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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02038036




Registration number
NCT02038036
Ethics application status
Date submitted
14/01/2014
Date registered
16/01/2014
Date last updated
20/07/2021

Titles & IDs
Public title
Ruxolitinib Efficacy and Safety in Patients With HU Resistant or Intolerant Polycythemia Vera vs Best Available Therapy.
Scientific title
Randomized, Open Label, Multicenter Phase IIIb Study Evaluating the Efficacy and Safety of Ruxolitinib Versus Best Available Therapy in Patients With Polycythemia Vera Who Are Hydroxyurea Resistant or Intolerant (Response 2)
Secondary ID [1] 0 0
CINC424B2401
Universal Trial Number (UTN)
Trial acronym
RESPONSE-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Polycythemia Vera 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Best Available Therapy
Treatment: Drugs - Ruxolitinib

Experimental: Ruxolitinib - Ruxolitinib was administered at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid.

Active Comparator: Best Available Therapy (BAT) - Best Available Therapy as selected by the investigator from: Hydroxyurea, Pegylated-Interferon (IFN/PEG-IFN), pipobroman, anagrelide, IMIDs, or observation. Participants randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib.


Treatment: Drugs: Best Available Therapy
Best Available Therapy as selected by the investigator from: Hydroxyurea, Pegylated-Interferon (IFN/PEG-IFN), pipobroman, anagrelide, IMIDs, or observation. Participants randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib.

Treatment: Drugs: Ruxolitinib
Ruxolitinib was administered at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants Achieving Hematocrit (Hct) Control at Week 28
Timepoint [1] 0 0
Week 28
Secondary outcome [1] 0 0
Number of Participants Achieving a Complete Hematological Remission at Week 28
Timepoint [1] 0 0
Week 28
Secondary outcome [2] 0 0
Number of Participants Achieving a Hematocrit (Hct) Control at Week 52 and Week 80
Timepoint [2] 0 0
Week 52 and 80
Secondary outcome [3] 0 0
Number of Participants Achieving a Complete Hematological Remission at Week 52 and Week 80
Timepoint [3] 0 0
Week 52 and 80
Secondary outcome [4] 0 0
Number of Participants With Phlebotomies Over Time
Timepoint [4] 0 0
Baseline to Week 260
Secondary outcome [5] 0 0
Change From Baseline in Hematocrit (Hct) at Each Visit
Timepoint [5] 0 0
Baseline, Week 4, 8, 12, 16, 20, 24, 28, 40, 52, 66, 80, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234, 247 and 260
Secondary outcome [6] 0 0
Change From Baseline in Hematocrit (Hct) at Each Scheduled Visit After Crossover in Participants Randomized to BAT Who Cross Over to Ruxolitinib
Timepoint [6] 0 0
Baseline (last assessment before cross over), Week 4, 8, 12, 16, 20, 24, 28, 40, 52, 64, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206, 219 and 232 after cross-over
Secondary outcome [7] 0 0
Spleen Length by Visit
Timepoint [7] 0 0
Week 4, 8, 12, 16, 20, 24, 28, 40, 52, 66, 80, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234, 247 and 260
Secondary outcome [8] 0 0
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status to Week 28
Timepoint [8] 0 0
Baseline and Week 28
Secondary outcome [9] 0 0
Number of Participants Achieving a Partial Remission Based on the European Leukemia Net (ELN) and International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) Criteria at Week 28
Timepoint [9] 0 0
Week 28
Secondary outcome [10] 0 0
Number of Participants Who Achieved Partial Remission Based on the European Leukemia Net (ELN) and International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) Criteria at Week 52 and Week 80
Timepoint [10] 0 0
Week 52 and 80
Secondary outcome [11] 0 0
Number of Participants Achieving a Hematocrit (Hct) Control at Week 104, Week 156, Week 208 and Week 260.
Timepoint [11] 0 0
From Week 8 to Week 104, 156, 208 and 260
Secondary outcome [12] 0 0
Number of Participants Achieving a Complete Hematological Remission at Week 104, Week 156, Week 208 and Week 260
Timepoint [12] 0 0
From Week 8 to Week 104, 156, 208 and 260
Secondary outcome [13] 0 0
Number of Participants Who Achieved Partial Remission Based on the European Leukemia Net (ELN) and International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) Criteria at Week 104, Week 156, Week 208 and Week 260.
Timepoint [13] 0 0
From Week 8 to Week 104, 156, 208 and 260
Secondary outcome [14] 0 0
Number of Participants With Transformation Free Survival Events
Timepoint [14] 0 0
Week 260 (ruxolitinib arm) and Week 80 (BAT arm)
Secondary outcome [15] 0 0
Number of Participants With Overall Survival (OS) Events
Timepoint [15] 0 0
up to Week 260
Secondary outcome [16] 0 0
Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)
Timepoint [16] 0 0
Baseline, Week 4, 8, 16, 28, 40, 52, 80, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234 and 247
Secondary outcome [17] 0 0
Change From Baseline in Total Scores of MPN-SAF by Visit in Patients From BAT Group Who Cross Over to Ruxolitinib After Crossover
Timepoint [17] 0 0
Baseline (last assessment before cross over), Week 4, 8, 16, 24, 28, 40, 52, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234 and 247 after cross-over
Secondary outcome [18] 0 0
Change From Baseline in Score as Per European Quality of Life 5-Dimension 5-level (EQ-5D-5L) Questionnaire
Timepoint [18] 0 0
Baseline, Week 4, 8, 16, 28, 52, 80, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234 and 247
Secondary outcome [19] 0 0
Change From Baseline in EQ-5D-5L VAS, by Visit in Patients From BAT Group Who Cross Over to Ruxolitinib After Crossover
Timepoint [19] 0 0
Baseline (last assessment before cross over), Week 4, 8, 16, 24, 28, 52, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234 and 247 after cross-over
Secondary outcome [20] 0 0
Change From Baseline in Work Productivity and Activity Impairment (WPAI) Questionnaire
Timepoint [20] 0 0
Baseline, Week 4, 8, 16, 28, 52 and 80
Secondary outcome [21] 0 0
Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI), by Visit in Patients From BAT Group Who Cross Over to Ruxolitinib After Crossover
Timepoint [21] 0 0
Baseline (last assessment before cross over), Week 4, 8, 16, 24, 28 and 52 after cross-over
Secondary outcome [22] 0 0
Patient Global Impression of Change (PGIC)
Timepoint [22] 0 0
Week 4, 8, 16, 28, 40, 52 and 80
Secondary outcome [23] 0 0
Summary of Patient Global Impression of Change (PGIC), by Visit in Patients From BAT Group Who Cross Over to Ruxolitinib After Crossover
Timepoint [23] 0 0
Baseline (last assessment before cross over), Week 4, 8, 16, 24, 28, 40, and 52 after cross-over
Secondary outcome [24] 0 0
Number of Participants Developing Thrombosis
Timepoint [24] 0 0
From randomization to Week 80 for BAT and Week 260 for Ruxolitinib

Eligibility
Key inclusion criteria
Confirmed diagnosis of PV according to the 2008 World Health Organization criteria,
Non-palpable spleen, Phlebotomy dependent, Resistant to or intolerant of hydroxyurea, ECOG
performance status of 0, 1 or 2.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Inadequate liver or renal function, Significant bacterial, fungal, parasitic, or viral
infection requiring treatment, Active malignancy within the past 5 years, excluding
specific skin cancers, Previously received treatment with a JAK inhibitor, Being treated
with any investigational agent, Women who are pregnant or nursing.

Other inclusion/exclusion criteria apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Novartis Investigative Site - Herston
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Antwerpen
Country [2] 0 0
Belgium
State/province [2] 0 0
Leuven
Country [3] 0 0
Canada
State/province [3] 0 0
Ontario
Country [4] 0 0
France
State/province [4] 0 0
Bayonne Cedex
Country [5] 0 0
France
State/province [5] 0 0
Bordeaux
Country [6] 0 0
France
State/province [6] 0 0
Brest
Country [7] 0 0
France
State/province [7] 0 0
Lille cedex
Country [8] 0 0
France
State/province [8] 0 0
Nice Cedex
Country [9] 0 0
France
State/province [9] 0 0
Paris
Country [10] 0 0
France
State/province [10] 0 0
Toulouse
Country [11] 0 0
Germany
State/province [11] 0 0
Baden-Wuerttemberg
Country [12] 0 0
Germany
State/province [12] 0 0
Augsburg
Country [13] 0 0
Germany
State/province [13] 0 0
Dresden
Country [14] 0 0
Germany
State/province [14] 0 0
Jena
Country [15] 0 0
Germany
State/province [15] 0 0
Leipzig
Country [16] 0 0
Germany
State/province [16] 0 0
Magdeburg
Country [17] 0 0
Germany
State/province [17] 0 0
Mainz
Country [18] 0 0
Germany
State/province [18] 0 0
Minden
Country [19] 0 0
Germany
State/province [19] 0 0
Ulm
Country [20] 0 0
Hungary
State/province [20] 0 0
Budapest
Country [21] 0 0
Hungary
State/province [21] 0 0
Debrecen
Country [22] 0 0
Hungary
State/province [22] 0 0
Kaposvar
Country [23] 0 0
India
State/province [23] 0 0
Maharashtra
Country [24] 0 0
India
State/province [24] 0 0
Tamil Nadu
Country [25] 0 0
Israel
State/province [25] 0 0
Nahariya
Country [26] 0 0
Israel
State/province [26] 0 0
Netanya
Country [27] 0 0
Israel
State/province [27] 0 0
Tel Aviv
Country [28] 0 0
Italy
State/province [28] 0 0
BO
Country [29] 0 0
Italy
State/province [29] 0 0
FI
Country [30] 0 0
Italy
State/province [30] 0 0
Lazio
Country [31] 0 0
Italy
State/province [31] 0 0
MI
Country [32] 0 0
Italy
State/province [32] 0 0
PV
Country [33] 0 0
Italy
State/province [33] 0 0
TO
Country [34] 0 0
Italy
State/province [34] 0 0
VA
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Seoul
Country [36] 0 0
Spain
State/province [36] 0 0
Andalucia
Country [37] 0 0
Spain
State/province [37] 0 0
Castilla Y Leon
Country [38] 0 0
Spain
State/province [38] 0 0
Catalunya
Country [39] 0 0
Spain
State/province [39] 0 0
Comunidad Valenciana
Country [40] 0 0
Spain
State/province [40] 0 0
Galicia
Country [41] 0 0
Spain
State/province [41] 0 0
Las Palmas De G.C
Country [42] 0 0
Spain
State/province [42] 0 0
Navarra
Country [43] 0 0
Spain
State/province [43] 0 0
Madrid
Country [44] 0 0
Turkey
State/province [44] 0 0
Izmir
Country [45] 0 0
Turkey
State/province [45] 0 0
Talas / Kayseri

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study compared the efficacy and safety of ruxolitinib to Best Available Therapy (BAT) in
patients with polycythemia vera (PV) who were hydroxyurea (HU) resistant or intolerant and
did not have a palpable spleen.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02038036
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02038036