An open-label, multicenter, expanded access study of INC424 (ruxolitinib) for patients with primary myelofibrosis (PMF) or post-polycythemia Myelofibrosis (PPV MF) or post-essential thrombocythemia myelofibrosis (PET-MF).

Study Objectives

Primary Objective

To collect additional safety information on INC424 (ruxolitinib) when used in patients with PMF, PPV MF, or PET-MF who have either received prior treatment with commercially available agents or who have never received treatment.

Secondary Objective(s)

• To assess the best overall response rate of INC424 (ruxolitinib) in patients with PMF, PPV MF, or PET-MF.
• To collect quality of life information from patients with PMF, PPV MF, or PET-MF and treated with INC424 (ruxolitinib).
• To document medical resource utilization (MRU) from patients with PMF, PPV MF, or PETMF and treated with INC424 (ruxolitinib).

Participation conditions

Inclusion Criteria

• Patients must give written informed consent according to local guidelines prior to any screening procedures.
• Patients must not be eligible for another ongoing INC424 clinical trial.
• Male or female patients aged ≥ 18 years of age.
• Patients must be diagnosed with PMF, PPV-MF or PET-MF, according to the 2008 World Health Organization criteria (Appendix I), irrespective of JAK2 mutation status.
• PMF patients 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 (Cervantes 2009) are described in Section 1.1.
• Patients with Intermediate-1 and splenomegaly, must have a palpable spleen measuring 5 cm or greater from the costal margin to the point of greatest splenic protrusion.
• Patients with 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 Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (Appendix V).
• Women of childbearing potential must have had a negative serum pregnancy test within 14 days prior to the administration of study drug.
• Patients must have recovered or stabilized sufficiently from adverse drug reactions associated with prior treatments before beginning treatment with INC424

Exclusion Criteria

•  Patients eligible for hematopoietic stem cell transplantation (suitable candidate and a suitable donor is available).
• Patients with a history of malignancy in the 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, granulocyte colony stimulating factor at any time within 2 weeks prior to Screening or 4 weeks prior to baseline.
• Patients currently participating in COMFORT-I and COMFORT-II trials.
• Patients receiving any medications listed in the “prohibited medications”.
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of INC424.
• 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 currently uncontrolled or unstable angina, rapid or paroxysmal fibrillation or recent myocardial infarction or acute coronary syndrome.
• Patients with clinically significant bacterial, fungal, parasitic or viral infection that requires 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:
  • a. Absolute neutrophil count (ANC) that is ≤ 1000/μL.
  • b. 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)≥.5 x ULN.
• Patients with known hypersensitivity to INC424 or other JAK1/JAK2 inhibitors, or to its excipients.
• Patients receiving ongoing treatment with another investigational medication or having been treated with an investigational medication within 30 days of study drug treatment.
• Pregnant or nursing women, where pregnancy is defined as the state of a female after conception and until termination of gestation, confirmed by a positive βHCG laboratory test (> 5 mIU/mL).
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means,
• UNLESS they are using two birth control methods. The two methods can be a double barrier method or a barrier method plus a hormonal method (see Appendix III).
  • a. Adequate barrier methods of contraception include: diaphragm, condom (by the partner), intrauterine device (copper or hormonal), sponge or spermicide. Hormonal contraceptives include any marketed contraceptive agent that includes an estrogen and/or a progestational agent.
  • b. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous)
     

CHL