NCT02038036

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 Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
149

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Mar 2014

Longer than P75 for phase_3

Geographic Reach
12 countries

48 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 14, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

January 16, 2014

Completed
2 months until next milestone

Study Start

First participant enrolled

March 25, 2014

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 29, 2015

Completed
4.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

April 7, 2020

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

July 20, 2021

Completed
Last Updated

July 20, 2021

Status Verified

June 1, 2021

Enrollment Period

1.5 years

First QC Date

January 14, 2014

Results QC Date

April 6, 2021

Last Update Submit

June 29, 2021

Conditions

Polycythemia Vera

Keywords

Polycythemia VeraHematologic DiseasesMyeloproliferative DisordersBone Marrow DiseasesHydroxyureaINC424Ruxolitinib

Outcome Measures

Primary Outcomes (1)

  • 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.

    Week 28

Secondary Outcomes (24)

  • Number of Participants Achieving a Complete Hematological Remission at Week 28

    Week 28

  • Number of Participants Achieving a Hematocrit (Hct) Control at Week 52 and Week 80

    Week 52 and 80

  • Number of Participants Achieving a Complete Hematological Remission at Week 52 and Week 80

    Week 52 and 80

  • Number of Participants With Phlebotomies Over Time

    Baseline to Week 260

  • Change From Baseline in Hematocrit (Hct) at Each Visit

    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

  • +19 more secondary outcomes

Study Arms (2)

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.

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.

Drug: Best Available Therapy

Interventions

Best Available TherapyDRUG

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.

Also known as: BAT
Best Available Therapy (BAT)
RuxolitinibDRUG

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.

Also known as: INC424
Ruxolitinib

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (48)

Novartis Investigative Site

Herston, Queensland, 4029, Australia

Location

Novartis Investigative Site

Antwerp, 2060, Belgium

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Toronto, Ontario, M4N 3M5, Canada

Location

Novartis Investigative Site

Bayonne, Bayonne Cedex, 64109, France

Location

Novartis Investigative Site

Bordeaux, 33076, France

Location

Novartis Investigative Site

Brest, 29200, France

Location

Novartis Investigative Site

Lille, 59020, France

Location

Novartis Investigative Site

Nice, 06202, France

Location

Novartis Investigative Site

Paris, 75010, France

Location

Novartis Investigative Site

Toulouse, 31059, France

Location

Novartis Investigative Site

Mannheim, Baden-Wurttemberg, 68305, Germany

Location

Novartis Investigative Site

Augsburg, 86150, Germany

Location

Novartis Investigative Site

Dresden, 01307, Germany

Location

Novartis Investigative Site

Jena, 07740, Germany

Location

Novartis Investigative Site

Leipzig, 04103, Germany

Location

Novartis Investigative Site

Magdeburg, 39120, Germany

Location

Novartis Investigative Site

Mainz, 55131, Germany

Location

Novartis Investigative Site

Minden, 32429, Germany

Location

Novartis Investigative Site

Ulm, 89081, Germany

Location

Novartis Investigative Site

Budapest, 1085, Hungary

Location

Novartis Investigative Site

Debrecen, 4032, Hungary

Location

Novartis Investigative Site

Kaposvár, 7400, Hungary

Location

Novartis Investigative Site

Mumbai, Maharashtra, 400012, India

Location

Novartis Investigative Site

Vellore, Tamil Nadu, 632 004, India

Location

Novartis Investigative Site

Nahariya, 22100, Israel

Location

Novartis Investigative Site

Netanya, 42150, Israel

Location

Novartis Investigative Site

Tel Aviv, 6423906, Israel

Location

Novartis Investigative Site

Bologna, BO, 40138, Italy

Location

Novartis Investigative Site

Florence, FI, 50134, Italy

Location

Novartis Investigative Site

Rome, Lazio, 00168, Italy

Location

Novartis Investigative Site

Milan, MI, 20122, Italy

Location

Novartis Investigative Site

Pavia, PV, 27100, Italy

Location

Novartis Investigative Site

Torino, TO, 10126, Italy

Location

Novartis Investigative Site

Varese, VA, 21100, Italy

Location

Novartis Investigative Site

Seoul, 03080, South Korea

Location

Novartis Investigative Site

Seoul, 03722, South Korea

Location

Novartis Investigative Site

Málaga, Andalusia, 29010, Spain

Location

Novartis Investigative Site

Salamanca, Castille and León, 37007, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

A Coruña, Galicia, 15006, Spain

Location

Novartis Investigative Site

Las Palmas de Gran Canaria, Las Palmas de G.C, 35010, Spain

Location

Novartis Investigative Site

Pamplona, Navarre, 31008, Spain

Location

Novartis Investigative Site

Alicante, Valencia, 03010, Spain

Location

Novartis Investigative Site

Madrid, 28034, Spain

Location

Novartis Investigative Site

Madrid, 28046, Spain

Location

Novartis Investigative Site

Izmir, 35040, Turkey (Türkiye)

Location

Novartis Investigative Site

Talas / Kayseri, 38039, Turkey (Türkiye)

Location

Related Publications (3)

  • 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.

    PMID: 35597252DERIVED

  • 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.

    PMID: 29396713DERIVED

  • 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.

    PMID: 27916398DERIVED

MeSH Terms

Conditions

Polycythemia VeraHematologic DiseasesMyeloproliferative DisordersBone Marrow Diseases

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Bone Marrow NeoplasmsHematologic NeoplasmsNeoplasms by SiteNeoplasmsHemic and Lymphatic Diseases

Results Point of Contact

Title
Study Director
Organization
Novartis Pharmaceuticals
Novartis.email@novartis.com
862-778-8300

Study Officials

  • Novartis Pharmaceuticals

    Novartis Pharmaceuticals

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 14, 2014

First Posted

January 16, 2014

Study Start

March 25, 2014

Primary Completion

September 29, 2015

Study Completion

April 7, 2020

Last Updated

July 20, 2021

Results First Posted

July 20, 2021

Record last verified: 2021-06

Data Sharing

IPD Sharing
Will share

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

Locations

IN(2)CA(1)KR(2)IT(7)BE(2)TU(2)ES(9)AU(1)FR(7)IL(3)DE(9)HU(3)