Ruxolitinib Efficacy and Safety in Patients With HU Resistant or Intolerant Polycythemia Vera vs Best Available Therapy.

NCT ID: NCT02038036

Last Updated: 2021-07-20

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

149 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-03-25

Study Completion Date

2020-04-07

Brief Summary

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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

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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

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Polycythemia Vera

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Ruxolitinib

Intervention Type DRUG

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.

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.

Group Type ACTIVE_COMPARATOR

Best Available Therapy

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

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 Type DRUG

Other Intervention Names

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BAT INC424

Eligibility Criteria

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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.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Novartis Investigative Site

Herston, Queensland, Australia

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Antwerp, , Belgium

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Leuven, , Belgium

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Toronto, Ontario, Canada

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Bayonne, Bayonne Cedex, France

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Bordeaux, , France

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Brest, , France

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Lille, , France

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Nice, , France

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Paris, , France

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Toulouse, , France

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Mannheim, Baden-Wurttemberg, Germany

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Augsburg, , Germany

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Dresden, , Germany

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Jena, , Germany

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Leipzig, , Germany

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Magdeburg, , Germany

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Mainz, , Germany

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Minden, , Germany

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Ulm, , Germany

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Budapest, , Hungary

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Debrecen, , Hungary

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Kaposvár, , Hungary

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Mumbai, Maharashtra, India

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Vellore, Tamil Nadu, India

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Nahariya, , Israel

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Netanya, , Israel

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Tel Aviv, , Israel

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Bologna, BO, Italy

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Florence, FI, Italy

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Rome, Lazio, Italy

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Milan, MI, Italy

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Pavia, PV, Italy

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Torino, TO, Italy

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Varese, VA, Italy

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Seoul, , South Korea

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Seoul, , South Korea

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Málaga, Andalusia, Spain

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Salamanca, Castille and León, Spain

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Barcelona, Catalonia, Spain

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A Coruña, Galicia, Spain

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Las Palmas de Gran Canaria, Las Palmas de G.C, Spain

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Pamplona, Navarre, Spain

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Alicante, Valencia, Spain

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Madrid, , Spain

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Madrid, , Spain

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Izmir, , Turkey (Türkiye)

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Novartis Investigative Site

Talas / Kayseri, , Turkey (Türkiye)

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Countries

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Australia Belgium Canada France Germany Hungary India Israel Italy South Korea Spain Turkey (Türkiye)

References

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Passamonti 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.

Reference Type DERIVED
PMID: 35597252 (View on PubMed)

Kiladjian 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.

Reference Type DERIVED
PMID: 29396713 (View on PubMed)

Passamonti 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.

Reference Type DERIVED
PMID: 27916398 (View on PubMed)

Other Identifiers

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CINC424B2401

Identifier Type: -

Identifier Source: org_study_id

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