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Trial record 18 of 79 for:    INCB018424

Ruxolitinib Efficacy and Safety in Patients With HU Resistant or Intolerant Polycythemia Vera vs Best Available Therapy. (RESPONSE 2)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT02038036
First received: January 14, 2014
Last updated: November 3, 2014
Last verified: November 2014
  Purpose

This trial will compare the efficacy and safety of ruxolitinib to Best Available Therapy (BAT) in patients with polycythemia vera (PV) who are hyroxyurea (HU) resistant or intolerant and do not have a palpable spleen.


Condition Intervention Phase
Polycythemia Vera
Drug: Best Available Therapy
Drug: ruxolitinib
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Efficacy of ruxolitinib to Best Available Therapy (BAT) as assessed by Hct control at Week 28 [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
    Proportion of patients achieving Hct control at Week 28 as defined by: •Hct < 45% at Week 16 and maintained until Week 28, and •No phlebotomy from Week 4 to Week 28, with no more than one phlebotomy occurring post randomization and prior to the Week 4 visit.


Secondary Outcome Measures:
  • Efficacy of ruxolitinib to BAT as assessed by peripheral blood count remission at Week 28. [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
    Proportion of patients achieving a peripheral blood count remission at Week 28 as defined by: Hct < 45% at Week 16 and maintained until Week 28, and WBC < 10 x10E9/L at Week 16 and maintained until Week 28, and Platelets ≤ 400 x 10E9/L at Week 16 and maintained until Week 28, and No phlebotomy from Week 4 to Week 28, with no more than one phlebotomy occurring post randomization and prior to the Week 4 visit.

  • Efficacy of ruxolitinib to BAT as assessed by durable Hct control at Week 52 [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    Proportion of patients achieving a Hct control at Week 52 as defined by: Hct < 45% at Week 16 and maintained until Week 52, and no phlebotomy from Week 4 to Week 28, with no more than one phlebotomy occurring post randomization and prior to the Week 4 visit, and, in the BAT arm, no change in the treatment regimen or crossover to the ruxolitinib arm.

  • Efficacy of ruxolitinib to BAT as assessed by durable peripheral blood count remission at Week 52. [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    Proportion of patients achieving a peripheral blood count remission at Week 52 as defined by: •Hct < 45% at Week 16 and maintained until Week 52, and WBC < 10 x10E9/L at Week 16 and maintained until Week 52, and Platelets ≤ 400 x 10E9/L at Week 16 and maintained until Week 52, and, no phlebotomy from Week 4 to Week 52, with no more than one phlebotomy occurring post randomization and prior to the Week 4 visit, and in the BAT arm, no change in the treatment regimen or crossover to the ruxolitinib arm.

  • Change in ECOG status [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
    Change in ECOG status from baseline to Week 28

  • Change in spleen length [ Time Frame: Week 4, 8, 12, 16, 20, 24, 28, 40, 52/End of Treatment ] [ Designated as safety issue: No ]
    Change from Baseline in spleen length at each scheduled visit

  • Efficacy of ruxolitinib to BAT as assessed by partial remission based on the ELN and IWG-MRT criteria at Week 28 [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
    Proportion of patients achieving a partial remission at Week 28, 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 16 and maintained until Week 28 (for patients with a baseline score of 20 or more), and •Hct < 45% at Week 16 and maintained until Week 28, and •No phlebotomy from Week 4 to Week 28, with no more than one phlebotomy occurring post randomization and prior to the Week 4 visit, and •WBC < 10 x10E9/L at Week 16 and maintained until Week 28, and •Platelets ≤ 400 x 10E9/L at Week 16 and maintained until Week 28, and •No palpable spleen at Week 16 and maintained until Week 28, and •No hemorrhagic or thrombotic events, and •No transformation into post-PV myelofibrosis, myelodysplastic syndrome, or acute leukemia

  • Efficacy of ruxolitinib to BAT as assessed by durable partial remission based on the ELN and IWG-MRT criteria at Week 52. [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    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 16 and maintained until Week 52 (for patients with a baseline score of 20 or more), and •Hct < 45% at Week 16 and maintained until Week 52, and •No phlebotomy from Week 4 to Week 52, with no more than one phlebotomy occurring post randomization and prior to the Week 4 visit, and •WBC < 10 x10E9/L at Week 16 and maintained until Week 52, and •Platelets ≤ 400 x 10E9/L at Week 16 and maintained until Week 52, and •No palpable spleen at Week 16 and maintained until 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), and •In the BAT arm, no change in the treatment regimen or crossover to the ruxolitinib arm.

  • Efficacy of BAT patients after they cross over to ruxolitinib [ Time Frame: +4, +8, +12, +16, +20, +24 weeks after crossover ] [ Designated as safety issue: No ]
    Among patients randomized to BAT who cross over to ruxolitinib, proportion of patients achieving Hct < 45% at each visit after cross over

  • Changes in MPN-SAF TSS [ Time Frame: Week 4, 8, 16, 28, 40, 52/End of Treatment ] [ Designated as safety issue: No ]
    Proportion of patients achieving at least a 50% reduction from baseline in MPN-SAF TSS score at each visit where it is measured.

  • Resolution of disease related symptoms in MPN-SAF TSS at Week 28. [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
    Proportion of patients achieving a resolution of disease related symptoms in MPN-SAF TSS at Week 28 defined as: • MPN-SAF TSS score reduction of greater than or equal to 10 points from baseline to Week 16 and maintained until Week 28 (for patients with a baseline score of 20 or more).

  • Changes in patient reported outcomes [ Time Frame: Week 4, 8, 16, 28, 40, 52/End of Treatment ] [ Designated as safety issue: No ]

    Change in MPN-SAF TSS from baseline to each visit where measured.

    • PSIS at each visit where measured.
    • Change in EQ-5D-5L score from baseline to each visit where measured.
    • Change in WPAI from baseline to each visit where measured.
    • PGIC at each visit where measured.

  • Safety of ruxolitinib and Best Available Therapy [ Time Frame: Week 28, 52/EoT ] [ Designated as safety issue: Yes ]
    Safety will be assessed by monitoring the frequency, duration and severity of Adverse Events, and evaluating changes in vital signs, electrocardiograms (ECGs), serum chemistry, hematology and urinalysis results.

  • Safety of BAT patients after they crossover [ Time Frame: +52/EoT ] [ Designated as safety issue: Yes ]
    Safety will be assessed by monitoring the frequency, duration and severity of Adverse Events, and evaluating changes in vital signs, electrocardiograms (ECGs), serum chemistry, hematology and urinalysis results.


Estimated Enrollment: 130
Study Start Date: March 2014
Estimated Study Completion Date: April 2020
Estimated Primary Completion Date: April 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ruxolitinib
52 patients- at a starting dose of 10 mg bid. Dose may be adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid.
Drug: ruxolitinib
Supplied as tablets. Starting dose of 10 mg bid. Based on efficacy and safety parameters, dose may be increased or decreased. Maximum dose allowed is 25mg bid.
Active Comparator: Best Available Therapy
52 patients - as selected by the investigator from: Hydroxyurea, IFN/PEG-IFN, popobroman, anagrelide, IMIDs, or observation
Drug: Best Available Therapy
Best Available Therapy as selected by the investigator from the below: 1. Hydroxyurea 2. IFN/PEG-IFN 3. Pipobroman 4. Anagrelide 5. IMIDs 6. Observation only
Other Name: BAT

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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. Other inclusion/exclusion criteria apply.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02038036

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

  Show 74 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02038036     History of Changes
Other Study ID Numbers: CINC424B2401
Study First Received: January 14, 2014
Last Updated: November 3, 2014
Health Authority: Spain: Ministry of Health

Keywords provided by Novartis:
Polycythemia Vera
Hematologic Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Hydroxyurea
INC424
Ruxolitinib

Additional relevant MeSH terms:
Polycythemia
Polycythemia Vera
Bone Marrow Diseases
Hematologic Diseases
Myeloproliferative Disorders
Hydroxyurea
Antineoplastic Agents
Antisickling Agents
Enzyme Inhibitors
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 19, 2014