Safety and Tolerability Study of Oral NS-018 in Patients With Primary Myelofibrosis (MF), Post-polycythemia Vera MF or Post-essential Thrombocythemia MF

NCT ID: NCT01423851

Last Updated: 2022-03-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 77 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-06-30
• Study Completion Date: 2020-04-22

Brief 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)

Detailed Description

This is a Phase 1/2 study that is currently enrolling Janus kinase 2 (JAK2) failures into the Phase 2 portion of the study.

Conditions

Primary Myelofibrosis; Post-Polycythemia Vera Myelofibrosis; Post-Essential Thrombocythemia Myelofibrosis

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intervention: Drug: NS-018

In Phase 1 part, subjects were treated with oral NS-018 at a dose of 75 - 400 mg once daily or 100 - 400 mg twice daily. In Phase 2 part, subjects were treated with oral NS-018 at a dose of 300 mg once daily.

Group Type: EXPERIMENTAL

NS-018

Intervention Type: DRUG

Treatment will be administered continuously as oral daily therapy in cycles of 4 weeks in duration (28 day treatment cycles).

Interventions

NS-018

Treatment will be administered continuously as oral daily therapy in cycles of 4 weeks in duration (28 day treatment cycles).

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NS Pharma, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Srdan Verstovsek, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

MD Anderson Cancer Center, Houston, TX, 77030

Locations

Mayo Clinic Scottsdale Recruiting

Scottsdale, Arizona, United States

UC San Diego Moores Cancer Center

San Diego, California, United States

Mayo Clinic, Jacksonville

Jacksonville, Florida, United States

Northwestern University

Chicago, Illinois, United States

University of Chicago

Chicago, Illinois, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Weill Cornell Medical College

New York, New York, United States

MD Anderson Cancer Center, Department of Leukemia

Houston, Texas, United States

Countries

United States

References

Verstovsek S, Talpaz M, Ritchie E, Wadleigh M, Odenike O, Jamieson C, Stein B, Uno T, Mesa RA. A phase I, open-label, dose-escalation, multicenter study of the JAK2 inhibitor NS-018 in patients with myelofibrosis. Leukemia. 2017 Feb;31(2):393-402. doi: 10.1038/leu.2016.215. Epub 2016 Aug 1.

Reference Type: DERIVED

PMID: 27479177 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NS-018-101

Identifier Type: -

Identifier Source: org_study_id