Overview

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

Summary

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 No locations recruiting
Other countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
ns-018
Treatment will be administered continuously as oral daily therapy in cycles of 4 weeks in duration (28 day treatment cycles).

Primary Outcomes

Measure
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

Measure
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..
Location data was received from the National Cancer Institute and was last updated in October 2016.