NCT01558739

Brief Summary

The primary objective of this study is to evaluate the efficacy of INC424 in patients with PMF, PPV MF, or PET-MF using a composite measure of either an objective endpoint (\> 50% reduction in splenomegaly using palpitation at 48 weeks) and/or a subjective endpoint (\>50% reduction in total symptom score at 48 weeks).

Trial Health

87
On Track

Trial Health Score

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

Enrollment
48

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started May 2012

Geographic Reach
1 country

10 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

March 16, 2012

Completed
4 days until next milestone

First Posted

Study publicly available on registry

March 20, 2012

Completed
1 month until next milestone

Study Start

First participant enrolled

May 1, 2012

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2014

Completed
1.2 years until next milestone

Results Posted

Study results publicly available

March 3, 2015

Completed
Last Updated

March 3, 2015

Status Verified

March 1, 2015

Enrollment Period

1.7 years

First QC Date

March 16, 2012

Results QC Date

January 26, 2015

Last Update Submit

March 1, 2015

Conditions

Primary Myelofibrosis (PMF)Post Polycythaemia Myelofibrosis (PPV MF)Post Essential Thrombocythaemia Myelofibrosis (PET-MF)

Keywords

RuxolitinibINC424myelofibrosisPMFpost polycythemia myelofibrosisPPV MFpost-essential thrombocythemia myelofibrosisPET-MFPrimary MyelofibrosisPolycythemiaThrombocythemiaEssential Thrombocytosismyeloproliferative DisordersBone Marrow DiseasesHaematologic DiseasesBlood Coagulation DisordersBlood Platelet DisordersHaemorrhagic Disorders

Outcome Measures

Primary Outcomes (1)

  • Percentage of Participants With Treatment Success

    Treatment success was defined as a 50% or greater reduction in palpable spleen length versus baseline at 48 weeks and/or a 50% or greater improvement in total symptom score (derived from the MF symptom assessment form (MFSAF) questionnaire) versus baseline at the week 48 time point. The MFSAF assesses the following symptoms (all scored from absent (0) to worst imaginable (10)): general fatigue, abdominal pain (and discomfort), inactivity (ability to move and walk around), cough, night sweats, itching (pruritus), bone pain (diffuse not joint pain or arthritis), fever, change in appetite/unintentional weight loss (or gain) in past 6 months, overall quality of life (QoL).

    48 Weeks

Secondary Outcomes (8)

  • Percentage of Participants With Best Overall Response

    week 48

  • Change From Baseline in Myelofibrosis Symptoms Assessment Form (MF-SAF)

    Baseline, week 4, week 12, week 24, week 48

  • Change From Baseline in EQ5D Preference Index (5 Level EuroQol Questionnaire Determining Quality of Life) From Baseline

    Baseline, week 4, week 12, week 24, week 48

  • Number of Hospitalizations

    week 12, week 24, week 26, week 48

  • Duration of Hospitalizations

    week 48

  • +3 more secondary outcomes

Study Arms (1)

INC424

EXPERIMENTAL

Patients diagnosed with PMF, PPV MF, or PET-MF were treated with oral INC424 at a dose of 15 - 20 mg (dose based on Baseline platelet count) twice daily.

Drug: INC424

Interventions

INC424DRUG

Ruxolitinib was provided in 5 mg tablets, packaged in bottles. 15 - 20 mg (dose based on Baseline platelet count) twice daily.

INC424

Eligibility Criteria

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

You may qualify if:

  • Patients must not be eligible for another ongoing INC424 clinical trial.
  • Patients must be diagnosed with PMF, PPV MF or PET-MF, according to the 2008 revised World Health Organization criteria irrespective of JAK2 mutation status.
  • Patients with PMF requiring therapy must be classified as high risk (3 prognostic factors) OR intermediate risk level 2 (2 prognostic factors, no more), OR intermediate risk level 1 (1 prognostic factor, no more) with an enlarged spleen. The prognostic factors, defined by the International Working Group are:
  • Age \> 65 years;
  • Presence of constitutional symptoms (weight loss, fever, night sweats); marked anemia (Hgb \< 10g/dL)\*;
  • Leukocytosis (history of WBC \> 25 x109/L);
  • Circulating blasts \> 1%. • A hemoglobin value \< 10 g/dL must be demonstrated during the Screening Visit for patients who are not transfusion dependent. Patients receiving regular transfusions of packed red blood cells will be considered to have hemoglobin \< 10 g/dL for the purpose of evaluation of risk factors.
  • Patients with Intermediate-1 disease and splenomegaly must have a palpable spleen measuring 5 cm or greater from the costal margin to the point of greatest splenic protrusion.
  • Patients must have a peripheral blood blast count of \< 10%.
  • Patients with adequate liver function defined as direct bilirubin ≤ 2.0 x ULN and ALT ≤ 2.5 x ULN.
  • Patients with adequate renal function defined as serum creatinine ≤ 2 x ULN.
  • Patients with an ECOG performance status of 0, 1, or 2 (Appendix 5).

You may not qualify if:

  • Patients eligible for hematopoietic stem cell transplantation (suitable candidate and a suitable donor is available).
  • Patients with history of malignancy in past 3 years except for treated, early-stage squamous or basal cell carcinoma in situ.
  • Patients undergoing treatment with hematopoietic growth factor receptor agonists (i.e., erythropoietin \[Epo\], granulocyte colony stimulating factor (GCSF \[Neupogen; Neulasta\], romiplostim, eltrombopag) at any time within 2 weeks prior to Screening or 4 weeks prior to Baseline.
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral INC424 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection).
  • Patients with cardiac disease which in the Investigator's opinion may jeopardize the safety of the patient or the compliance with the protocol.
  • Patients with clinically significant bacterial, fungal, parasitic or viral infection which require therapy. Patients with acute bacterial infections requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed.
  • Patients with known active hepatitis A, B, C or who are HIV-positive.
  • Patients with inadequate bone marrow reserve as demonstrated by:
  • Absolute neutrophil count (ANC) that is ≤ 1000/µL.
  • Platelet count that is \< 100,000/µL without the assistance of growth factors, thrombopoietic factors or platelet transfusions.
  • Patients with any history of platelet counts \< 50,000/µL or ANC \< 500/µL except during treatment for a myeloproliferative disorder or treatment with cytotoxic therapy for any other reason.
  • Patients with coagulation parameters (PT, PTT, INR) ≥ 1.5.
  • Patients with known hypersensitivity to INC424 or other JAK1/2 inhibitors, or to their excipients.
  • Patients under ongoing treatment with another investigational medication or having been treated with an investigational medication within 30 days of screening.
  • Patients with any concurrent condition that, in the Investigator's opinion would jeopardize the safety of the patient or compliance with the protocol.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

Novartis Investigative Site

Cardiff, Wales, CF14 4XN, United Kingdom

Location

Novartis Investigative Site

Bournemouth, BH7 7DW, United Kingdom

Location

Novartis Investigative Site

East Yorkshire, HU16 5JQ, United Kingdom

Location

Novartis Investigative Site

Edinburgh, EH4 2XU, United Kingdom

Location

Novartis Investigative Site

Leicester, LE7 5WW, United Kingdom

Location

Novartis Investigative Site

Liverpool, L7 8XP, United Kingdom

Location

Novartis Investigative Site

London, SE1 9RT, United Kingdom

Location

Novartis Investigative Site

London, W12 0HS, United Kingdom

Location

Novartis Investigative Site

Manchester, M13 9NT, United Kingdom

Location

Novartis Investigative Site

Oxford, OX3 7LJ, United Kingdom

Location

MeSH Terms

Conditions

Primary MyelofibrosisPolycythemiaThrombocytosisThrombocythemia, EssentialMyeloproliferative DisordersBone Marrow DiseasesBlood Coagulation DisordersBlood Platelet DisordersHemorrhagic Disorders

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Hematologic DiseasesHemic and Lymphatic Diseases

Results Point of Contact

Title
Study Director
Organization
Novartis Pharmaceuticals
862-778-8300

Study Officials

  • Study Director

    Novartis Pharmaceuticals

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 4
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 16, 2012

First Posted

March 20, 2012

Study Start

May 1, 2012

Primary Completion

January 1, 2014

Study Completion

January 1, 2014

Last Updated

March 3, 2015

Results First Posted

March 3, 2015

Record last verified: 2015-03

Locations

GB(10)