A Phase 1/2 interventional study of CYT387 in Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis and Post-Essential Thrombocythemia Myelofibrosis, sponsored by Sierra Oncology LLC - a GSK company. Completed at 6 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-02-01.
Sponsored by Sierra Oncology LLC - a GSK company · Phase 1/2, Interventional, and Treatment
This study seeks to (i) determine a safe and tolerated dose of CYT387 (momelotinib) given to patients with PMF, post-PV or post-ET and, (ii) assess the effectiveness of orally-administered CYT387 as a treatment for PMF, post-PV or post-ET.
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, splenomegaly and hepatomegaly, and thrombotic and/or hemorrhagic diatheses (Tefferi et al., 2005).
This is an open-label, non-randomized, dose-escalation study, to be conducted in two phases: a single-centre dose-escalation phase with supernumerary patient addition (Part 1), to determine the safety and tolerability of CYT387, and to identify a therapeutic dose for the confirmation portion of the study; and a multiple-centre dose-confirmation phase (Part 2), which will be a cohort expansion at or below the maximum tolerated dose (MTD) of CYT387.
In Part 1 of the study, patients will be assigned to dose levels in successive cohorts starting with a dose in the first cohort of 100 mg/day, administered orally as a single daily dose (ie QD: at least 20 and no more than 28 hours apart, preferably in a fasted state at least one hour before and two hours after a meal). Dose-escalation will proceed initially with a 1.5-fold increment however, based on toxicity and efficacy information at a specific dose level, the dose escalation increment may be reduced to a 1.25-fold escalation at the discretion of the investigator. At any dose level, if one patient experiences a Grade 2 toxicity or higher, the dose-escalation may only proceed with 1.25-fold increments.
The MTD is defined as the highest dose level at which > 2 of 6 subjects develop first cycle DLT. 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 recommended Phase II dose will be the MTD unless significant clinical activity (efficacy) is seen below the MTD. With the exception of the first cohort, dose levels may be decreased from the intended dose levels for the next cohort, if Grade 2 or greater toxicities are observed.
Twenty (20) patients will be assigned to receive CYT387 at 150 mg twice daily (BID) with doses approximately 10-12 hours apart to determine the comparative safety, tolerability and preliminary activity of CYT387 administered twice-daily. Initially, a maximum of 6 (six) patients will be enrolled for safety assessment. If none of the six patients experiences a first-cycle DLT, then the remaining 14 patients may be enrolled following approval by the Data Safety Monitoring Board (DSMB).
In the multi-centre portion of the study (Part 2), sixty (60) additional patients will be dosed at either 150 mg or 300 mg once daily (QD). Subjects will be evaluated weekly for the first cycle, every 2 weeks for cycle 2, and at the end of each subsequent cycle for up to 9 cycles of CYT387 treatment. If, after 6 months of therapy an individual patient has not experienced a drug-related serious adverse event (SAE), the investigator may, with the written concurrence of the independent safety monitor, elect to have that patient's monthly safety assessment performed by a registered medical practitioner remote to the investigational centre. Subjects will return for a follow-up visit 30 days after completion of the last dose of study drug. Subjects who achieve at least stable disease or better and tolerate the drug well may be allowed to continue to receive CYT387 beyond the planned 9 cycles under the extension protocol CCL09101E.
228 studies on the registry are indexed under Polycythemia Vera; 53 are open to participants now.
This study's enrollment of 166 is above the median of 55 across 174 interventional studies indexed under Polycythemia Vera.
Browse Polycythemia Vera studies →Sierra Oncology LLC - a GSK company is the lead sponsor of 19 studies on the registry; none are open to participants now.
Of its 8 completed or terminated interventional studies of FDA-regulated products, 5 (63%) have results posted.
Counted across the registry records on this site, refreshed daily.
Must have evidence of acceptable organ function within 7 days of initiating study drug as evidenced by the following:
Exclusion Criteria:
Drug: CYT387
For the Part 1 dose-escalation portion of the study, patients will be assigned to dose levels in successive cohorts starting with a dose in the first cohort of 100 mg/day. CYT387 will be orally self-administered as a single daily dose beginning on Day 1 of the study, and thereafter at approximately the same time each day of the 28-day cycle. It is recommended that all doses be preceded by a 2-hour fast from food and beverages, and be followed by a 1-hour post-dose fast from food and beverages. Twenty additional patients will be assigned to a 150 mg BID (twice daily) dosing schedule. CYT387 will be orally self-administered twice-daily with doses approximately 10-12 hours apart beginning on Day 1 of the study, and thereafter at approximately the same times each day of the 28-day cycle. For the Part 2 dose confirmation portion of the study, patients will be assigned to either 150 mg or 300 mg QD (once daily) dose groups.
Also known as: Momelotinib
Safety and tolerability, dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of orally-administered CYT387 in patients with PMF or post-ET/PV MF.
Time frame: Ongoing throughout therapy up until 30 days after last dose of CYT387
Objective Response Rate (ORR), as measured by complete response (CR) rate, partial response (PR) rate and clinical improvement (CI) rate according to International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) consensus criteria
The Objective Response Rate (ORR), as measured by complete response (CR) rate, partial response (PR) rate and clinical improvement (CI) rate according to International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) is to be measured at the end of every cycle of therapy.
Time frame: Baseline to study completion
Pharmacokinetics of CYT387 in patients with PMF or post-ET/PV MF
The pharmacokinetics (PK) of CYT387 in patients with PMF or post-ET/PV MF is to be assessed on Day 1 and Day 28 in Cycle 1 of therapy
Time frame: Baseline to end of Cycle 1
Effect of CYT387 on bone marrow or peripheral blood cytogenetic findings in patients with PMF or post-ET/PV MF.
The effect of CYT387 on bone marrow or peripheral blood cytogenetic findings in patients with PMF or post-ET/PV MF is to be assessed at the end of every third cycle of therapy.
Time frame: Baseline to study completion
Effect of CYT387 on peripheral blood granulocyte JAK2V617F allele burden in patients with PMF or post-ET/PV MF.
The effect of CYT387 on peripheral blood granulocyte JAK2V617F allele burden in patients with PMF or post-ET/PV MF is to be assessed at the end of each cycle of therapy (in relevant patients only)
Time frame: Baseline to study completion
Effect of CYT387 on peripheral blood endogenous myeloid colony formation in patients with PMF or post-ET/PV MF.
The effect of CYT387 on peripheral blood endogenous myeloid colony formation in patients with PMF or post-ET/PV MF is to be assessed at the end of each cycle of therapy.
Time frame: Baseline to study completion
Effect of CYT387 on plasma levels of inflammatory, fibrogenic and angiogenic cytokines in patients with PMF or post-ET/PV MF
The effect of CYT387 on plasma levels of inflammatory, fibrogenic and angiogenic cytokines in patients with PMF or post-ET/PV MF is to be assessed at the end of each cycle of therapy.
Time frame: Baseline to study completion
Pharmacodynamic correlates of CYT387 activity in patients with PMF or post-ET/PV MF who are receiving treatment with CYT387.
The pharmacodynamic correlates of CYT387 activity in patients with PMF or post-ET/PV MF who are receiving treatment with CYT387 are to be assessed on Day 1 of Cycles 1, 3, 6 and 9.
Time frame: Baseline to Cycle 9
This study is completed, as verified in Jan 2019. You cannot join it, but the record below documents what was studied.
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Sierra Oncology LLC - a GSK company