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

NCT01423851 | Completed Phase 1 Results DMC

• 1 other identifier: NS-018-101
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 9

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)

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (4)

• Part 1 and Part 2: Number of Subjects With Adverse Events and Serious Adverse Event

  AEs (non-serious, serious) as variables of safety and tolerability of NS-018 were assesed. The number of patients were presented as Overall summary of AEs including treatment-emergent AEs (TEAEs); Treatment-emergent SAEs; Drug-related TEAEs; Treatment-emergent AEs leading to permanent discontinuation of study drug; Hospitalization or prolongation of existing hospitalization; Death.

  From screening to until study discontinuation (approximate 8 years 10 months)

• Part 2: Number of Patient With Objective Response Using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European Leukemia Net (ELN)

  Six response categories are listed: complete remission (CR) and partial remission signify treatment effects that are consistent with disease modification, whereas drug-induced improvements in MF-symptomatic burden were annotated as clinical improvement, anemia response, spleen response, orsymptoms response. Additional criteria are provided for progressive disease, stable disease, and relapse. The objective response was defined as the number of patients with confirmed complete remission (CR) + partial response (PR) + clinical improvement (CI) during the treatment period.

  Cycle 7 Day 1 (duration of cycle was 4 weeks)

• Part 2: Change From Baseline in Spleen Size

  Change from baseline in spleen size was assessed by magnetic resonance imaging (MRI) (computed tomography \[CT\] scan for patients not able to tolerate MRI).

  From Baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)

• Part 2: Change From Baseline in Bone Marrow Assessment

  Bone marrow was assessed by aspiration and biopsy for grade changes in osteomyelofibrosis. Fibrosis was graded according to European Consensus Myelofibrosis Grading Criteria, ranging from grade 0, which corresponds to normal bone marrow, to grade 3, in which coarse bundles of collagen fibrosis are identifiable with significant osteosclerosis.

  From baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)

Secondary Outcomes (12)

• Part 1: Number of Patients With Objective Response Using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)

  Cycle 7 Day 1 (duration of cycle was 4 weeks)

• Part 1: Change From Baseline in Spleen Size

  From Baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)

• Part 1: Change From Baseline in Bone Marrow Assessment

  From baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)

• Part 1: Change From Baseline in Quality of Life Assessments Using Myelofibrosis Symptom Assessment Form (MF-SAF)

  From baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)

• Part 2: Change From Baseline in Quality of Life Assessments Using Myeloproliferative Neoplasm Symptom Assessment Form (MPN SAF (MPN 10)

  From baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)

Study Arms (1)

Intervention: Drug: NS-018

EXPERIMENTAL

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.

Drug: NS-018

Interventions

NS-018 DRUG

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

Intervention: Drug: NS-018

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• NS Pharma, Inc.: lead

Study Sites (9)

Mayo Clinic Scottsdale Recruiting

Scottsdale, Arizona, 85259-5499, United States

Location

UC San Diego Moores Cancer Center

San Diego, California, 92093-0698, United States

Location

Mayo Clinic, Jacksonville

Jacksonville, Florida, 32224, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Weill Cornell Medical College

New York, New York, 10021, United States

Location

MD Anderson Cancer Center, Department of Leukemia

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 27479177 DERIVED

MeSH Terms

Conditions

Primary Myelofibrosis; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Polycythemia Vera; Thrombocythemia, Essential

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Hemorrhagic Disorders

Results Point of Contact

• Title: Medical Affairs
• Organization: NS Pharma, Inc.

trialinfo@nspharma.com

201-986-3860

Study Officials

• Srdan Verstovsek, M.D., Ph.D.

  MD Anderson Cancer Center, Houston, TX, 77030

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1: 75, 125, 200, 300, 400 mg QD and 100, 200, 250, 300, 400 mg BID Phase 2: 300 mg QD

Study Record Dates

• First Submitted: August 15, 2011
• First Posted: August 26, 2011
• Study Start: June 1, 2011
• Primary Completion: April 22, 2020
• Study Completion: April 22, 2020
• Last Updated: March 9, 2022
• Results First Posted: March 9, 2022

Record last verified: 2022-02

Locations

US (9)