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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2015 by NS Pharma, Inc.
Information provided by (Responsible Party):
NS Pharma, Inc. Identifier:
First received: August 15, 2011
Last updated: September 24, 2015
Last verified: September 2015
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)

Condition Intervention Phase
Primary Myelofibrosis
Post-Polycythemia Vera Myelofibrosis
Post-Essential Thrombocythemia Myelofibrosis
Drug: NS-018
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by NS Pharma, Inc.:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: Yes ]
    Phase 1 and Phase 2

  • To establish maximum tolerated dose of NS-018 [ Time Frame: Cycle 1 (28 days) ] [ Designated as safety issue: Yes ]
    Phase 1

  • 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 ] [ Designated as safety issue: No ]
    Phase 2

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Phase 1 and Phase 2

  • To evaluate pharmacodynamic correlates of NS-018 [ Time Frame: Day 1, 8, 15, 29, 57, 85, and every 84 days thereafter ] [ Designated as safety issue: No ]
    Phase 1 and Phase 2

  • 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 ] [ Designated as safety issue: No ]
    Phase 1 and Phase 2

Estimated Enrollment: 68
Study Start Date: June 2011
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intervention: Drug: NS-018 Drug: NS-018
Treatment will be administered continuously as oral daily therapy in cycles of 4 weeks in duration (28 day treatment cycles).

Detailed Description:
This is a Phase 1/2 study that is currently enrolling JAK2 failures into the Phase 2 portion of the study.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01423851

United States, Arizona
Mayo Clinic Scottsdale Recruiting Recruiting
Scottsdale, Arizona, United States, 85259-5499
Contact: Clinical Trials Office - All Mayo Clinic Locations    507-538-7623      
Principal Investigator: Ruben A. Mesa, M.D.         
United States, California
UC San Diego Moores Cancer Center Recruiting
San Diego, California, United States, 92093-0698
Contact: Reilly Kidwell    858-534-4801   
Principal Investigator: Catriona Jamieson, MD, PhD         
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Stephanie Terns    312-695-1354   
Principal Investigator: Brady Stein, MD         
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Lisa Pape    773-702-6206   
Contact: Peggy Green    773-7702-0267   
Principal Investigator: Olatoyosi Odenike, MD         
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Sarah Patches   
Principal Investigator: Martha Wadleigh, MD         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Nabeela Iqbal   
Principal Investigator: Moshe Talpaz, MD         
United States, New York
Weill Cornell Medical College Recruiting
New York, New York, United States, 10021
Contact: Ruth Bauman   
Principal Investigator: Ellen Ritchie, MD         
United States, Texas
MD Anderson Cancer Center, Department of Leukemia Recruiting
Houston, Texas, United States, 77030
Contact: Srdan Verstovsek, M.D., Ph.D.    713-745-3429   
Principal Investigator: Srdan Verstovsek, M.D., Ph.D.         
Sponsors and Collaborators
NS Pharma, Inc.
Principal Investigator: Srdan Verstovsek, M.D., Ph.D. MD Anderson Cancer Center, Houston, TX, 77030
  More Information

Responsible Party: NS Pharma, Inc. Identifier: NCT01423851     History of Changes
Other Study ID Numbers: NS-018-101 
Study First Received: August 15, 2011
Last Updated: September 24, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by NS Pharma, Inc.:
Bone Marrow Diseases
Hematologic Diseases
Keywords provided by NS Pharma, Inc.:
JAK2 kinase inhibitor
Myeloproliferative Neoplasms
Primary Myelofibrosis
post-Polycythemia Vera Myelofibrosis
post-Essential Thrombocythemia Myelofibrosis
Additional relevant MeSH terms:
Polycythemia Vera
Thrombocythemia, Essential
post-PV MF
post-ET MF

Additional relevant MeSH terms:
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders
Primary Myelofibrosis
Polycythemia Vera
Thrombocythemia, Essential processed this record on September 27, 2016