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Trial record 1 of 1 for:    Oral NS-018 in Patients with Myelofibrosis
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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.
 
ClinicalTrials.gov Identifier: NCT01423851
Recruitment Status : Active, not recruiting
First Posted : August 26, 2011
Last Update Posted : February 26, 2020
Sponsor:
Information provided by (Responsible Party):
NS Pharma, Inc.

Tracking Information
First Submitted Date  ICMJE August 15, 2011
First Posted Date  ICMJE August 26, 2011
Last Update Posted Date February 26, 2020
Study Start Date  ICMJE June 2011
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 24, 2015)
  • 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
  • To establish maximum tolerated dose of NS-018 [ Time Frame: Cycle 1 (28 days) ]
    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 ]
    Phase 2
Original Primary Outcome Measures  ICMJE
 (submitted: August 25, 2011)
  • 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
  • To establish maximum tolerated dose of NS-018 [ Time Frame: Cycle 1 (28 days) ]
    Phase 1
  • To evaluate response to NS-018 treatment using the International Working Group (IWG) consensus criteria, change in spleen size and bone marrow assessment [ Time Frame: Day 29, 57, 85, and every 84 days thereafter ]
    Phase 2
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 24, 2015)
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: August 25, 2011)
  • 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
  • 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
  • To evaluate quality of life assessments using Myelofibrosis Symptom Assessment Form (MF-SAF) [ Time Frame: Day 29, 85, and every 84 days thereafter ]
    Phase 1 and Phase 2
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Tolerability Study of Oral NS-018 in Patients With Primary Myelofibrosis (MF), Post-polycythemia Vera MF or Post-essential Thrombocythemia MF
Official Title  ICMJE 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
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 JAK2 failures into the Phase 2 portion of the study.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Primary Myelofibrosis
  • Post-Polycythemia Vera Myelofibrosis
  • Post-Essential Thrombocythemia Myelofibrosis
Intervention  ICMJE Drug: NS-018
Treatment will be administered continuously as oral daily therapy in cycles of 4 weeks in duration (28 day treatment cycles).
Study Arms  ICMJE Experimental: Intervention: Drug: NS-018
Intervention: Drug: NS-018
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: October 6, 2016)
77
Original Estimated Enrollment  ICMJE
 (submitted: August 25, 2011)
44
Estimated Study Completion Date  ICMJE November 2020
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01423851
Other Study ID Numbers  ICMJE NS-018-101
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party NS Pharma, Inc.
Study Sponsor  ICMJE NS Pharma, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Srdan Verstovsek, M.D., Ph.D. MD Anderson Cancer Center, Houston, TX, 77030
PRS Account NS Pharma, Inc.
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP