Polycythemia Vera
Conditions
Keywords
Polycythemia Vera, Hematologic Diseases, Myeloproliferative Disorders, INC424, Ruxolitinib, hydroxyurea resistant, adult
Brief summary
The purpose of this open-label, single arm, multi-center Expanded Treatment Protocol (ETP) was to provide early access to ruxolitinib and evaluate safety information in patients with polycythemia vera (PV) who were hydroxyurea (HU) resistant or intolerant and who had no other standard treatment option, nor did they qualify for another clinical study for PV
Interventions
DRUGRuxolitinib
supplied as 5 mg, 10 mg and 20 mg tablets to be taken orally
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
•Confirmed diagnosis of PV according to the 2008 World Health Organization criteria, palpable spleen, Resistant to or intolerant of hydroxyurea, ECOG performance status of 0, 1 or 2; did not have access to a comparable or satisfactory alternative treatment
Exclusion criteria
•Inadequate liver or renal function, Significant bacterial, fungal, parasitic, or viral infection requiring treatment, Active malignancy within the past 5 years, except treated cervical intraepithelial neoplasia, basal cell carcinoma of the skin, or squamous cell carcinoma of the skin, with no evidence for recurrence in the past 3 years., Women who were pregnant or nursing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events - All Grades | Baseline up to approximately 26 months | Summary of adverse events (all grades). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hematocrit Levels at All Visits | Up to approximately 26 months | Change in hematocrit levels from Baseline to each visit were measured |
| Change From Baseline in Spleen Length | Up to approximately 26 months | Change in spleen length from Baseline to each visit |
| Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | Up to approximately 26 months | The MPN-SAF (Appendix 6) was a disease specific questionnaire comprised of 10 items that measures fatigue related to MPN disease and the severity of nine of the most prevalent associated symptoms including: early satiety, abdominal discomfort, inactivity, concentration, night sweats, itching, bone pain, fever and weight loss. There were three recall periods used in this questionnaire, which were 24 hours for fatigue, the past week for symptoms of early satiety, abdominal discomfort, inactivity, concentration, night sweats, itching, bone pain and fever, and the past 6 months for weight loss, Each item was scored on a scale ranging from 0 (no fatigue/absent) to 10 (As bad as you can imagine/worst imaginable). The MPN-SAF TSS was computed as the average of the observed items multiplied by 10 to achieve a 0-to-100 scale. The MPN-SAF TSS thus had a possible score range of 0 to 100. |
Countries
Austria, Belgium, Bulgaria, Canada, Chile, France, Germany, Mexico, Norway, Portugal, Sweden, Thailand
Participant flow
Pre-assignment details
161 patients were included in the ruxolitinib arm and 100% of the patient's received the treatment
Participants by arm
| Arm | Count |
|---|---|
| All Patients All patients will receive ruxolitinib at a starting dose of 10 mg twice daily which could be titrated to most appropriate dose. Dose was not to exceed 25 mg bid nor be less than 5 mg once a day | 161 |
| Total | 161 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 12 |
| Overall Study | Death | 1 |
| Overall Study | Disease progression | 2 |
| Overall Study | Subject/guardian decision | 2 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | All Patients |
|---|---|
| Age, Customized <= 60 | 52 participants |
| Age, Customized >60 | 109 participants |
| Number of participants' frequency of phlebotomy in 52 weeks prior to screening 1 phlebotomy | 21 participants |
| Number of participants' frequency of phlebotomy in 52 weeks prior to screening 2 phlebotomies | 19 participants |
| Number of participants' frequency of phlebotomy in 52 weeks prior to screening >=3 phlebotomies | 74 participants |
| Number of participants' frequency of phlebotomy in 52 weeks prior to screening Missing | 47 participants |
| Number of participants resistant or intolerant to hydroxyurea (HU) Intolerant to hydroxyurea | 101 participants |
| Number of participants resistant or intolerant to hydroxyurea (HU) Resistant to hydroxyurea | 60 participants |
| Number of participants' use of prior antineoplastic therapy Prior Hydroxyurea use | 160 participants |
| Number of participants' use of prior antineoplastic therapy Prior other anti-neoplastic medications use | 59 participants |
| Race/Ethnicity, Customized Asian | 3 participants |
| Race/Ethnicity, Customized Caucasian | 128 participants |
| Race/Ethnicity, Customized Other | 30 participants |
| Sex: Female, Male Female | 65 Participants |
| Sex: Female, Male Male | 96 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 161 |
| other Total, other adverse events | 107 / 161 |
| serious Total, serious adverse events | 26 / 161 |
Outcome results
Primary
Number of Participants With Adverse Events - All Grades
Summary of adverse events (all grades).
Time frame: Baseline up to approximately 26 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Patients | Number of Participants With Adverse Events - All Grades | Serious adverse events | 26 Participants |
| All Patients | Number of Participants With Adverse Events - All Grades | Adverse events | 143 Participants |
Secondary
Change From Baseline in Hematocrit Levels at All Visits
Change in hematocrit levels from Baseline to each visit were measured
Time frame: Up to approximately 26 months
Population: Number of participants qualifying for evaluation of change from baseline varied across visits
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Patients | Change From Baseline in Hematocrit Levels at All Visits | Week 96 | 50.03 percentage | Standard Deviation 4.702 |
| All Patients | Change From Baseline in Hematocrit Levels at All Visits | Week 60 | 46.56 percentage | Standard Deviation 5.299 |
| All Patients | Change From Baseline in Hematocrit Levels at All Visits | Week 24 | 45.93 percentage | Standard Deviation 5.109 |
| All Patients | Change From Baseline in Hematocrit Levels at All Visits | Week 12 | 45.44 percentage | Standard Deviation 5.324 |
| All Patients | Change From Baseline in Hematocrit Levels at All Visits | Week 48 | 45.41 percentage | Standard Deviation 4.714 |
| All Patients | Change From Baseline in Hematocrit Levels at All Visits | Week 36 | 45.30 percentage | Standard Deviation 4.602 |
| All Patients | Change From Baseline in Hematocrit Levels at All Visits | Week 4 | 45.26 percentage | Standard Deviation 5.246 |
| All Patients | Change From Baseline in Hematocrit Levels at All Visits | Week 8 | 45.21 percentage | Standard Deviation 5.136 |
| All Patients | Change From Baseline in Hematocrit Levels at All Visits | Week 84 | 48.15 percentage | Standard Deviation 5.758 |
| All Patients | Change From Baseline in Hematocrit Levels at All Visits | Week 16 | 45.64 percentage | Standard Deviation 5.395 |
| All Patients | Change From Baseline in Hematocrit Levels at All Visits | EOT | 45.38 percentage | Standard Deviation 5.202 |
| All Patients | Change From Baseline in Hematocrit Levels at All Visits | Week 72 | 47.66 percentage | Standard Deviation 5.377 |
| All Patients | Change From Baseline in Hematocrit Levels at All Visits | Week 20 | 45.96 percentage | Standard Deviation 5.353 |
| Post-baseline | Change From Baseline in Hematocrit Levels at All Visits | Week 36 | 40.43 percentage | Standard Deviation 4.959 |
| Post-baseline | Change From Baseline in Hematocrit Levels at All Visits | Week 4 | 43.70 percentage | Standard Deviation 5.22 |
| Post-baseline | Change From Baseline in Hematocrit Levels at All Visits | Week 8 | 40.73 percentage | Standard Deviation 4.967 |
| Post-baseline | Change From Baseline in Hematocrit Levels at All Visits | Week 12 | 39.97 percentage | Standard Deviation 5.419 |
| Post-baseline | Change From Baseline in Hematocrit Levels at All Visits | Week 16 | 39.32 percentage | Standard Deviation 5.454 |
| Post-baseline | Change From Baseline in Hematocrit Levels at All Visits | Week 20 | 40.47 percentage | Standard Deviation 5.323 |
| Post-baseline | Change From Baseline in Hematocrit Levels at All Visits | Week 24 | 40.32 percentage | Standard Deviation 4.96 |
| Post-baseline | Change From Baseline in Hematocrit Levels at All Visits | Week 48 | 39.82 percentage | Standard Deviation 4.959 |
| Post-baseline | Change From Baseline in Hematocrit Levels at All Visits | Week 60 | 40.60 percentage | Standard Deviation 5.105 |
| Post-baseline | Change From Baseline in Hematocrit Levels at All Visits | Week 72 | 40.59 percentage | Standard Deviation 4.056 |
| Post-baseline | Change From Baseline in Hematocrit Levels at All Visits | Week 84 | 41.93 percentage | Standard Deviation 5.097 |
| Post-baseline | Change From Baseline in Hematocrit Levels at All Visits | Week 96 | 40.82 percentage | Standard Deviation 4.496 |
| Post-baseline | Change From Baseline in Hematocrit Levels at All Visits | EOT | 39.93 percentage | Standard Deviation 5.73 |
| Change | Change From Baseline in Hematocrit Levels at All Visits | Week 60 | 40.60 percentage | Standard Deviation 5.929 |
| Change | Change From Baseline in Hematocrit Levels at All Visits | Week 16 | -6.32 percentage | Standard Deviation 6.928 |
| Change | Change From Baseline in Hematocrit Levels at All Visits | Week 96 | -9.21 percentage | Standard Deviation 6.861 |
| Change | Change From Baseline in Hematocrit Levels at All Visits | Week 72 | -7.07 percentage | Standard Deviation 6.388 |
| Change | Change From Baseline in Hematocrit Levels at All Visits | Week 12 | -5.47 percentage | Standard Deviation 6.522 |
| Change | Change From Baseline in Hematocrit Levels at All Visits | Week 4 | -1.55 percentage | Standard Deviation 3.652 |
| Change | Change From Baseline in Hematocrit Levels at All Visits | Week 84 | -6.23 percentage | Standard Deviation 6.492 |
| Change | Change From Baseline in Hematocrit Levels at All Visits | Week 36 | -4.86 percentage | Standard Deviation 6.184 |
| Change | Change From Baseline in Hematocrit Levels at All Visits | Week 24 | -5.62 percentage | Standard Deviation 6.073 |
| Change | Change From Baseline in Hematocrit Levels at All Visits | Week 8 | -4.48 percentage | Standard Deviation 5.055 |
| Change | Change From Baseline in Hematocrit Levels at All Visits | Week 48 | -5.59 percentage | Standard Deviation 6.318 |
| Change | Change From Baseline in Hematocrit Levels at All Visits | Week 20 | -5.49 percentage | Standard Deviation 6.84 |
| Change | Change From Baseline in Hematocrit Levels at All Visits | EOT | -5.45 percentage | Standard Deviation 5.847 |
Secondary
Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)
The MPN-SAF (Appendix 6) was a disease specific questionnaire comprised of 10 items that measures fatigue related to MPN disease and the severity of nine of the most prevalent associated symptoms including: early satiety, abdominal discomfort, inactivity, concentration, night sweats, itching, bone pain, fever and weight loss. There were three recall periods used in this questionnaire, which were 24 hours for fatigue, the past week for symptoms of early satiety, abdominal discomfort, inactivity, concentration, night sweats, itching, bone pain and fever, and the past 6 months for weight loss, Each item was scored on a scale ranging from 0 (no fatigue/absent) to 10 (As bad as you can imagine/worst imaginable). The MPN-SAF TSS was computed as the average of the observed items multiplied by 10 to achieve a 0-to-100 scale. The MPN-SAF TSS thus had a possible score range of 0 to 100.
Time frame: Up to approximately 26 months
Population: Number of participants qualifying for evaluation of change from baseline varied across visits
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Patients | Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | Week 48 | 22.14 scores | Standard Deviation 13.994 |
| All Patients | Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | End of treatment | 22.86 scores | Standard Deviation 14.225 |
| All Patients | Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | Week 72 | 18.41 scores | Standard Deviation 13.148 |
| All Patients | Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | Week 60 | 20.00 scores | Standard Deviation 13.007 |
| All Patients | Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | Week 12 | 23.92 scores | Standard Deviation 14.618 |
| All Patients | Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | Week 96 | 19.92 scores | Standard Deviation 14.494 |
| All Patients | Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | Week 36 | 21.87 scores | Standard Deviation 13.228 |
| All Patients | Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | Week 24 | 22.66 scores | Standard Deviation 14.319 |
| All Patients | Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | Week 84 | 19.57 scores | Standard Deviation 14.233 |
| Post-baseline | Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | Week 60 | 17.35 scores | Standard Deviation 12.357 |
| Post-baseline | Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | Week 12 | 16.83 scores | Standard Deviation 12.931 |
| Post-baseline | Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | Week 24 | 16.26 scores | Standard Deviation 13.896 |
| Post-baseline | Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | Week 36 | 16.70 scores | Standard Deviation 14.419 |
| Post-baseline | Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | Week 48 | 18.76 scores | Standard Deviation 16.88 |
| Post-baseline | Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | Week 72 | 13.47 scores | Standard Deviation 11.441 |
| Post-baseline | Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | Week 84 | 13.36 scores | Standard Deviation 9.443 |
| Post-baseline | Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | Week 96 | 12.33 scores | Standard Deviation 8.026 |
| Post-baseline | Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | End of treatment | 18.12 scores | Standard Deviation 15.13 |
| Change | Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | Week 36 | -5.18 scores | Standard Deviation 10.929 |
| Change | Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | Week 12 | -7.09 scores | Standard Deviation 12.77 |
| Change | Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | Week 84 | -6.21 scores | Standard Deviation 12.135 |
| Change | Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | Week 24 | -6.40 scores | Standard Deviation 14.101 |
| Change | Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | End of treatment | -4.74 scores | Standard Deviation 13.954 |
| Change | Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | Week 60 | -2.65 scores | Standard Deviation 13.753 |
| Change | Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | Week 48 | -3.38 scores | Standard Deviation 14.438 |
| Change | Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | Week 96 | -7.58 scores | Standard Deviation 11.237 |
| Change | Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | Week 72 | -4.94 scores | Standard Deviation 13.84 |
Secondary
Change From Baseline in Spleen Length
Change in spleen length from Baseline to each visit
Time frame: Up to approximately 26 months
Population: Number of participants qualifying for evaluation of change from baseline varied across visits
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Patients | Change From Baseline in Spleen Length | Week 48 | 22.14 cm | Standard Deviation 13.994 |
| All Patients | Change From Baseline in Spleen Length | End of treatment | 3.03 cm | Standard Deviation 3.419 |
| All Patients | Change From Baseline in Spleen Length | Week 72 | 18.41 cm | Standard Deviation 13.148 |
| All Patients | Change From Baseline in Spleen Length | Week 60 | 20.00 cm | Standard Deviation 13.007 |
| All Patients | Change From Baseline in Spleen Length | Week 12 | 23.92 cm | Standard Deviation 14.618 |
| All Patients | Change From Baseline in Spleen Length | Week 96 | 19.92 cm | Standard Deviation 14.494 |
| All Patients | Change From Baseline in Spleen Length | Week 36 | 21.87 cm | Standard Deviation 13.228 |
| All Patients | Change From Baseline in Spleen Length | Week 24 | 22.66 cm | Standard Deviation 14.319 |
| All Patients | Change From Baseline in Spleen Length | Week 84 | 19.57 cm | Standard Deviation 14.233 |
| Post-baseline | Change From Baseline in Spleen Length | Week 60 | 17.35 cm | Standard Deviation 12.357 |
| Post-baseline | Change From Baseline in Spleen Length | Week 12 | 16.83 cm | Standard Deviation 12.931 |
| Post-baseline | Change From Baseline in Spleen Length | Week 24 | 16.26 cm | Standard Deviation 13.896 |
| Post-baseline | Change From Baseline in Spleen Length | Week 36 | 16.70 cm | Standard Deviation 14.419 |
| Post-baseline | Change From Baseline in Spleen Length | Week 48 | 18.76 cm | Standard Deviation 16.88 |
| Post-baseline | Change From Baseline in Spleen Length | Week 72 | 13.47 cm | Standard Deviation 11.441 |
| Post-baseline | Change From Baseline in Spleen Length | Week 84 | 13.36 cm | Standard Deviation 9.443 |
| Post-baseline | Change From Baseline in Spleen Length | Week 96 | 12.33 cm | Standard Deviation 8.026 |
| Post-baseline | Change From Baseline in Spleen Length | End of treatment | 0.54 cm | Standard Deviation 1.661 |
| Change | Change From Baseline in Spleen Length | Week 36 | -5.18 cm | Standard Deviation 10.929 |
| Change | Change From Baseline in Spleen Length | Week 12 | -7.09 cm | Standard Deviation 12.77 |
| Change | Change From Baseline in Spleen Length | Week 84 | -6.21 cm | Standard Deviation 12.135 |
| Change | Change From Baseline in Spleen Length | Week 24 | -6.40 cm | Standard Deviation 14.101 |
| Change | Change From Baseline in Spleen Length | End of treatment | -2.49 cm | Standard Deviation 3.025 |
| Change | Change From Baseline in Spleen Length | Week 60 | -2.65 cm | Standard Deviation 13.753 |
| Change | Change From Baseline in Spleen Length | Week 48 | -3.38 cm | Standard Deviation 14.438 |
| Change | Change From Baseline in Spleen Length | Week 96 | -7.58 cm | Standard Deviation 11.237 |
| Change | Change From Baseline in Spleen Length | Week 72 | -4.94 cm | Standard Deviation 13.84 |