Myeloproliferative Neoplasm (MPN)
Conditions
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.
Interventions
DRUGRuxolitinib
Ruxolitinib was administered orally and supplied as 5 mg and 25 mg tablets.
Sponsors
Incyte Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Polycythemia Vera Participants With a Confirmed Clinical Partial Response (PR) or Complete Response (CR) | Assessed after 2 cycles (56 days) of treatment on Day 1 of Cycle 3 | 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) | Assessed after 2 cycles (56 days) of treatment on Day 1 of Cycle 3. | 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 36 Weeks | Baseline and Week 36 (Cycle 10, Day 1) | 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 | Baseline and 4 weeks (Cycle 2, Day 1) | 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 | Baseline and 24 weeks (Cycle 7, Day 1) | 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 Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 12 Weeks | Baseline and Week 12 (Cycle 4, Day 1) | 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 |
| Change From Baseline to Week 4 in Polycythemia Vera Symptoms | Baseline and Week 4 (Cycle 2, Day 1) | 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 | Baseline and Week 4 (Cycle 2, Day 1) | 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 | Baseline and Week 4 (Cycle 2, Day 1) | 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. |
| Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 36 Weeks | Baseline and 36 weeks (Cycle 10, Day 1) | 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 Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 24 Weeks | Baseline and Week 24 (Cycle 7, Day 1) | 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 |
Countries
Italy, United States
Participant flow
Recruitment details
This was a multicenter study with 2 sites in the United States and 4 sites in Italy.
Participants by arm
| Arm | Count |
|---|---|
| PV: Ruxolitinib 10 mg BID Participants with Polycythemia Vera 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. | 19 |
| PV: Ruxolitinib 25 mg BID Participants with Polycythemia Vera 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. | 8 |
| PV: Ruxolitinib 50 mg QD Participants with Polycythemia Vera 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. | 7 |
| ET: Ruxolitinib 10 mg BID Participants with Essential Thrombocythemia 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. | 8 |
| ET: Ruxolitinib 25 mg BID Participants with Essential Thrombocythemia 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. | 22 |
| ET: Ruxolitinib 50 mg QD Participants with Essential Thrombocythemia 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. | 9 |
| Total | 73 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Expansion Phase | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 6 | 11 |
| Expansion Phase | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Expansion Phase | Disease progression | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 0 |
| Expansion Phase | Per Investigator: lack of response | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 7 |
| Expansion Phase | Termination of the trial by sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 10 | 16 |
| Expansion Phase | Unspecified reason | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Expansion Phase | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 3 |
| Initial Phase (Dose-finding) | Adverse Event | 2 | 2 | 2 | 1 | 7 | 3 | 0 | 0 |
| Initial Phase (Dose-finding) | Death | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Initial Phase (Dose-finding) | Disease progression | 3 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Initial Phase (Dose-finding) | Per Investigator: lack of response | 1 | 0 | 0 | 2 | 4 | 1 | 0 | 0 |
| Initial Phase (Dose-finding) | Termination of the trial by sponsor | 4 | 3 | 3 | 4 | 9 | 3 | 0 | 0 |
| Initial Phase (Dose-finding) | Unspecified reason | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Initial Phase (Dose-finding) | Withdrawal by Subject | 2 | 0 | 0 | 1 | 0 | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | PV: Ruxolitinib 10 mg BID | Total | ET: Ruxolitinib 50 mg QD | ET: Ruxolitinib 25 mg BID | ET: Ruxolitinib 10 mg BID | PV: Ruxolitinib 50 mg QD | PV: Ruxolitinib 25 mg BID |
|---|---|---|---|---|---|---|---|
| Age, Continuous Essential thrombocythemia group | NA years | 52.9 years STANDARD_DEVIATION 13.19 | 52.8 years STANDARD_DEVIATION 13.48 | 54.1 years STANDARD_DEVIATION 11.55 | 49.6 years STANDARD_DEVIATION 17.89 | NA years | NA years |
| Age, Continuous Polycythemia vera group | 56.3 years STANDARD_DEVIATION 10.98 | 55.4 years STANDARD_DEVIATION 13.2 | NA years | NA years | NA years | 51.0 years STANDARD_DEVIATION 20.49 | 57.0 years STANDARD_DEVIATION 11.26 |
| Age, Customized < 65 | 14 participants | 56 participants | 6 participants | 19 participants | 7 participants | 5 participants | 5 participants |
| Age, Customized >= 65 | 5 participants | 17 participants | 3 participants | 3 participants | 1 participants | 2 participants | 3 participants |
| Hematocrit Hematocrit < 45% | 9 participants | 45 participants | 9 participants | 18 participants | 7 participants | 1 participants | 1 participants |
| Hematocrit Hematocrit ≥ 45% | 10 participants | 28 participants | 0 participants | 4 participants | 1 participants | 6 participants | 7 participants |
| Platelet count < 400 x 10^9 per liter | 6 participants | 12 participants | 0 participants | 0 participants | 1 participants | 1 participants | 4 participants |
| Platelet count ≥400 x 10^9 per liter | 13 participants | 61 participants | 9 participants | 22 participants | 7 participants | 6 participants | 4 participants |
| Sex: Female, Male Female | 11 Participants | 42 Participants | 9 Participants | 13 Participants | 3 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Male | 8 Participants | 31 Participants | 0 Participants | 9 Participants | 5 Participants | 3 Participants | 6 Participants |
| White blood cell count < 10 x 10^9 per liter | 7 participants | 37 participants | 7 participants | 15 participants | 6 participants | 1 participants | 1 participants |
| White blood cell count ≥ 10 x 10^9 per liter | 12 participants | 36 participants | 2 participants | 7 participants | 2 participants | 6 participants | 7 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 19 / 19 | 8 / 8 | 7 / 7 | 8 / 8 | 22 / 22 | 8 / 9 | 34 / 34 | 39 / 39 |
| serious Total, serious adverse events | 2 / 19 | 2 / 8 | 1 / 7 | 1 / 8 | 1 / 22 | 3 / 9 | 17 / 34 | 17 / 39 |
Outcome results
Primary
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
Time frame: Assessed after 2 cycles (56 days) of treatment on Day 1 of Cycle 3.
Population: Essential thrombocythemia intent to treat population, including all patients who took at least 1 dose of study drug. One patient in the 50 mg QD group did not have a response assessment at Cycle 3, Day 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PV: Ruxolitinib 10 mg BID | Percentage of Essential Thrombocythemia (ET) Participants With a Confirmed Clinical Partial Response (PR) or Complete Response (CR) | 13 percentage of participants |
| PV: Ruxolitinib 25 mg BID | Percentage of Essential Thrombocythemia (ET) Participants With a Confirmed Clinical Partial Response (PR) or Complete Response (CR) | 0 percentage of participants |
| PV: Ruxolitinib 50 mg QD | Percentage of Essential Thrombocythemia (ET) Participants With a Confirmed Clinical Partial Response (PR) or Complete Response (CR) | 0 percentage of participants |
Primary
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
Time frame: Assessed after 2 cycles (56 days) of treatment on Day 1 of Cycle 3
Population: Polycythemia Vera intent to treat population, including all patients who took at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PV: Ruxolitinib 10 mg BID | Percentage of Polycythemia Vera Participants With a Confirmed Clinical Partial Response (PR) or Complete Response (CR) | 58 percentage of participants |
| PV: Ruxolitinib 25 mg BID | Percentage of Polycythemia Vera Participants With a Confirmed Clinical Partial Response (PR) or Complete Response (CR) | 50 percentage of participants |
| PV: Ruxolitinib 50 mg QD | Percentage of Polycythemia Vera Participants With a Confirmed Clinical Partial Response (PR) or Complete Response (CR) | 57 percentage of participants |
Secondary
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.
Time frame: Baseline and Week 4 (Cycle 2, Day 1)
Population: Essential Thrombocythemia intent to treat population who had symptom scores \> 0 at baseline and for whom data was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PV: Ruxolitinib 10 mg BID | Change From Baseline to Week 4 in Essential Thrombocythemia Symptoms | Paresthesia | -1.7 score on a scale | Standard Deviation 2.08 |
| PV: Ruxolitinib 10 mg BID | Change From Baseline to Week 4 in Essential Thrombocythemia Symptoms | Itching (pruritus) | -2.7 score on a scale | Standard Deviation 2.89 |
| PV: Ruxolitinib 10 mg BID | Change From Baseline to Week 4 in Essential Thrombocythemia Symptoms | Night Sweats | -5.0 score on a scale | — |
| PV: Ruxolitinib 10 mg BID | Change From Baseline to Week 4 in Essential Thrombocythemia Symptoms | Weakness | -1.0 score on a scale | Standard Deviation 1 |
| PV: Ruxolitinib 10 mg BID | Change From Baseline to Week 4 in Essential Thrombocythemia Symptoms | Bone pain | -3.5 score on a scale | Standard Deviation 2.12 |
| PV: Ruxolitinib 25 mg BID | Change From Baseline to Week 4 in Essential Thrombocythemia Symptoms | Night Sweats | -1.3 score on a scale | Standard Deviation 2.49 |
| PV: Ruxolitinib 25 mg BID | Change From Baseline to Week 4 in Essential Thrombocythemia Symptoms | Weakness | -0.2 score on a scale | Standard Deviation 2.46 |
| PV: Ruxolitinib 25 mg BID | Change From Baseline to Week 4 in Essential Thrombocythemia Symptoms | Paresthesia | -1.6 score on a scale | Standard Deviation 1.5 |
| PV: Ruxolitinib 25 mg BID | Change From Baseline to Week 4 in Essential Thrombocythemia Symptoms | Itching (pruritus) | -1.2 score on a scale | Standard Deviation 2.74 |
| PV: Ruxolitinib 25 mg BID | Change From Baseline to Week 4 in Essential Thrombocythemia Symptoms | Bone pain | -0.4 score on a scale | Standard Deviation 2.26 |
| PV: Ruxolitinib 50 mg QD | Change From Baseline to Week 4 in Essential Thrombocythemia Symptoms | Night Sweats | -4.0 score on a scale | Standard Deviation 4.36 |
| PV: Ruxolitinib 50 mg QD | Change From Baseline to Week 4 in Essential Thrombocythemia Symptoms | Bone pain | -2.3 score on a scale | Standard Deviation 4.93 |
| PV: Ruxolitinib 50 mg QD | Change From Baseline to Week 4 in Essential Thrombocythemia Symptoms | Paresthesia | -2.8 score on a scale | Standard Deviation 2.93 |
| PV: Ruxolitinib 50 mg QD | Change From Baseline to Week 4 in Essential Thrombocythemia Symptoms | Weakness | -1.7 score on a scale | Standard Deviation 2.52 |
Secondary
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.
Time frame: Baseline and Week 4 (Cycle 2, Day 1)
Population: Intent to treat population. The intent-to-treat (ITT) population included all subjects who took at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PV: Ruxolitinib 10 mg BID | Change From Baseline to Week 4 in Health-related Quality of Life | 10.9 units on a scale | Standard Deviation 10.8 |
| PV: Ruxolitinib 25 mg BID | Change From Baseline to Week 4 in Health-related Quality of Life | 6.3 units on a scale | Standard Deviation 14 |
| PV: Ruxolitinib 50 mg QD | Change From Baseline to Week 4 in Health-related Quality of Life | 14.6 units on a scale | Standard Deviation 17.78 |
| ET: Ruxolitinib 10 mg BID | Change From Baseline to Week 4 in Health-related Quality of Life | -2.1 units on a scale | Standard Deviation 10.5 |
| ET: Ruxolitinib 25 mg BID | Change From Baseline to Week 4 in Health-related Quality of Life | 3.0 units on a scale | Standard Deviation 27.6 |
| ET: Ruxolitinib 50 mg QD | Change From Baseline to Week 4 in Health-related Quality of Life | 11.2 units on a scale | Standard Deviation 23.4 |
Secondary
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.
Time frame: Baseline and Week 4 (Cycle 2, Day 1)
Population: Polycythemia Vera intent to treat population who had symptom scores \> 0 at baseline for whom data was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PV: Ruxolitinib 10 mg BID | Change From Baseline to Week 4 in Polycythemia Vera Symptoms | Itching (pruritus) | -4.2 scores on a scale | Standard Deviation 3.63 |
| PV: Ruxolitinib 10 mg BID | Change From Baseline to Week 4 in Polycythemia Vera Symptoms | Fever | -2.0 scores on a scale | Standard Deviation 1.41 |
| PV: Ruxolitinib 10 mg BID | Change From Baseline to Week 4 in Polycythemia Vera Symptoms | Bone pain | -2.0 scores on a scale | Standard Deviation 1.95 |
| PV: Ruxolitinib 10 mg BID | Change From Baseline to Week 4 in Polycythemia Vera Symptoms | Night sweats | -1.9 scores on a scale | Standard Deviation 2.52 |
| PV: Ruxolitinib 25 mg BID | Change From Baseline to Week 4 in Polycythemia Vera Symptoms | Itching (pruritus) | -4.6 scores on a scale | Standard Deviation 1.85 |
| PV: Ruxolitinib 25 mg BID | Change From Baseline to Week 4 in Polycythemia Vera Symptoms | Bone pain | -2.5 scores on a scale | Standard Deviation 0.71 |
| PV: Ruxolitinib 25 mg BID | Change From Baseline to Week 4 in Polycythemia Vera Symptoms | Night sweats | -2.8 scores on a scale | Standard Deviation 3.19 |
| PV: Ruxolitinib 50 mg QD | Change From Baseline to Week 4 in Polycythemia Vera Symptoms | Fever | -2.0 scores on a scale | Standard Deviation 1.41 |
| PV: Ruxolitinib 50 mg QD | Change From Baseline to Week 4 in Polycythemia Vera Symptoms | Itching (pruritus) | -2.8 scores on a scale | Standard Deviation 4.09 |
| PV: Ruxolitinib 50 mg QD | Change From Baseline to Week 4 in Polycythemia Vera Symptoms | Night sweats | -3.3 scores on a scale | Standard Deviation 1.15 |
| PV: Ruxolitinib 50 mg QD | Change From Baseline to Week 4 in Polycythemia Vera Symptoms | Bone pain | -4.3 scores on a scale | Standard Deviation 2.08 |
Secondary
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
Time frame: Baseline and 24 weeks (Cycle 7, Day 1)
Population: Essential thrombocythemia intent to treat population. 'N' indicates the number of patients for whom data was available for each component.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PV: Ruxolitinib 10 mg BID | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 24 Weeks | Absence of palpable splenomegaly | 100 percentage of participants |
| PV: Ruxolitinib 10 mg BID | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 24 Weeks | WBC count ≤ 10 x 10^9/L | 100 percentage of participants |
| PV: Ruxolitinib 10 mg BID | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 24 Weeks | 50% reduction in spleen size | 100 percentage of participants |
| PV: Ruxolitinib 10 mg BID | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 24 Weeks | Platelet count ≤ 400 x 10^9/L | 14 percentage of participants |
| PV: Ruxolitinib 25 mg BID | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 24 Weeks | 50% reduction in spleen size | 100 percentage of participants |
| PV: Ruxolitinib 25 mg BID | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 24 Weeks | Absence of palpable splenomegaly | 95 percentage of participants |
| PV: Ruxolitinib 25 mg BID | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 24 Weeks | Platelet count ≤ 400 x 10^9/L | 5 percentage of participants |
| PV: Ruxolitinib 25 mg BID | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 24 Weeks | WBC count ≤ 10 x 10^9/L | 86 percentage of participants |
| PV: Ruxolitinib 50 mg QD | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 24 Weeks | Absence of palpable splenomegaly | 100 percentage of participants |
| PV: Ruxolitinib 50 mg QD | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 24 Weeks | WBC count ≤ 10 x 10^9/L | 100 percentage of participants |
| PV: Ruxolitinib 50 mg QD | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 24 Weeks | 50% reduction in spleen size | 100 percentage of participants |
| PV: Ruxolitinib 50 mg QD | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 24 Weeks | Platelet count ≤ 400 x 10^9/L | 0 percentage of participants |
Secondary
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
Time frame: Baseline and 36 weeks (Cycle 10, Day 1)
Population: Essential thrombocythemia intent to treat population. 'N' indicates the number of patients for whom data was available for each component.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PV: Ruxolitinib 10 mg BID | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 36 Weeks | 50% reduction in spleen size | 100 percentage of participants |
| PV: Ruxolitinib 10 mg BID | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 36 Weeks | Platelet count ≤ 400 x 10^9/L | 14 percentage of participants |
| PV: Ruxolitinib 10 mg BID | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 36 Weeks | WBC count ≤ 10 x 10^9/L | 100 percentage of participants |
| PV: Ruxolitinib 10 mg BID | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 36 Weeks | Absence of palpable splenomegaly | 100 percentage of participants |
| PV: Ruxolitinib 25 mg BID | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 36 Weeks | Platelet count ≤ 400 x 10^9/L | 11 percentage of participants |
| PV: Ruxolitinib 25 mg BID | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 36 Weeks | 50% reduction in spleen size | 100 percentage of participants |
| PV: Ruxolitinib 25 mg BID | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 36 Weeks | Absence of palpable splenomegaly | 94 percentage of participants |
| PV: Ruxolitinib 25 mg BID | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 36 Weeks | WBC count ≤ 10 x 10^9/L | 79 percentage of participants |
| PV: Ruxolitinib 50 mg QD | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 36 Weeks | Absence of palpable splenomegaly | 100 percentage of participants |
| PV: Ruxolitinib 50 mg QD | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 36 Weeks | Platelet count ≤ 400 x 10^9/L | 14 percentage of participants |
| PV: Ruxolitinib 50 mg QD | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 36 Weeks | WBC count ≤ 10 x 10^9/L | 86 percentage of participants |
| PV: Ruxolitinib 50 mg QD | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 36 Weeks | 50% reduction in spleen size | 100 percentage of participants |
Secondary
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
Time frame: Baseline and 4 weeks (Cycle 2, Day 1)
Population: Essential thrombocythemia intent to treat population. 'N' indicates the number of patients for whom data was available for each component.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PV: Ruxolitinib 10 mg BID | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 4 Weeks | 50% reduction in spleen size | 83 percentage of participants |
| PV: Ruxolitinib 10 mg BID | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 4 Weeks | WBC count ≤ 10 x 10^9/L | 100 percentage of participants |
| PV: Ruxolitinib 10 mg BID | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 4 Weeks | Platelet count ≤ 400 x 10^9/L | 25 percentage of participants |
| PV: Ruxolitinib 10 mg BID | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 4 Weeks | Absence of palpable splenomegaly | 67 percentage of participants |
| PV: Ruxolitinib 25 mg BID | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 4 Weeks | WBC count ≤ 10 x 10^9/L | 100 percentage of participants |
| PV: Ruxolitinib 25 mg BID | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 4 Weeks | Platelet count ≤ 400 x 10^9/L | 41 percentage of participants |
| PV: Ruxolitinib 25 mg BID | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 4 Weeks | 50% reduction in spleen size | 95 percentage of participants |
| PV: Ruxolitinib 25 mg BID | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 4 Weeks | Absence of palpable splenomegaly | 89 percentage of participants |
| PV: Ruxolitinib 50 mg QD | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 4 Weeks | 50% reduction in spleen size | 100 percentage of participants |
| PV: Ruxolitinib 50 mg QD | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 4 Weeks | WBC count ≤ 10 x 10^9/L | 100 percentage of participants |
| PV: Ruxolitinib 50 mg QD | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 4 Weeks | Platelet count ≤ 400 x 10^9/L | 33 percentage of participants |
| PV: Ruxolitinib 50 mg QD | Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 4 Weeks | Absence of palpable splenomegaly | 100 percentage of participants |
Secondary
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
Time frame: Baseline and Week 12 (Cycle 4, Day 1)
Population: Polycythemia Vera intent to treat population for whom data was available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PV: Ruxolitinib 10 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 12 Weeks | 50% reduction in spleen size | 74 percentage of participants |
| PV: Ruxolitinib 10 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 12 Weeks | Hematocrit <45% Without Phlebotomy | 95 percentage of participants |
| PV: Ruxolitinib 10 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 12 Weeks | Absence of palpable splenomegaly | 68 percentage of participants |
| PV: Ruxolitinib 10 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 12 Weeks | Platelet count ≤ 400 x 10^9/L | 58 percentage of participants |
| PV: Ruxolitinib 10 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 12 Weeks | WBC count ≤ 10 x 10^9/L | 68 percentage of participants |
| PV: Ruxolitinib 25 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 12 Weeks | Hematocrit <45% Without Phlebotomy | 88 percentage of participants |
| PV: Ruxolitinib 25 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 12 Weeks | Absence of palpable splenomegaly | 50 percentage of participants |
| PV: Ruxolitinib 25 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 12 Weeks | 50% reduction in spleen size | 63 percentage of participants |
| PV: Ruxolitinib 25 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 12 Weeks | WBC count ≤ 10 x 10^9/L | 63 percentage of participants |
| PV: Ruxolitinib 25 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 12 Weeks | Platelet count ≤ 400 x 10^9/L | 50 percentage of participants |
| PV: Ruxolitinib 50 mg QD | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 12 Weeks | 50% reduction in spleen size | 86 percentage of participants |
| PV: Ruxolitinib 50 mg QD | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 12 Weeks | Hematocrit <45% Without Phlebotomy | 86 percentage of participants |
| PV: Ruxolitinib 50 mg QD | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 12 Weeks | WBC count ≤ 10 x 10^9/L | 43 percentage of participants |
| PV: Ruxolitinib 50 mg QD | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 12 Weeks | Platelet count ≤ 400 x 10^9/L | 57 percentage of participants |
| PV: Ruxolitinib 50 mg QD | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 12 Weeks | Absence of palpable splenomegaly | 57 percentage of participants |
Secondary
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
Time frame: Baseline and Week 24 (Cycle 7, Day 1)
Population: Polycythemia Vera intent to treat population for whom data was available. 'N' indicates the number of patients for whom data was available for each component.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PV: Ruxolitinib 10 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 24 Weeks | 50% reduction in spleen size | 78 percentage of participants |
| PV: Ruxolitinib 10 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 24 Weeks | Platelet count ≤ 400 x 10^9/L | 58 percentage of participants |
| PV: Ruxolitinib 10 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 24 Weeks | Absence of palpable splenomegaly | 61 percentage of participants |
| PV: Ruxolitinib 10 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 24 Weeks | WBC count ≤ 10 x 10^9/L | 74 percentage of participants |
| PV: Ruxolitinib 10 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 24 Weeks | Hematocrit <45% Without Phlebotomy | 100 percentage of participants |
| PV: Ruxolitinib 25 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 24 Weeks | Absence of palpable splenomegaly | 43 percentage of participants |
| PV: Ruxolitinib 25 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 24 Weeks | 50% reduction in spleen size | 71 percentage of participants |
| PV: Ruxolitinib 25 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 24 Weeks | Hematocrit <45% Without Phlebotomy | 88 percentage of participants |
| PV: Ruxolitinib 25 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 24 Weeks | Platelet count ≤ 400 x 10^9/L | 88 percentage of participants |
| PV: Ruxolitinib 25 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 24 Weeks | WBC count ≤ 10 x 10^9/L | 25 percentage of participants |
| PV: Ruxolitinib 50 mg QD | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 24 Weeks | WBC count ≤ 10 x 10^9/L | 86 percentage of participants |
| PV: Ruxolitinib 50 mg QD | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 24 Weeks | Platelet count ≤ 400 x 10^9/L | 86 percentage of participants |
| PV: Ruxolitinib 50 mg QD | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 24 Weeks | Absence of palpable splenomegaly | 71 percentage of participants |
| PV: Ruxolitinib 50 mg QD | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 24 Weeks | 50% reduction in spleen size | 100 percentage of participants |
| PV: Ruxolitinib 50 mg QD | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 24 Weeks | Hematocrit <45% Without Phlebotomy | 100 percentage of participants |
Secondary
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
Time frame: Baseline and Week 36 (Cycle 10, Day 1)
Population: Polycythemia Vera intent to treat population for whom data was available. 'N' indicates the number of patients for whom data was available for each component.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PV: Ruxolitinib 10 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 36 Weeks | Platelet count ≤ 400 x 10^9/L | 67 percentage of participants |
| PV: Ruxolitinib 10 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 36 Weeks | 50% reduction in spleen size | 76 percentage of participants |
| PV: Ruxolitinib 10 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 36 Weeks | Hematocrit <45% Without Phlebotomy | 100 percentage of participants |
| PV: Ruxolitinib 10 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 36 Weeks | Absence of palpable splenomegaly | 71 percentage of participants |
| PV: Ruxolitinib 10 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 36 Weeks | WBC count ≤ 10 x 10^9/L | 67 percentage of participants |
| PV: Ruxolitinib 25 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 36 Weeks | 50% reduction in spleen size | 71 percentage of participants |
| PV: Ruxolitinib 25 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 36 Weeks | Hematocrit <45% Without Phlebotomy | 88 percentage of participants |
| PV: Ruxolitinib 25 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 36 Weeks | Absence of palpable splenomegaly | 57 percentage of participants |
| PV: Ruxolitinib 25 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 36 Weeks | Platelet count ≤ 400 x 10^9/L | 75 percentage of participants |
| PV: Ruxolitinib 25 mg BID | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 36 Weeks | WBC count ≤ 10 x 10^9/L | 25 percentage of participants |
| PV: Ruxolitinib 50 mg QD | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 36 Weeks | WBC count ≤ 10 x 10^9/L | 71 percentage of participants |
| PV: Ruxolitinib 50 mg QD | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 36 Weeks | Platelet count ≤ 400 x 10^9/L | 86 percentage of participants |
| PV: Ruxolitinib 50 mg QD | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 36 Weeks | Hematocrit <45% Without Phlebotomy | 100 percentage of participants |
| PV: Ruxolitinib 50 mg QD | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 36 Weeks | 50% reduction in spleen size | 100 percentage of participants |
| PV: Ruxolitinib 50 mg QD | Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 36 Weeks | Absence of palpable splenomegaly | 86 percentage of participants |