Safety Study Evaluating Twice-Daily Administration of Momelotinib in Primary Myelofibrosis or Post-Polycythemia Vera or Post-Essential Thrombocythemia Myelofibrosis
|ClinicalTrials.gov Identifier: NCT01423058|
Recruitment Status : Completed
First Posted : August 25, 2011
Last Update Posted : January 28, 2015
The myeloproliferative neoplasms (MPN), most notably polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) are a diverse but inter-related suite of clonal disorders of pluripotent hematopoietic stem cells (Tefferi et al., 2008). The MPN share a range of biological, pathological, and clinical features including the relative overproduction of one or more cells of myeloid origin, growth factor independent colony formation in vitro, marrow hypercellularity, extramedullary hematopoiesis, spleno- and hepatomegaly, and thrombotic and/or hemorrhagic diatheses (Tefferi et al., 2005).
This is a multi-centre, open-label, non-randomized, dose-escalation study, to be conducted in two phases: a dose-escalation phase (Part 1), to determine the safety and tolerability of momelotinib (CYT387), and to identify a therapeutic dose for the expanded cohort; and a dose-confirmation phase (Part 2), which will be a cohort expansion at or below the MTD of momelotinib.
In the Part I dose-escalation phase of the study, subjects will be assigned to dose levels in successive cohorts starting with a dose in the first cohort of 200 mg BID (twice daily with doses taken approximately 12 hours apart). Doses will be escalated by 50 mg BID per cohort until dose-limiting toxicities are observed. The dose level at which ≥2 of 6 subjects develop a first cycle dose-limiting toxicity (DLT) is defined as the DLT level. The maximum tolerated dose (MTD) is defined as the dose level below the DLT level. New dose levels may begin accrual only if all subjects at the current dose level have been observed for a minimum of 28 days from the first day of treatment. The dose level chosen for study in the dose confirmation phase of the study will be the MTD or a lower dose shown to have significant clinical activity (efficacy) as determined by the safety review committee. Subjects will be evaluated weekly for the first cycle, every 2 weeks during cycle 2, then monthly for 4 cycles for a total of 6 cycles.
In the dose-confirmation phase of the study, approximately fifty (50) subjects will be treated at the MTD or at a lower dose shown to have significant clinical activity (efficacy) as chosen by the Safety Review Committee. In the dose confirmation phase of the study subjects will be evaluated every 2 weeks during the first treatment cycle, and then monthly for 5 cycles for a total of 6 cycles.
|Condition or disease||Intervention/treatment||Phase|
|Primary Myelofibrosis Post-Polycythemia Vera Post-Essential Thrombocythemia Myelofibrosis||Drug: Momelotinib||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||61 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II, Open-Label Study Evaluating Twice-Daily Administration of CYT387 in Primary Myelofibrosis or Post-Polycythemia Vera or Post-Essential Thrombocythemia Myelofibrosis|
|Study Start Date :||August 2011|
|Primary Completion Date :||June 2014|
|Study Completion Date :||June 2014|
In the Part I dose-escalation phase of the study, subjects will be assigned to dose levels in successive cohorts starting with a dose in the first cohort of 200 mg BID (twice daily with doses taken approximately 12 hours apart. Doses will be escalated by 50 mg BID in successive cohorts of 3 subjects per dose level. Subjects will be evaluated weekly for the first cycle, every 2 weeks during cycle 2, then monthly for 4 cycles for a total of 6 cycles.
In the dose confirmation phase of the study (Part 2), subjects will be evaluated every 2 weeks during the first treatment cycle, and then monthly for 5 cycles for a total of 6 cycles.
Other Name: CYT387
- To determine the safety of momelotinib by characterization and relationship of adverse events, affects on vital signs and laboratory parameters, and QTc intervals as measured by electrocardiogram (ECG) [ Time Frame: 6 months ]
- To determine maximum tolerated dose of momelotinib by characterization of Dose Limiting Toxicities [ Time Frame: 6 months ]
- To confirm the half-life of momelotinib by pharmacokinetic analyses [ Time Frame: 6 months ]
- To determine the efficacy of momelotinib by evaluation of spleen and liver size, disease related constitutional symptoms, transfusion dependence and anemia response. [ Time Frame: 6 months ]
- To determine the effect of momelotinib on JAK2V617F mutant allele burden via Polymerase Chain Reaction (PCR) analyses [ Time Frame: 6 months ]
- To determine the effect of momelotinib on plasma levels of inflammatory, fibrogenic and angiogenic cytokines via Enzyme-Linked Immunosorbent Assay (ELISA) [ Time Frame: 6 months ]
- To determine the effect of momelotinib on bone marrow or peripheral blood cytogenetic findings [ Time Frame: 6 months ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01423058
|United States, Arizona|
|Scottsdale, Arizona, United States, 85259|
|United States, Florida|
|Jacksonville, Florida, United States, 32224|
|United States, Texas|
|MD Anderson Cancer Center, The University of Texas|
|Houston, Texas, United States, 77030|
|United States, Utah|
|Huntsman Cancer Institute at the University of Utah|
|Salt Lake City, Utah, United States, 84108|
|Princess Margaret Hospital|
|Toronto, Ontario, Canada, M5G 2M9|
|Jewish General Hospital|
|Montreal, Quebec, Canada, H3T 1E2|
|Study Director:||Mark Kowalski, M.D.||YM Biosciences Inc.|