Clinical trial NCT01558739: Exploratory Phase II Study of INC424 Patients With Primary Myelofibrosis (PMF) or Post Polycythaemia Myelofibrosis (PPV MF) or Post Essential Thrombocythaemia Myelofibrosis (PET-MF)
Official title: A UK Open-label, Multicentre, Exploratory Phase II Study of INC424 for Patients With Primary Myelofibrosis (PMF) or Post Polycythaemia Myelofibrosis (PPV MF) or Post Essential Thrombocythaemia Myelofibrosis (PET-MF)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Primary Myelofibrosis (PMF)
Post Polycythaemia Myelofibrosis (PPV MF)
Post Essential Thrombocythaemia Myelofibrosis (PET-MF)
Keywords: Ruxolitinib
INC424
myelofibrosis
PMF
post polycythemia myelofibrosis
PPV MF
post-essential thrombocythemia myelofibrosis
PET-MF
Primary Myelofibrosis
Polycythemia
Thrombocythemia
Essential Thrombocytosis
myeloproliferative Disorders
Bone Marrow Diseases
Haematologic Diseases
Blood Coagulation Disorders
Blood Platelet Disorders
Haemorrhagic Disorders
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-03-20
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

* 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:

  1. Age \> 65 years;
  2. Presence of constitutional symptoms (weight loss, fever, night sweats); marked anemia (Hgb \< 10g/dL)\*;
  3. Leukocytosis (history of WBC \> 25 x109/L);
  4. 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).

Exclusion criteria:

* 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:

  1. Absolute neutrophil count (ANC) that is ≤ 1000/µL.
  2. 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.

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Percentage of Participants With Treatment Success
timeFrame: 48 Weeks
Secondary outcomes:
measure: Percentage of Participants With Best Overall Response
timeFrame: week 48
measure: Change From Baseline in Myelofibrosis Symptoms Assessment Form (MF-SAF)
timeFrame: Baseline, week 4, week 12, week 24, week 48
measure: Change From Baseline in EQ5D Preference Index (5 Level EuroQol Questionnaire Determining Quality of Life) From Baseline
timeFrame: Baseline, week 4, week 12, week 24, week 48
measure: Number of Hospitalizations
timeFrame: week 12, week 24, week 26, week 48
measure: Duration of Hospitalizations
timeFrame: week 48
measure: Number of Accident & Emergency Visits From Baseline
timeFrame: baseline to week 12, week 12 to week 24, week 24 to week 36, week 36 to week 48
measure: Number of General Practitioner (GP), Specialists' and Urgent Care Visits
timeFrame: baseline to week 12, week 12 to, week 24, week 24 to week 36, week 36 to week 48
measure: Percentage of Participants With Transfusion Dependency Status
timeFrame: baseline (BL), end of treatment (up to 28 days post last treatment) (EOT)
Other outcomes:
Locations:
city: Cardiff
country: United Kingdom
facility: Novartis Investigative Site
state: Wales
city: Bournemouth
country: United Kingdom
facility: Novartis Investigative Site
city: East Yorkshire
country: United Kingdom
facility: Novartis Investigative Site
city: Edinburgh
country: United Kingdom
facility: Novartis Investigative Site
city: Leicester
country: United Kingdom
facility: Novartis Investigative Site
city: Liverpool
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
city: Oxford
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Study Director
role: STUDY_DIRECTOR
References: