythemia Vera Participants With a Confirmed Clinical Partial Response (PR) or Complete Response (CR)
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)
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
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
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
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
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
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
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
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
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
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.

Full Information

First Posted
July 29, 2008
Last Updated
October 24, 2019
Sponsor
Incyte Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT00726232
Brief Title
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

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Terminated
Why Stopped
Termination of the clinical trial by sponsor.
Study Start Date
August 20, 2008 (Actual)
Primary Completion Date
June 20, 2010 (Actual)
Study Completion Date
August 20, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Incyte Corporation

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myeloproliferative Neoplasm (MPN)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
73 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ruxolitinib 10 mg BID
Arm Type
Experimental
Arm Description
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.
Arm Title
Ruxolitinib 25 mg BID
Arm Type
Experimental
Arm Description
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.
Arm Title
Ruxolitinib 50 mg QD
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Ruxolitinib
Other Intervention Name(s)
INCB018424
Intervention Description
Ruxolitinib was administered orally and supplied as 5 mg and 25 mg tablets.
Primary Outcome Measure Information:
Title
Percentage of Polycythemia Vera Participants With a Confirmed Clinical Partial Response (PR) or Complete Response (CR)
Description
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
Time Frame
Assessed after 2 cycles (56 days) of treatment on Day 1 of Cycle 3
Title
Percentage of Essential Thrombocythemia (ET) Participants With a Confirmed Clinical Partial Response (PR) or Complete Response (CR)
Description
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
Time Frame
Assessed after 2 cycles (56 days) of treatment on Day 1 of Cycle 3.
Secondary Outcome Measure Information:
Title
Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 12 Weeks
Description
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
Time Frame
Baseline and Week 12 (Cycle 4, Day 1)
Title
Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 24 Weeks
Description
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
Time Frame
Baseline and Week 24 (Cycle 7, Day 1)
Title
Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 36 Weeks
Description
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
Time Frame
Baseline and Week 36 (Cycle 10, Day 1)
Title
Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 4 Weeks
Description
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
Time Frame
Baseline and 4 weeks (Cycle 2, Day 1)
Title
Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 24 Weeks
Description
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
Time Frame
Baseline and 24 weeks (Cycle 7, Day 1)
Title
Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 36 Weeks
Description
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
Time Frame
Baseline and 36 weeks (Cycle 10, Day 1)
Title
Change From Baseline to Week 4 in Polycythemia Vera Symptoms
Description
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.
Time Frame
Baseline and Week 4 (Cycle 2, Day 1)
Title
Change From Baseline to Week 4 in Essential Thrombocythemia Symptoms
Description
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.
Time Frame
Baseline and Week 4 (Cycle 2, Day 1)
Title
Change From Baseline to Week 4 in Health-related Quality of Life
Description
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.
Time Frame
Baseline and Week 4 (Cycle 2, Day 1)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Albert Assad, MD
Organizational Affiliation
Incyte Corporation
Official's Role
Study Director
Facility Information:
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
City
Bergamo
Country
Italy
City
Firenze
Country
Italy
City
Pavia
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
25999444
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.
Results Reference
derived

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

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