Location: New Programs :101639
|Program||Chronic Myeloproliferative Neoplasms, Hematology|
|Diagnosis Region||Other Hematopoietic|
|Title||An Open Label Assessment of an Alternative Dosing Strategy of Ruxolitinib in Patients With Primary Myelofibrosis, Post-Polycythemia Vera-Myelofibrosis and Post-Essential Thrombocythemia-Myelofibrosis|
|Sponsor's Number||INCB 18424-261|
|Primary Investigator||Lawrence Afrin email@example.com|
|Study Coordinator||Rachel Whirley 843-792-9579 firstname.lastname@example.org|
Subject Inclusion Criteria
All subjects must meet the following inclusion criteria, based on laboratory and other test findings at the Screening visit unless otherwise indicated:
Subjects who are able to understand and sign an informed consent document.
Subjects 18 years of age or older.
Subjects must be diagnosed with PMF, PPV-MF or PET-MF, according to the investigator’s expert judgment, guided by the criteria outlined in the 2008 World Health Organization criteria (Table 2 in Tefferi and Vardiman, 2008, Appendix I) for PMF, and the proposed criteria for PPV-MF and PET-MF outlined by the International Working Group for Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) (Barosi 2008, Appendix II) irrespective of JAK2 mutation status. A bone marrow biopsy will provide the relevant information. Subjects without circulating blasts at the Screening hematology assessment may use a historical biopsy obtained within the year prior to Screening, provided the report and data are available for the Investigator’s review. Subjects who have detectable circulating peripheral blasts at the Screening assessment may use a historical biopsy only if obtained within 2 months prior to Screening, and all data and reports are available for Investigator’s review. Subjects without a prior biopsy report as indicated above must have a biopsy at Screening or Baseline or will not be able to enroll in the study.
Subjects with MF requiring therapy must have at least 2 points using the DIPSS prognostic criteria developed by the IWG-MRT (Passamonti 2010), using the information from laboratory assessments and ongoing medical history recorded at the Screening Visit.
Subjects in whom treatment of MF is indicated based on the Investigator’s expert judgment.
Subjects with active symptoms of MF at the Screening Visit as demonstrated by presence of one symptom score of at least 5 or two symptom scores of at least 3 using the Screening Symptom Assessment Form (Appendix VII) and/or palpable splenomegaly > 5 cm below the costal margin at the Screening Visit.
Subjects with a palpable spleen.
Subjects with hemoglobin values at the Screening and Baseline visit ≥ 6.5 g/dL and who are willing to receive red blood cell transfusions to treat low hemoglobin levels.
Subjects with a platelet count of at least 100 x109/L at the Screening visit.
Subjects must have discontinued all drugs used to treat underlying MF disease no later than Day -1.
Subjects with an ECOG performance status of 0, 1, 2 or 3 (Appendix VIII).
Subjects with peripheral blood blast count of < 5% at both Screening and Baseline visits.
Subject Exclusion Criteria
Any of the following are causes for exclusion from the study, and must be demonstrated not to be present at the Screening visit (historical laboratory data or other data may not substitute for the Screening findings):
Subjects with a life expectancy of less than 6 months.
Subjects in whom MF disease is well controlled with current therapy.
Females who are pregnant or are currently breastfeeding.
Subjects of childbearing potential who are unwilling to take appropriate precautions (from Screening through Follow-up) to avoid becoming pregnant or fathering a child.
Females of non-childbearing potential are defined as women who (a) are ≥ 55 years of age with history of amenorrhea for 1 year, OR (b) are surgically sterile for at least 3 months.
For females of childbearing potential, or for males, appropriate precautions are those that are at least 99% effective in preventing the occurrence of pregnancy. These methods should be communicated to the subjects and their understanding confirmed. (Appendix III).
Subjects with inadequate bone marrow reserve as demonstrated by:
Absolute neutrophil count (ANC) that is < 1x 109/L at the Screening visit.
Platelet count that is < 100 x 109/L without the assistance of growth factors, thrombopoietic factors or platelet transfusions at either of the Screening and Baseline visits. Subjects must not have received growth factors for at least one month prior to receiving the first dose of ruxolitinib.
Subjects who have received platelet transfusion(s) or who have had ANC levels < 0.5 x109/L in the month prior to Screening.
Subjects with inadequate liver or renal function at Screening and Baseline visits as demonstrated by:
Direct bilirubin ≥ 2.0 x the upper limit of laboratory normal (ULN). (NOTE: direct bilirubin will only be determined if total bilirubin is ≥ 2.0 x ULN).
Alanine aminotransferase (ALT) > 2.5x ULN.
MDRD calculated GFR < 30 mL/min.
Subjects with clinically meaningful, active bacterial, fungal, parasitic or viral infection which require therapy, or who are HIV positive
Subjects with acute infections requiring treatment should delay screening/enrollment until the course of antibiotic therapy has been completed and the event is considered resolved.
Subjects with an invasive malignancy over the previous 5 years except treated early stage carcinomas of the skin, completely resected intraepithelial carcinoma of the cervix and completely resected papillary thyroid and follicular thyroid cancers.
Subjects with recent severe or unstable cardiac disease.
Subjects with end stage renal disease on dialysis.
Subjects who have had splenic irradiation within 6 months prior to receiving the first dose of ruxolitinib.
Subjects being treated concurrently with any prohibited medications (see Section 8.9.2 for specific prohibited medications and the associated timeframe over which they are prohibited).
Subjects who are unable to comprehend or are unwilling to sign an informed consent form (ICF).
Subjects with active alcohol or drug addiction that would interfere with their ability to comply with the study requirements.
Subjects with any concurrent condition that, in the investigator’s opinion, would jeopardize the safety of the subject or compliance with the protocol.
Subjects who have unknown transfusion history for at least the 12 weeks prior to Screening. All transfusions in this time period must be recorded in the electronic case report form (eCRF).
Subjects who are unable to complete the daily symptom diary, which is available in English, Spanish and French versions.
|Hypothesis||-To evaluate the effect of ruxolitinib on spleen volume in subjects with primary myelofibrosis (PMF), post-polycythemia vera-myelofibrosis (PPV-MF) and post-essential thrombocythemia-
-To evaluate the effect of ruxolitinib on symptomatic burden, palpable spleen length, Patient’s Global Impression of Change, quality of life and PD/PK parameters
-To evaluate the safety and tolerability of ruxolitinib
|Available Documents|| HIPAA |