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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 ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
NS Pharma, Inc.
ClinicalTrials.gov Identifier:
NCT01423851
First received: August 15, 2011
Last updated: October 6, 2016
Last verified: October 2016
  Purpose
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


Enrollment: 77
Study Start Date: June 2011
Estimated Study Completion Date: October 2019
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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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 ClinicalTrials.gov identifier: NCT01423851

Locations
United States, Arizona
Mayo Clinic Scottsdale Recruiting
Scottsdale, Arizona, United States, 85259-5499
United States, California
UC San Diego Moores Cancer Center
San Diego, California, United States, 92093-0698
United States, Florida
Mayo Clinic, Jacksonville
Jacksonville, Florida, United States, 32224
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
University of Chicago
Chicago, Illinois, United States, 60637
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, New York
Weill Cornell Medical College
New York, New York, United States, 10021
United States, Texas
MD Anderson Cancer Center, Department of Leukemia
Houston, Texas, United States, 77030
Sponsors and Collaborators
NS Pharma, Inc.
Investigators
Principal Investigator: Srdan Verstovsek, M.D., Ph.D. MD Anderson Cancer Center, Houston, TX, 77030
  More Information

Responsible Party: NS Pharma, Inc.
ClinicalTrials.gov Identifier: NCT01423851     History of Changes
Other Study ID Numbers: NS-018-101 
Study First Received: August 15, 2011
Last Updated: October 6, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by NS Pharma, Inc.:
Keywords provided by NS Pharma, Inc.:
JAK2 kinase inhibitor
NS-018
Myeloproliferative Neoplasms
Primary Myelofibrosis
post-Polycythemia Vera Myelofibrosis
post-Essential Thrombocythemia Myelofibrosis
Additional relevant MeSH terms:
Bone Marrow Diseases
Hematologic Diseases
Polycythemia Vera
Thrombocythemia, Essential
PMF
post-PV MF
post-ET MF

Additional relevant MeSH terms:
Primary Myelofibrosis
Polycythemia
Polycythemia Vera
Thrombocytosis
Thrombocythemia, Essential
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders

ClinicalTrials.gov processed this record on December 07, 2016