This trial is active, not recruiting.

Conditions primary myelofibrosis, post-polycythemia vera myelofibrosis, post-essential thrombocythemia myelofibrosis
Treatment ns-018
Phase phase 1/phase 2
Sponsor NS Pharma, Inc.
Start date June 2011
End date October 2016
Trial size 77 participants
Trial identifier NCT01423851, NS-018-101


The purpose of this study is to determine the safety and tolerability of orally administered NS-018 in patients with Primary Myelofibrosis (PMF), Post-polycythemia Vera Myelofibrosis (post-PV MF), or Post-essential Thrombocythemia Myelofibrosis (post-ET MF)

United States Arizona, California, Illinois, Michigan, Minnesota, and Texas
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Treatment will be administered continuously as oral daily therapy in cycles of 4 weeks in duration (28 day treatment cycles).

Primary Outcomes

To evaluate safety and tolerability of NS-018 assessed by the type, frequency, seriousness and intensity of adverse events
time frame: Throughout the study until 30 days after the last dose of study drug (patients with disease progression or no clinical benefit after 6 cycles [168 days] will be discontinued from the study)
To establish maximum tolerated dose of NS-018
time frame: Cycle 1 (28 days)
To evaluate response to NS-018 treatment using the International Working Group-Myeloproliferative Neoplasms Research and treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus, change in spleen size and bone marrow assessment
time frame: Day 29, 57, 85, and every 84 days thereafter

Secondary Outcomes

To determine the pharmacokinetic parameters of NS-018 (Cmax, Tmax, AUC, t1/2 and accumulation ratio)
time frame: Up to 24 hours post-dose on Day 1, 8, 15, 29
To evaluate pharmacodynamic correlates of NS-018
time frame: Day 1, 8, 15, 29, 57, 85, and every 84 days thereafter
To evaluate quality of life assessments using Myelofibrosis Symptom Assessment Form (MF-SAF) for Phase 1 and the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) for Phase 2.
time frame: Day 29, 85, and every 84 days thereafter

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Primary myelofibrosis, post-PV MF, or post-ET MF that requires therapy - MF patients must have received prior JAK2 inhibitor therapy, and been found to be intolerant, or refractory/relapsed from prior JAK2 inhibitor therapy, based on investigator assessment - ≥18 years old - ECOG Performance Status of ≤ 3 - Estimated life expectancy of ≥12 weeks - Male or non-pregnant, non-lactating female patients - Serum creatinine of ≤1.5 × the upper limit of normal (ULN)OR estimated creatinine clearance (CrCl) ≥ 40 ml/min/1.73 m2 - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × the upper limit of normal (ULN) and total bilirubin ≤1.5 × ULN. If the total bilirubin is elevated between 1.5 x and 3 x ULN, patients with a direct bilirubin ≤ 1.5 X ULN are eligible during the Phase II portion. - Absolute neutrophil count (ANC) >1000/μL and Platelet count > 25,000/μL - QTcB ≤ 480 msec - No MF-directed treatment for at least 2 weeks prior to initiation of NS-018, including any use of corticosteroids for Myelofibrosis symptom or blood count management. Low dose corticosteroids ≤ 10 mg/day prednisone or equivalent is allowed for non-myelofibrosis purposes. Exclusion Criteria: - Active, uncontrolled systemic infection - Patients with any unresolved toxicity greater than Grade 1 from previous anticancer therapy - Potentially curative therapy is available - Currently taking medication that is substantially metabolized by cytochrome P450 (CYP) 1A2 or CYP3A4 or taking medication known to be strong inhibitors or inducers of CYP3A4 - Patients with a serious cardiac condition within the past 6 months - Pregnant or lactating - Radiation therapy for splenomegaly within 6 months prior to study entry - Splenectomy (Phase 2 portion of the study only) - Known HIV positive status - Known active hepatitis, a history of viral hepatitis B or hepatitis C

Additional Information

Official title A Phase 1/2, Open-label, Dose-Escalation Multi-center Study to Assess the Safety, Tolerability, PK and PD of Orally Administered NS-018 in Patients With Primary Myelofibrosis (MF), Post-polycythemia Vera MF, or Post-essential Thrombocythemia MF
Principal investigator Srdan Verstovsek, M.D., Ph.D.
Description This is a Phase 1/2 study that is currently enrolling JAK2 failures into the Phase 2 portion of the study.
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by NS Pharma, Inc..