INC424 for Patients With Myelofibrosis, Post Polycythemia Myelofibrosis or Post-essential Thrombocythemia Myelofibrosis (MACS1632/2254)
This study is currently recruiting participants.
Verified April 2013 by Novartis
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
First received: December 13, 2011
Last updated: April 17, 2013
Last verified: April 2013
The primary objective of this study is collect additional safety of INC424 in patients with Primary Myelofibrosis, Post Polycythemia Myelofibrosis or Post-essential Thrombocythemia Myelofibrosis, who have either received prior treatment with commercially available agents or who have never received treatment.
Post Polycythemia Myelofibrosis (PPV MF)
Post-essential Thrombocythemia Myelofibrosis (PET-MF)
Post Polycythemia Myelofibrosis
Post-essential Thrombocythemia Myelofibrosis
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
||An Open-label, Multicenter, Expanded Access Study of INC424 for Patients With Primary Myelofibrosis (PMF) or Post Polycythemia Myelofibrosis (PPV MF) or Post-essential Thrombocythemia Myelofibrosis (PET-MF)
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||August 2013 (Final data collection date for primary outcome measure)
|Ages Eligible for Study:
||18 Years to 65 Years
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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 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.
- 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 the adverse drug reactions associated with prior treatment before beginning treatment with INC424
- 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 [Neuopgen; Neulasta], romiplostim, eltrombopag) 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 medication listed in the "Prohibited Medications" listing.
- 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 currently uncontrolled or unstable angina, rapid or paroxysmal atrial fibrillation or recent (approximately 6 months) myocardial infarction or acute coronary syndrome.
- 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.
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG 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.
- 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.
- Women are considered post-memenopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
- Reliable contraception should be maintained throughout the study and for 28 days after study treatment discontinuation
- Patients who are unable to comprehend or are unwilling to sign an informed consent form (ICF)
- Patients with active alcohol or drug addiction that would interfere with their ability to comply with the study requirements
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01493414
|Contact: Novartis Pharmaceuticals
|Contact: Novartis Pharmaceuticals
No publications provided
||Novartis ( Novartis Pharmaceuticals )
History of Changes
|Other Study ID Numbers:
|Study First Received:
||December 13, 2011
||April 17, 2013
||Israel: Ministry of Health
Brazil: Ministry of Health
Canada: Health Canada
Germany: Federal Institute for Drugs and Medical Devices (BfArM)
Italy: Italian Pharmaceutical Agency (AIFA)
Spain: Medicines and Health Products Agency (AEMPS)
Germany: Federal Institute for Drugs and Medical Devices
Keywords provided by Novartis:
post polycythemia myelofibrosis
post-essential thrombocythemia myelofibrosis
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on June 17, 2013
Bone Marrow Diseases
Blood Coagulation Disorders
Blood Platelet Disorders