Expanded Treatment Protocol (ETP) of Ruxolitinib in Patients With Polycythemia Vera Who Were Hydroxyurea Resistant or Intolerant and for Whom no Treatment Alternatives Was Available.
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT02292446
Collaborator
(none)
161
65
1
37.3
2.5
0.1
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
161 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label, Multi-center, Expanded Treatment Protocol (ETP) of Ruxolitinib in Patients With Polycythemia Vera Who Are Hydroxyurea Resistant or Intolerant and for Whom no Treatment Alternatives Are Available.
Actual Study Start Date
:
Nov 21, 2014
Actual Primary Completion Date
:
Dec 29, 2017
Actual Study Completion Date
:
Dec 29, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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 |
Drug: Ruxolitinib
supplied as 5 mg, 10 mg and 20 mg tablets to be taken orally
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Adverse Events - All Grades [Baseline up to approximately 26 months]
Summary of adverse events (all grades).
Secondary Outcome Measures
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Linz | Austria | A-4010 | |
| 2 | Novartis Investigative Site | Salzburg | Austria | 5020 | |
| 3 | Novartis Investigative Site | Wels | Austria | A 4600 | |
| 4 | Novartis Investigative Site | Antwerp | Belgium | 2060 | |
| 5 | Novartis Investigative Site | Brugge | Belgium | 8000 | |
| 6 | Novartis Investigative Site | Bruxelles | Belgium | 1070 | |
| 7 | Novartis Investigative Site | Leuven | Belgium | 3000 | |
| 8 | Novartis Investigative Site | Liege | Belgium | 4000 | |
| 9 | Novartis Investigative Site | Yvoir | Belgium | 5530 | |
| 10 | Novartis Investigative Site | Pleven | Bulgaria | 5800 | |
| 11 | Novartis Investigative Site | Plovdiv | Bulgaria | 4002 | |
| 12 | Novartis Investigative Site | Sofia | Bulgaria | 1413 | |
| 13 | Novartis Investigative Site | Sofia | Bulgaria | 1431 | |
| 14 | Novartis Investigative Site | Vancouver | British Columbia | Canada | V5Z 1M9 |
| 15 | Novartis Investigative Site | Hamilton | Ontario | Canada | L8V 5C2 |
| 16 | Novartis Investigative Site | Vina del Mar | Valparaiso | Chile | 2540364 |
| 17 | Novartis Investigative Site | Santiago | Chile | 8420383 | |
| 18 | Novartis Investigative Site | Santiago | Chile | ||
| 19 | Novartis Investigative Site | Bayonne | Bayonne Cedex | France | 64109 |
| 20 | Novartis Investigative Site | Le Mans | Cedex 09 | France | 72037 |
| 21 | Novartis Investigative Site | Angers Cedex 1 | France | 49033 | |
| 22 | Novartis Investigative Site | Avignon cedex 9 | France | 84902 | |
| 23 | Novartis Investigative Site | Bordeaux | France | 33076 | |
| 24 | Novartis Investigative Site | Chambéry Cedex | France | 73011 | |
| 25 | Novartis Investigative Site | Marseille | France | 13273 | |
| 26 | Novartis Investigative Site | Meaux cedex | France | 77104 | |
| 27 | Novartis Investigative Site | Metz | France | 57000 | |
| 28 | Novartis Investigative Site | Mulhouse cedex | France | 68070 | |
| 29 | Novartis Investigative Site | Nice Cedex | France | 06202 | |
| 30 | Novartis Investigative Site | Paris | France | 75010 | |
| 31 | Novartis Investigative Site | Perpignan | France | 66046 | |
| 32 | Novartis Investigative Site | Pringy cedex | France | 74374 | |
| 33 | Novartis Investigative Site | Toulouse Cedex 9 | France | 31059 | |
| 34 | Novartis Investigative Site | Vandoeuvre Les Nancy | France | 54511 | |
| 35 | Novartis Investigative Site | Villejuif Cedex | France | 94805 | |
| 36 | Novartis Investigative Site | Mannheim | Baden-Wuerttemberg | Germany | 68305 |
| 37 | Novartis Investigative Site | Aschaffenburg | Germany | 63739 | |
| 38 | Novartis Investigative Site | Augsburg | Germany | 86150 | |
| 39 | Novartis Investigative Site | Bad Soden | Germany | 65812 | |
| 40 | Novartis Investigative Site | Berlin | Germany | 13357 | |
| 41 | Novartis Investigative Site | Bottrop | Germany | 46236 | |
| 42 | Novartis Investigative Site | Eisenach | Germany | 99817 | |
| 43 | Novartis Investigative Site | Erlangen | Germany | 91054 | |
| 44 | Novartis Investigative Site | Frankfurt | Germany | 60389 | |
| 45 | Novartis Investigative Site | Frankfurt | Germany | 60596 | |
| 46 | Novartis Investigative Site | Friedrichshafen | Germany | 88045 | |
| 47 | Novartis Investigative Site | Hamburg | Germany | 22081 | |
| 48 | Novartis Investigative Site | Hamm | Germany | 59063 | |
| 49 | Novartis Investigative Site | Heidelberg | Germany | 69115 | |
| 50 | Novartis Investigative Site | Heilbronn | Germany | 74072 | |
| 51 | Novartis Investigative Site | Koblenz | Germany | 56068 | |
| 52 | Novartis Investigative Site | Mutlangen | Germany | 73557 | |
| 53 | Novartis Investigative Site | Stuttgart | Germany | 70376 | |
| 54 | Novartis Investigative Site | Wuerzburg | Germany | 97080 | |
| 55 | Novartis Investigative Site | Monterrey | Nuevo Leon | Mexico | 64000 |
| 56 | Novartis Investigative Site | Fredrikstad | Norway | NO-1603 | |
| 57 | Novartis Investigative Site | Tromso | Norway | 9038 | |
| 58 | Novartis Investigative Site | Lisboa | Portugal | 1099 023 | |
| 59 | Novartis Investigative Site | Lisboa | Portugal | 1749-035 | |
| 60 | Novartis Investigative Site | Lulea | Sweden | SE 971 80 | |
| 61 | Novartis Investigative Site | Uddevalla | Sweden | 451 80 | |
| 62 | Novartis Investigative Site | Khon Kaen | THA | Thailand | 40002 |
| 63 | Novartis Investigative Site | Bangkok | Thailand | 10400 | |
| 64 | Novartis Investigative Site | Bangkok | Thailand | 10700 | |
| 65 | Novartis Investigative Site | Chiang Mai | Thailand | 50200 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02292446
Other Study ID Numbers:
- CINC424B2001X
First Posted:
Nov 17, 2014
Last Update Posted:
Jul 18, 2019
Last Verified:
Jul 1, 2019
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 161 patients were included in the ruxolitinib arm and 100% of the patient's received the treatment |
| Arm/Group Title | All Patients |
|---|---|
| Arm/Group Description | 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 |
| Period Title: Overall Study | |
| STARTED | 161 |
| COMPLETED | 141 |
| NOT COMPLETED | 20 |
Baseline Characteristics
| Arm/Group Title | All Patients |
|---|---|
| Arm/Group Description | 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 |
| Overall Participants | 161 |
| Age, Customized (participants) [Number] | |
| <= 60 |
52
32.3%
|
| >60 |
109
67.7%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
65
40.4%
|
| Male |
96
59.6%
|
| Race/Ethnicity, Customized (participants) [Number] | |
| Caucasian |
128
79.5%
|
| Asian |
3
1.9%
|
| Other |
30
18.6%
|
| Number of participants resistant or intolerant to hydroxyurea (HU) (participants) [Number] | |
| Resistant to hydroxyurea |
60
37.3%
|
| Intolerant to hydroxyurea |
101
62.7%
|
| Number of participants' frequency of phlebotomy in 52 weeks prior to screening (participants) [Number] | |
| 1 phlebotomy |
21
13%
|
| 2 phlebotomies |
19
11.8%
|
| >=3 phlebotomies |
74
46%
|
| Missing |
47
29.2%
|
| Number of participants' use of prior antineoplastic therapy (participants) [Number] | |
| Prior Hydroxyurea use |
160
99.4%
|
| Prior other anti-neoplastic medications use |
59
36.6%
|
Outcome Measures
| Title | Number of Participants With Adverse Events - All Grades |
|---|---|
| Description | Summary of adverse events (all grades). |
| Time Frame | Baseline up to approximately 26 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | All Patients |
|---|---|
| Arm/Group Description | 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 |
| Measure Participants | 161 |
| Adverse events |
143
88.8%
|
| Serious adverse events |
26
16.1%
|
| Title | Change From Baseline in Hematocrit Levels at All Visits |
|---|---|
| Description | Change in hematocrit levels from Baseline to each visit were measured |
| Time Frame | Up to approximately 26 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants qualifying for evaluation of change from baseline varied across visits |
| Arm/Group Title | Baseline | Post-baseline | Change |
|---|---|---|---|
| Arm/Group Description | Hematocrit level at baseline | Post-baseline hematocrit value | Change from baseline |
| Measure Participants | 161 | 161 | 161 |
| Week 4 |
45.26
(5.246)
|
43.70
(5.220)
|
-1.55
(3.652)
|
| Week 8 |
45.21
(5.136)
|
40.73
(4.967)
|
-4.48
(5.055)
|
| Week 12 |
45.44
(5.324)
|
39.97
(5.419)
|
-5.47
(6.522)
|
| Week 16 |
45.64
(5.395)
|
39.32
(5.454)
|
-6.32
(6.928)
|
| Week 20 |
45.96
(5.353)
|
40.47
(5.323)
|
-5.49
(6.840)
|
| Week 24 |
45.93
(5.109)
|
40.32
(4.960)
|
-5.62
(6.073)
|
| Week 36 |
45.30
(4.602)
|
40.43
(4.959)
|
-4.86
(6.184)
|
| Week 48 |
45.41
(4.714)
|
39.82
(4.959)
|
-5.59
(6.318)
|
| Week 60 |
46.56
(5.299)
|
40.60
(5.105)
|
40.60
(5.929)
|
| Week 72 |
47.66
(5.377)
|
40.59
(4.056)
|
-7.07
(6.388)
|
| Week 84 |
48.15
(5.758)
|
41.93
(5.097)
|
-6.23
(6.492)
|
| Week 96 |
50.03
(4.702)
|
40.82
(4.496)
|
-9.21
(6.861)
|
| EOT |
45.38
(5.202)
|
39.93
(5.730)
|
-5.45
(5.847)
|
| Title | Change From Baseline in Spleen Length |
|---|---|
| Description | Change in spleen length from Baseline to each visit |
| Time Frame | Up to approximately 26 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants qualifying for evaluation of change from baseline varied across visits |
| Arm/Group Title | Baseline | Post-baseline | Change |
|---|---|---|---|
| Arm/Group Description | Hematocrit level at baseline | Post-baseline hematocrit value | Change from baseline |
| Measure Participants | 161 | 161 | 161 |
| Week 12 |
23.92
(14.618)
|
16.83
(12.931)
|
-7.09
(12.770)
|
| Week 24 |
22.66
(14.319)
|
16.26
(13.896)
|
-6.40
(14.101)
|
| Week 36 |
21.87
(13.228)
|
16.70
(14.419)
|
-5.18
(10.929)
|
| Week 48 |
22.14
(13.994)
|
18.76
(16.880)
|
-3.38
(14.438)
|
| Week 60 |
20.00
(13.007)
|
17.35
(12.357)
|
-2.65
(13.753)
|
| Week 72 |
18.41
(13.148)
|
13.47
(11.441)
|
-4.94
(13.840)
|
| Week 84 |
19.57
(14.233)
|
13.36
(9.443)
|
-6.21
(12.135)
|
| Week 96 |
19.92
(14.494)
|
12.33
(8.026)
|
-7.58
(11.237)
|
| End of treatment |
3.03
(3.419)
|
0.54
(1.661)
|
-2.49
(3.025)
|
| Title | Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants qualifying for evaluation of change from baseline varied across visits |
| Arm/Group Title | Baseline | Post-baseline | Change |
|---|---|---|---|
| Arm/Group Description | Hematocrit level at baseline | Post-baseline hematocrit value | Change from baseline |
| Measure Participants | 161 | 161 | 161 |
| Week 12 |
23.92
(14.618)
|
16.83
(12.931)
|
-7.09
(12.770)
|
| Week 24 |
22.66
(14.319)
|
16.26
(13.896)
|
-6.40
(14.101)
|
| Week 36 |
21.87
(13.228)
|
16.70
(14.419)
|
-5.18
(10.929)
|
| Week 48 |
22.14
(13.994)
|
18.76
(16.880)
|
-3.38
(14.438)
|
| Week 60 |
20.00
(13.007)
|
17.35
(12.357)
|
-2.65
(13.753)
|
| Week 72 |
18.41
(13.148)
|
13.47
(11.441)
|
-4.94
(13.840)
|
| Week 84 |
19.57
(14.233)
|
13.36
(9.443)
|
-6.21
(12.135)
|
| Week 96 |
19.92
(14.494)
|
12.33
(8.026)
|
-7.58
(11.237)
|
| End of treatment |
22.86
(14.225)
|
18.12
(15.130)
|
-4.74
(13.954)
|
Adverse Events
| Time Frame | Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 26 months | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | All Patients | |
| Arm/Group Description | 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 | |
All Cause Mortality |
||
| All Patients | ||
| Affected / at Risk (%) | # Events | |
| Total | 1/161 (0.6%) | |
Serious Adverse Events |
||
| All Patients | ||
| Affected / at Risk (%) | # Events | |
| Total | 26/161 (16.1%) | |
| Blood and lymphatic system disorders | ||
| Anaemia | 2/161 (1.2%) | |
| Cardiac disorders | ||
| Bundle branch block bilateral | 1/161 (0.6%) | |
| Pericarditis | 1/161 (0.6%) | |
| Ventricular extrasystoles | 1/161 (0.6%) | |
| Eye disorders | ||
| Cataract | 1/161 (0.6%) | |
| Gastrointestinal disorders | ||
| Ascites | 1/161 (0.6%) | |
| Diarrhoea | 1/161 (0.6%) | |
| Retroperitoneal haematoma | 1/161 (0.6%) | |
| Umbilical hernia | 1/161 (0.6%) | |
| Upper gastrointestinal haemorrhage | 1/161 (0.6%) | |
| General disorders | ||
| Pyrexia | 1/161 (0.6%) | |
| Infections and infestations | ||
| Appendicitis | 1/161 (0.6%) | |
| Diverticulitis | 1/161 (0.6%) | |
| Pneumonia | 2/161 (1.2%) | |
| Prostatitis Escherichia coli | 1/161 (0.6%) | |
| Injury, poisoning and procedural complications | ||
| Accident | 1/161 (0.6%) | |
| Acetabulum fracture | 1/161 (0.6%) | |
| Overdose | 1/161 (0.6%) | |
| Skin injury | 1/161 (0.6%) | |
| Tendon rupture | 1/161 (0.6%) | |
| Musculoskeletal and connective tissue disorders | ||
| Arthralgia | 1/161 (0.6%) | |
| Osteoarthritis | 1/161 (0.6%) | |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
| Acute myeloid leukaemia | 1/161 (0.6%) | |
| Malignant melanoma | 1/161 (0.6%) | |
| Renal cancer | 1/161 (0.6%) | |
| Squamous cell carcinoma | 2/161 (1.2%) | |
| Nervous system disorders | ||
| Dizziness | 1/161 (0.6%) | |
| Seizure | 1/161 (0.6%) | |
| Psychiatric disorders | ||
| Depression | 1/161 (0.6%) | |
| Renal and urinary disorders | ||
| Dysuria | 1/161 (0.6%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Dyspnoea | 1/161 (0.6%) | |
Other (Not Including Serious) Adverse Events |
||
| All Patients | ||
| Affected / at Risk (%) | # Events | |
| Total | 107/161 (66.5%) | |
| Blood and lymphatic system disorders | ||
| Anaemia | 35/161 (21.7%) | |
| Thrombocytosis | 11/161 (6.8%) | |
| Gastrointestinal disorders | ||
| Constipation | 14/161 (8.7%) | |
| Diarrhoea | 15/161 (9.3%) | |
| General disorders | ||
| Asthenia | 12/161 (7.5%) | |
| Fatigue | 14/161 (8.7%) | |
| Infections and infestations | ||
| Nasopharyngitis | 9/161 (5.6%) | |
| Investigations | ||
| Weight increased | 13/161 (8.1%) | |
| Nervous system disorders | ||
| Dizziness | 12/161 (7.5%) | |
| Headache | 27/161 (16.8%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Dyspnoea | 9/161 (5.6%) | |
| Epistaxis | 9/161 (5.6%) | |
| Skin and subcutaneous tissue disorders | ||
| Pruritus | 13/161 (8.1%) | |
| Vascular disorders | ||
| Hypertension | 9/161 (5.6%) | |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novaratis Pharmaceuticals |
| Phone | 888-669-6682 |
| novartis.email@novartis.com |
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02292446
Other Study ID Numbers:
- CINC424B2001X
First Posted:
Nov 17, 2014
Last Update Posted:
Jul 18, 2019
Last Verified:
Jul 1, 2019