Polycythemia VeraPhase 3RESPONSE-2NCT02038036
Ruxolitinib Efficacy and Safety in Patients With HU Resistant or Intolerant Polycythemia Vera vs Best Available Therapy.
A Phase 3 study testing Best Available Therapy and Ruxolitinib in people with Polycythemia Vera, run by Novartis Pharmaceuticals at 48 sites in 12 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Polycythemia Vera
- What is being tested?
- Best Available Therapy and Ruxolitinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 149 participants
- Where
- 48 sitesin 12 countries
- Study dates
- 25 Mar 2014to 7 Apr 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
48 sites in 12 countries.
48 sites in 12 countries
Germany9 sites
Novartis Investigative Site
Augsburg, 86150
Novartis Investigative Site
Dresden, 01307
Novartis Investigative Site
Jena, 07740
Novartis Investigative Site
Leipzig, 04103
Novartis Investigative Site
Magdeburg, 39120
Novartis Investigative Site
Mainz, 55131
Novartis Investigative Site
Mannheim, Baden-Wurttemberg, 68305
Novartis Investigative Site
Minden, 32429
Novartis Investigative Site
Ulm, 89081
Spain9 sites
Novartis Investigative Site
A Coruña, Galicia, 15006
Novartis Investigative Site
Alicante, Valencia, 03010
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Las Palmas de Gran Canaria, Las Palmas de G.C, 35010
Novartis Investigative Site
Madrid, 28034
Novartis Investigative Site
Madrid, 28046
Novartis Investigative Site
Málaga, Andalusia, 29010
Novartis Investigative Site
Pamplona, Navarre, 31008
Novartis Investigative Site
Salamanca, Castille and León, 37007
France7 sites
Novartis Investigative Site
Bayonne, Bayonne Cedex, 64109
Novartis Investigative Site
Bordeaux, 33076
Novartis Investigative Site
Brest, 29200
Novartis Investigative Site
Lille, 59020
Novartis Investigative Site
Nice, 06202
Novartis Investigative Site
Paris, 75010
Novartis Investigative Site
Toulouse, 31059
Italy7 sites
Novartis Investigative Site
Bologna, BO, 40138
Novartis Investigative Site
Florence, FI, 50134
Novartis Investigative Site
Milan, MI, 20122
Novartis Investigative Site
Pavia, PV, 27100
Novartis Investigative Site
Rome, Lazio, 00168
Novartis Investigative Site
Torino, TO, 10126
Novartis Investigative Site
Varese, VA, 21100
Hungary3 sites
Novartis Investigative Site
Budapest, 1085
Novartis Investigative Site
Debrecen, 4032
Novartis Investigative Site
Kaposvár, 7400
Israel3 sites
Novartis Investigative Site
Nahariya, 22100
Novartis Investigative Site
Netanya, 42150
Novartis Investigative Site
Tel Aviv, 6423906
Belgium2 sites
Novartis Investigative Site
Antwerp, 2060
Novartis Investigative Site
Leuven, 3000
India2 sites
Novartis Investigative Site
Mumbai, Maharashtra, 400012
Novartis Investigative Site
Vellore, Tamil Nadu, 632 004
South Korea2 sites
Novartis Investigative Site
Seoul, 03080
Novartis Investigative Site
Seoul, 03722
Turkey (Türkiye)2 sites
Novartis Investigative Site
Izmir, 35040
Novartis Investigative Site
Talas / Kayseri, 38039
About this study
Official 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)
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.
Read the detailed description
This was a prospective, multi-center, open-label, randomized, Phase IIIb study evaluating efficacy and safety of ruxolitinib versus BAT as selected by the Investigator in patients with PV who are resistant to, or intolerant of HU.
The study comprised of the following periods:
Screening Period (up to 5 weeks: Day -35 to Day -1): Screening evaluations were performed at one or more clinic visits, and reviewed to determine eligibility before the patient was randomized in the study.
Core Treatment Period (Day 1 to Week 80):
Patients were randomized in 1:1 ratio to either treatment group (ruxolitinib or BAT) and were to be treated with their randomized treatment.
Crossover Treatment Period (Week 28 or after) for BAT patients only:
Patients randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib. Patients crossing over on or after Week 28 had to complete all assessments for the End of Treatment (EoT) visit of the Core Treatment Period followed by the assessments in Cross-over visit evaluation schedule.
Extended Treatment Period (Week 80 to Week 260):
Patients receiving ruxolitinib at Week 80 (including patients who have crossed over from BAT) were eligible to continue up to Week 260 in the Extended Treatment Period. Patients continued the ruxolitinib dose that they received at Week 80. Patients who received BAT at Week 80 were not eligible to enter the Extended Treatment Period and had to have the EoT visit at Week 80 and an End of study (EoS) visit 30 days after the EoT visit.
Follow-up Period:
Patients were followed for safety during 30 days after the last dose of study drug and EoS visit assessments were performed post 30 days after the last dose of study drug. Patients who completed EoT (Week 80 for patients who received BAT, Week 260 for patients who received ruxolitinib or from the time of premature discontinuation) were to be followed-up for every 3 months for survival till the end of the study.
- Conditions
- Polycythemia Vera
- Being tested
- Best Available Therapy, Ruxolitinib
- Keywords
- Polycythemia Vera, Hematologic Diseases, Myeloproliferative Disorders, Bone Marrow Diseases, Hydroxyurea, INC424, Ruxolitinib
- Medical subject headings
- Polycythemia Vera, Hematologic Diseases, Myeloproliferative Disorders, Bone Marrow Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Best Available TherapyDrug
Also called 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.
RuxolitinibDrug
Also called INC424
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.
| Study group | Role | What they receive |
|---|---|---|
| Ruxolitinib | Experimental | 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. Receives: Drug: Ruxolitinib |
| Best Available Therapy (BAT) | Active comparator | 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. Receives: Drug: Best Available Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Achieving Hematocrit (Hct) Control at Week 28
Proportion of patients achieving Hct control at Week 28 was defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 28, with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8.
Phlebotomy eligibility was defined by:
- Confirmed Hct > 45% that is at least 3 percentage points higher than the Hct obtained at Baseline Or
- Confirmed Hct > 48% The confirmation occurred 2 to 14 days subsequent to the initial observation.
Measured: Week 28
Secondary outcomes (24)
Number of Participants Achieving a Complete Hematological Remission at Week 28
Proportion of patients achieving a complete hematological remission at Week 28 was defined by:
- Hct control at Week 28 defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 28, with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8, and
- WBC < 10 x109/L at Week 28, and
- Platelets ≤ 400 x 109/L at Week 28
Measured: Week 28
Number of Participants Achieving a Hematocrit (Hct) Control at Week 52 and Week 80
Proportion of patients achieving a Hct control at Week 52 was defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 52, and no more than one phlebotomy eligibility occurring post randomization and prior to Week 8
- Endpoint for Week 80 was defined, similarly.
Measured: Week 52 and 80
Number of Participants Achieving a Complete Hematological Remission at Week 52 and Week 80
Proportion of patients achieving a complete hematological remission at Week 52, was defined by:
- Hct control at Week 52, as defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 52 with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8, and
- White Blood Count (WBC) < 10 x10^9/L at Week 52, and
- Platelets ≤ 400 x 10^9/L at Week 52
- Endpoint for Week 80 was defined, similarly.
Measured: Week 52 and 80
Number of Participants With Phlebotomies Over Time
Phlebotomy eligibility was defined by Confirmed Hct > 45% that is at least 3 percentage points higher than the Hct obtained at Baseline Or Confirmed Hct > 48%. The confirmation occurred 2 to 14 days subsequent to the initial observation.
Measured: Baseline to Week 260
Change From Baseline in Hematocrit (Hct) at Each Visit
Hematocrit is the volume percentage of red blood cells (RBC) in the blood.
Measured: 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
Change From Baseline in Hematocrit (Hct) at Each Scheduled Visit After Crossover in Participants Randomized to BAT Who Cross Over to Ruxolitinib
Hematocrit is the percentage of red blood cells (RBC) in the blood.
Measured: 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
Spleen Length by Visit
Spleen length was assessed by manual palpation at every study visit.
Measured: 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
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status to Week 28
The ECOG scale of performance status described the level of functioning of participants in terms of their ability to care for themselves, daily activity, and physical ability. The ECOG performance was recorded as per ECOG performance status grades ranging from 0 (fully active, able to carry on all pre-disease performance without restriction) to 5 (dead).
Measured: Baseline and Week 28
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
Proportion of patients achieving a partial remission at Week 28, based on the ELN and IWG-MRT criteria, as defined by:
- Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) score reduction of greater than or equal to 10 points from baseline to Week 28, and
- Hct control defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 28, with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8, and
- WBC < 10 x10^9/L at Week 28, and
- Platelets ≤ 400 x 10^9/L at Week 28, and
- No palpable spleen at Week 28, and
- No hemorrhagic or thrombotic events, and
- No transformation into post-PV myelofibrosis, myelodysplastic syndrome (IWG-MRT criteria) or acute leukemia (WHO criteria).
Measured: Week 28
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
Proportion of patients who achieved partial remission at Week 52 based on the ELN and IWG-MRT criteria, as defined by:
- MPN-SAF TSS score reduction of greater than or equal to 10 points from baseline to Week 52 and
- Hct control defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 52 with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8, and
- WBC < 10 x109/L at Week 52 and
- Platelets ≤ 400 x 109/L at Week 52 and
- No palpable spleen at Week 52 and
- No hemorrhagic or thrombotic events, and
- No transformation into post-PV myelofibrosis, myelodysplastic syndrome (IWG-MRT criteria) or acute leukemia (WHO criteria).
- Endpoint for Week 80 was defined, similarly.
Measured: Week 52 and 80
Number of Participants Achieving a Hematocrit (Hct) Control at Week 104, Week 156, Week 208 and Week 260.
Proportion of patients achieving a Hct control at Week 104 as defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 104 and with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8 Endpoint for Week 156, Week 208 and Week 260 were defined, similarly.
Measured: From Week 8 to Week 104, 156, 208 and 260
Number of Participants Achieving a Complete Hematological Remission at Week 104, Week 156, Week 208 and Week 260
Proportion of patients achieving a complete hematological remission at Week 104 as defined by Hct control defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 104, with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8, and
- WBC < 10 x10^9/L at Week 104, and
- Platelets ≤ 400 x 10^9/L at Week 104 Endpoint for Week 156, Week 208 and Week 260 were defined, similarly.
Measured: From Week 8 to Week 104, 156, 208 and 260
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.
Proportion of patients who achieved partial remission at Week 104, based on the ELN and IWG-MRT criteria, as defined by:
- MPN-SAF TSS score reduction of greater than or equal to 10 points from baseline to Week 104, and
- Hct control defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 104, with no more than one phlebotomy eligibility occurring post-randomization and prior to Week 8, and
- WBC < 10 x10^9/L at Week 104, and
- Platelets ≤ 400 x 10^9/L at Week 104, and
- No palpable spleen at Week 104, and
- No hemorrhagic or thrombotic events, and
- No transformation into post-PV myelofibrosis, myelodysplastic syndrome (IWG-MRT criteria) or acute leukemia (WHO criteria) Endpoint for Week 156, Week 208 and Week 260 are defined, similarly.
Measured: From Week 8 to Week 104, 156, 208 and 260
Number of Participants With Transformation Free Survival Events
Transformation-free survival is defined as one of the following:
- Myelofibrosis (MF) as evidenced by bone marrow biopsy, or
- Acute leukemia as evidenced by bone marrow blast counts of at least 20%, or peripheral blast counts of at least 20% lasting at least 2 weeks.
- Death due to any cause during treatment period
Measured: Week 260 (ruxolitinib arm) and Week 80 (BAT arm)
Number of Participants With Overall Survival (OS) Events
Overall survival (OS) event is defined as death due to any cause. OS events were counted in the BAT arm, irrespective of whether participants crossed over to receive ruxolitinib when the event occurred.
Measured: up to Week 260
Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)
The MPN-SAF TSS is 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. Each item is scored on a scale ranging from 0 (no fatigue/absent) to 10 (As bad as you can imagine/worst imaginable).The MPN-SAF TSS is computed as the average of the observed items multiplied by 10 to achieve a 0-to-100 scale. The MPN-SAF TSS thus has a possible score range of 0 to 100 where a decrease indicates improvement.
Measured: Baseline, Week 4, 8, 16, 28, 40, 52, 80, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234 and 247
Change From Baseline in Total Scores of MPN-SAF by Visit in Patients From BAT Group Who Cross Over to Ruxolitinib After Crossover
The MPN-SAF TSS is 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. Each item is scored on a scale ranging from 0 (no fatigue/absent) to 10 (As bad as you can imagine/worst imaginable).The MPN-SAF TSS is computed as the average of the observed items multiplied by 10 to achieve a 0-to-100 scale. The MPN-SAF TSS thus has a possible score range of 0 to 100 where a decrease indicates improvement.
Measured: 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
Change From Baseline in Score as Per European Quality of Life 5-Dimension 5-level (EQ-5D-5L) Questionnaire
EQ-5D-5L is a standardized instrument for measuring health outcomes in a wide range of health conditions and treatments. It consists of visual analogue scale (EQ VAS) which records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labeled 'Best imaginable health state' and 'worst imaginable health state'. The EQ VAS scores were anchored on 100 = the best health you can imagine and 0 = worst health you can imagine.
Measured: Baseline, Week 4, 8, 16, 28, 52, 80, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234 and 247
Change From Baseline in EQ-5D-5L VAS, by Visit in Patients From BAT Group Who Cross Over to Ruxolitinib After Crossover
EQ-5D-5L is a standardized instrument for measuring health outcomes in a wide range of health conditions and treatments. It consists of visual analogue scale (EQ VAS) which records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labeled 'Best imaginable health state' and 'worst imaginable health state'. The EQ VAS scores were anchored on 100 = the best health you can imagine and 0 = worst health you can imagine.
Measured: 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
Change From Baseline in Work Productivity and Activity Impairment (WPAI) Questionnaire
The Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) is a six item questionnaire which intended to measure work and activity impairment associated with polycythemia vera. WPAI consisted of 6 questions (Q1=Employment status; Q2=Hours absent from work due to the polycythemia vera; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the polycythemia vera on productivity while working; Q6=Impact of the polycythemia vera on productivity while doing regular daily activities other than work). Higher WPAI scores indicated greater activity impairment. Scores were multiplied by 100 to express in percentages.
Percent work time missed due to problem (past 7 days) =Q2/(Q2+Q4) Percent impairment while working due to problem (past 7 days): Q5/10 Percent overall work impairment due to problem (past 7 says): Q2/(Q2+Q4)+[(1 Q2/(Q2+Q4))x(Q5/10)] Percent activity impairment due to problem (past 7 says): Q6/10
Measured: Baseline, Week 4, 8, 16, 28, 52 and 80
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
The Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) is a six item questionnaire which intended to measure work and activity impairment associated with polycythemia vera. WPAI consisted of 6 questions (Q1=Employment status; Q2=Hours absent from work due to the polycythemia vera; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the polycythemia vera on productivity while working; Q6=Impact of the polycythemia vera on productivity while doing regular daily activities other than work). Higher WPAI scores indicated greater activity impairment. Scores were multiplied by 100 to express in percentages.
Percent work time missed due to problem (past 7 days) =Q2/(Q2+Q4) Percent impairment while working due to problem (past 7 days): Q5/10 Percent overall work impairment due to problem (past 7 says): Q2/(Q2+Q4)+[(1 Q2/(Q2+Q4))x(Q5/10)] Percent activity impairment due to problem (past 7 says): Q6/10
Measured: Baseline (last assessment before cross over), Week 4, 8, 16, 24, 28 and 52 after cross-over
Patient Global Impression of Change (PGIC)
The Patient Global Impression of Change (PGIC) is comprised of a single question intended to measure a patient's perspective of improvement or deterioration over time relative to treatment. The PGIC uses a seven-point scale where one (1) equals very much improved and seven (7) equals very much worse.
Measured: Week 4, 8, 16, 28, 40, 52 and 80
Summary of Patient Global Impression of Change (PGIC), by Visit in Patients From BAT Group Who Cross Over to Ruxolitinib After Crossover
The Patient Global Impression of Change (PGIC) is comprised of a single question intended to measure a patient's perspective of improvement or deterioration over time relative to treatment. The PGIC uses a seven-point scale where one (1) equals very much improved and seven (7) equals very much worse.
Measured: Baseline (last assessment before cross over), Week 4, 8, 16, 24, 28, 40, and 52 after cross-over
Number of Participants Developing Thrombosis
Proportion of participants developing any arterial or venous thromboembolic event
Measured: From randomization to Week 80 for BAT and Week 260 for Ruxolitinib
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2014 (estimated)
- Study start25 Mar 2014
- Primary completion29 Sep 2015
- Study completion7 Apr 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Polycythemia VeraStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 149 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02038036
- Sponsor's protocol ID
- CINC424B2401
- Acronym
- RESPONSE-2
- Status last verified
- Jun 2021
- First submitted
- 14 Jan 2014
- Last updated
- 20 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Publications
Harrison CN, Kiladjian JJ, Hamer-Maansson JE, Naim A, Palandri F, Passamonti F. Ruxolitinib treatment in patients with polycythemia vera reduces JAK2 variant allele frequency and improves symptom burden and hematocrit control. Ther Adv Hematol. 2026 Mar 24;17:20406207261425083. doi: 10.1177/20406207261425083. eCollection 2026.
PubMed 41890273Passamonti F, Palandri F, Saydam G, Callum J, Devos T, Guglielmelli P, Vannucchi AM, Zor E, Zuurman M, Gilotti G, Zhang Y, Griesshammer M. Ruxolitinib versus best available therapy in inadequately controlled polycythaemia vera without splenomegaly (RESPONSE-2): 5-year follow up of a randomised, phase 3b study. Lancet Haematol. 2022 Jul;9(7):e480-e492. doi: 10.1016/S2352-3026(22)00102-8. Epub 2022 May 18.
PubMed 35597252Kiladjian JJ, Guglielmelli P, Griesshammer M, Saydam G, Masszi T, Durrant S, Passamonti F, Jones M, Zhen H, Li J, Gadbaw B, Perez Ronco J, Khan M, Verstovsek S. Efficacy and safety of ruxolitinib after and versus interferon use in the RESPONSE studies. Ann Hematol. 2018 Apr;97(4):617-627. doi: 10.1007/s00277-017-3225-1. Epub 2018 Feb 2.
PubMed 29396713Passamonti F, Griesshammer M, Palandri F, Egyed M, Benevolo G, Devos T, Callum J, Vannucchi AM, Sivgin S, Bensasson C, Khan M, Mounedji N, Saydam G. Ruxolitinib for the treatment of inadequately controlled polycythaemia vera without splenomegaly (RESPONSE-2): a randomised, open-label, phase 3b study. Lancet Oncol. 2017 Jan;18(1):88-99. doi: 10.1016/S1470-2045(16)30558-7. Epub 2016 Dec 2.
PubMed 27916398
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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)
- ClinicalTrials.gov ID
- NCT02038036
- Acronym / sponsor ID
- RESPONSE-2 / CINC424B2401
- Conditions
- Polycythemia Vera
- Keywords
- Polycythemia Vera, Hematologic Diseases, Myeloproliferative Disorders, Bone Marrow Diseases, Hydroxyurea, INC424, Ruxolitinib
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 149 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 25 Mar 2014 (actual)
- Primary completion
- 29 Sep 2015 (actual)
- Study completion
- 7 Apr 2020 (actual)
- First posted
- 16 Jan 2014 (estimated)
- Results
- Posted 20 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This was a prospective, multi-center, open-label, randomized, Phase IIIb study evaluating efficacy and safety of ruxolitinib versus BAT as selected by the Investigator in patients with PV who are resistant to, or intolerant of HU.
The study comprised of the following periods:
Screening Period (up to 5 weeks: Day -35 to Day -1): Screening evaluations were performed at one or more clinic visits, and reviewed to determine eligibility before the patient was randomized in the study.
Core Treatment Period (Day 1 to Week 80):
Patients were randomized in 1:1 ratio to either treatment group (ruxolitinib or BAT) and were to be treated with their randomized treatment.
Crossover Treatment Period (Week 28 or after) for BAT patients only:
Patients randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib. Patients crossing over on or after Week 28 had to complete all assessments for the End of Treatment (EoT) visit of the Core Treatment Period followed by the assessments in Cross-over visit evaluation schedule.
Extended Treatment Period (Week 80 to Week 260):
Patients receiving ruxolitinib at Week 80 (including patients who have crossed over from BAT) were eligible to continue up to Week 260 in the Extended Treatment Period. Patients continued the ruxolitinib dose that they received at Week 80. Patients who received BAT at Week 80 were not eligible to enter the Extended Treatment Period and had to have the EoT visit at Week 80 and an End of study (EoS) visit 30 days after the EoT visit.
Follow-up Period:
Patients were followed for safety during 30 days after the last dose of study drug and EoS visit assessments were performed post 30 days after the last dose of study drug. Patients who completed EoT (Week 80 for patients who received BAT, Week 260 for patients who received ruxolitinib or from the time of premature discontinuation) were to be followed-up for every 3 months for survival till the end of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ruxolitinib | Experimental | Drug: RuxolitinibRuxolitinib 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. |
| Best Available Therapy (BAT) | Active comparator | Drug: Best Available TherapyBest 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Best Available TherapyAlso: BATBest 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. | Drug | Best Available Therapy (BAT) |
| RuxolitinibAlso: INC424Ruxolitinib 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. | Drug | Ruxolitinib |
Primary outcome
Number of Participants Achieving Hematocrit (Hct) Control at Week 28
Time frame: Week 28
Proportion of patients achieving Hct control at Week 28 was defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 28, with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8. Phlebotomy eligibility was defined by: * Confirmed Hct > 45% that is at least 3 percentage points higher than the Hct obtained at Baseline Or * Confirmed Hct > 48% The confirmation occurred 2 to 14 days subsequent to the initial observation.
24 secondary outcomes
Number of Participants Achieving a Complete Hematological Remission at Week 28
Time frame: Week 28
Number of Participants Achieving a Hematocrit (Hct) Control at Week 52 and Week 80
Time frame: Week 52 and 80
Number of Participants Achieving a Complete Hematological Remission at Week 52 and Week 80
Time frame: Week 52 and 80
Number of Participants With Phlebotomies Over Time
Time frame: Baseline to Week 260
Change From Baseline in Hematocrit (Hct) at Each Visit
Time frame: 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
Change From Baseline in Hematocrit (Hct) at Each Scheduled Visit After Crossover in Participants Randomized to BAT Who Cross Over to Ruxolitinib
Time frame: 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
Spleen Length by Visit
Time frame: 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
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status to Week 28
Time frame: Baseline and Week 28
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
Time frame: Week 28
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
Time frame: Week 52 and 80
Number of Participants Achieving a Hematocrit (Hct) Control at Week 104, Week 156, Week 208 and Week 260.
Time frame: From Week 8 to Week 104, 156, 208 and 260
Number of Participants Achieving a Complete Hematological Remission at Week 104, Week 156, Week 208 and Week 260
Time frame: From Week 8 to Week 104, 156, 208 and 260
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.
Time frame: From Week 8 to Week 104, 156, 208 and 260
Number of Participants With Transformation Free Survival Events
Time frame: Week 260 (ruxolitinib arm) and Week 80 (BAT arm)
Number of Participants With Overall Survival (OS) Events
Time frame: up to Week 260
Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)
Time frame: Baseline, Week 4, 8, 16, 28, 40, 52, 80, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234 and 247
Change From Baseline in Total Scores of MPN-SAF by Visit in Patients From BAT Group Who Cross Over to Ruxolitinib After Crossover
Time frame: 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
Change From Baseline in Score as Per European Quality of Life 5-Dimension 5-level (EQ-5D-5L) Questionnaire
Time frame: Baseline, Week 4, 8, 16, 28, 52, 80, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234 and 247
Change From Baseline in EQ-5D-5L VAS, by Visit in Patients From BAT Group Who Cross Over to Ruxolitinib After Crossover
Time frame: 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
Change From Baseline in Work Productivity and Activity Impairment (WPAI) Questionnaire
Time frame: Baseline, Week 4, 8, 16, 28, 52 and 80
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
Time frame: Baseline (last assessment before cross over), Week 4, 8, 16, 24, 28 and 52 after cross-over
Patient Global Impression of Change (PGIC)
Time frame: Week 4, 8, 16, 28, 40, 52 and 80
Summary of Patient Global Impression of Change (PGIC), by Visit in Patients From BAT Group Who Cross Over to Ruxolitinib After Crossover
Time frame: Baseline (last assessment before cross over), Week 4, 8, 16, 24, 28, 40, and 52 after cross-over
Number of Participants Developing Thrombosis
Time frame: From randomization to Week 80 for BAT and Week 260 for Ruxolitinib
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41890273Harrison CN, Kiladjian JJ, Hamer-Maansson JE, Naim A, Palandri F, Passamonti F. Ruxolitinib treatment in patients with polycythemia vera reduces JAK2 variant allele frequency and improves symptom burden and hematocrit control. Ther Adv Hematol. 2026 Mar 24;17:20406207261425083. doi: 10.1177/20406207261425083. eCollection 2026.
- Derived from this study: PubMed 35597252Passamonti F, Palandri F, Saydam G, Callum J, Devos T, Guglielmelli P, Vannucchi AM, Zor E, Zuurman M, Gilotti G, Zhang Y, Griesshammer M. Ruxolitinib versus best available therapy in inadequately controlled polycythaemia vera without splenomegaly (RESPONSE-2): 5-year follow up of a randomised, phase 3b study. Lancet Haematol. 2022 Jul;9(7):e480-e492. doi: 10.1016/S2352-3026(22)00102-8. Epub 2022 May 18.
- Derived from this study: PubMed 29396713Kiladjian JJ, Guglielmelli P, Griesshammer M, Saydam G, Masszi T, Durrant S, Passamonti F, Jones M, Zhen H, Li J, Gadbaw B, Perez Ronco J, Khan M, Verstovsek S. Efficacy and safety of ruxolitinib after and versus interferon use in the RESPONSE studies. Ann Hematol. 2018 Apr;97(4):617-627. doi: 10.1007/s00277-017-3225-1. Epub 2018 Feb 2.
- Derived from this study: PubMed 27916398Passamonti F, Griesshammer M, Palandri F, Egyed M, Benevolo G, Devos T, Callum J, Vannucchi AM, Sivgin S, Bensasson C, Khan M, Mounedji N, Saydam G. Ruxolitinib for the treatment of inadequately controlled polycythaemia vera without splenomegaly (RESPONSE-2): a randomised, open-label, phase 3b study. Lancet Oncol. 2017 Jan;18(1):88-99. doi: 10.1016/S1470-2045(16)30558-7. Epub 2016 Dec 2.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
48 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Best Available Therapy and Ruxolitinib in people with Polycythemia Vera, run by Novartis Pharmaceuticals at 48 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 48 sites in Germany, Spain, France, Italy, Hungary and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Achieving Hematocrit (Hct) Control at Week 28 (time frame: Week 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02038036, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2021.