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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01423851
Recruitment Status : Active, not recruiting
First Posted : August 26, 2011
Last Update Posted : February 26, 2020
Information provided by (Responsible Party):
NS Pharma, Inc.

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)

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

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 77 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : June 2011
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2020

Arm Intervention/treatment
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).

Primary Outcome Measures :
  1. 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) ]
    Phase 1 and Phase 2

  2. To establish maximum tolerated dose of NS-018 [ Time Frame: Cycle 1 (28 days) ]
    Phase 1

  3. 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 ]
    Phase 2

Secondary Outcome Measures :
  1. 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 ]
    Phase 1 and Phase 2

  2. To evaluate pharmacodynamic correlates of NS-018 [ Time Frame: Day 1, 8, 15, 29, 57, 85, and every 84 days thereafter ]
    Phase 1 and Phase 2

  3. 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 ]
    Phase 1 and Phase 2

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01423851

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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.
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Principal Investigator: Srdan Verstovsek, M.D., Ph.D. MD Anderson Cancer Center, Houston, TX, 77030
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: NS Pharma, Inc. Identifier: NCT01423851    
Other Study ID Numbers: NS-018-101
First Posted: August 26, 2011    Key Record Dates
Last Update Posted: February 26, 2020
Last Verified: February 2020
Keywords provided by NS Pharma, Inc.:
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:
Bone Marrow Diseases
Hematologic Diseases
Polycythemia Vera
Thrombocythemia, Essential
post-PV MF
post-ET MF
Additional relevant MeSH terms:
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Polycythemia Vera
Primary Myelofibrosis
Thrombocythemia, Essential
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Bone Marrow Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders