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)
- 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
- 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
- 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).
- 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
- 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
- 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.