Myeloproliferative Neoplasms Clinical Trial

A Trial of Fedratinib in Subjects With DIPSS, Intermediate or High-Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis and Previously Treated With Ruxolitinib

Summary

This is Single-Arm, Open-Label Efficacy and Safety Trial of Fedratinib in Subjects with DIPSS (Dynamic International Prognostic Scoring System)-Intermediate or High- Risk Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (post-PV MF), or Post-Essential Thrombocythemia Myelofibrosis (post-ET MF) and Previously Treated with Ruxolitinib.

The primary objective of the study is to evaluate the percentage of subjects with at least a 35% reduction in spleen size and one of the secondary objectives is to evaluate the safety of fedratinib.

View Full Description

Full Description

This is Single-Arm, Open-Label Efficacy and Safety Trial of Fedratinib in Subjects with DIPSS (Dynamic International Prognostic Scoring System)-Intermediate or High- Risk Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (post-PV MF), or Post-Essential Thrombocythemia Myelofibrosis (post-ET MF) and Previously Treated with Ruxolitinib.

The spleen volume reduction at the end of Cycle 6 as the primary objective. The secondary objectives of the study are to further evaluate the safety and to assess and implement mitigation strategies for WE and for gastrointestinal (GI) adverse events.

The study will be at multiple centers to provide access to a broad population and have assurance the results are likely to have general applicability.

This is also conducted as an open-label study to collect efficacy and safety data with fedratinib use, no randomization or stratification will occur.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Main Study Inclusion Criteria

Subject is at least 18 years of age at the time of signing the informed consent form (ICF)
Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Score (PS) of 0, 1 or 2
Subject has diagnosis of primary myelofibrosis (PMF) according to the 2016 World Health Organization (WHO) criteria, or diagnosis of post-ET or post-PV myelofibrosis according to the IWG-MRT 2007 criteria, confirmed by the most recent local pathology report
Subject has a DIPSS Risk score of Intermediate or High
Subject has a measurable splenomegaly during the screening period as demonstrated by spleen volume of ≥ 450 cm3 by MRI or CT-scan assessment or by palpable spleen measuring ≥ 5 cm below the left costal margin.

Subject has been previously exposed to ruxolitinib, while diagnosed with MF (PMF, post-ET MF or post-PV MF), and must meet at least one of the following criteria (a or b)

Treatment with ruxolitinib for ≥ 3 months

Treatment with ruxolitinib for ≥ 28 days complicated by any of the following:

Development of a red blood cell transfusion requirement (at least 2 units/month for 2 months) or
Grade ≥ 3 AEs of thrombocytopenia, anemia, hematoma, and/or hemorrhage while on treatment with ruxolitinib
Subject must have treatment-related toxicities from prior therapy resolved to Grade 1 or pretreatment baseline before start of last therapy prior to fedratinib treatment.
Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted
Subject is willing and able to adhere to the study visit schedule and other protocol requirements
Participants must agree to use effective contraception

Exclusion Criteria:

Main Study Exclusion Criteria

Any of the following laboratory abnormalities:

Platelets < 50,000/μL
Absolute neutrophil count (ANC) < 1.0 x 109/L
White blood count (WBC) > 100 x 10^9/L
Myeloblasts > 5 % in peripheral blood
Estimated glomerular filtration rate < 30 mL/min/1.73 m^2 (as per the Modification of Diet in Renal Disease [MDRD] formula)
Serum amylase or lipase > 1.5 x ULN (upper limit of normal)
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 x ULN
Total bilirubin > 1.5 x ULN, subject's total bilirubin between 1.5 - 3.0 x ULN are eligible if the direct bilirubin fraction is < 25% of the total bilirubin
Subject is pregnant or lactating female
Subject with previous splenectomy
Subject with previous or planned hematopoietic cell transplant
Subject with prior history of encephalopathy, including Wernicke's
Subject with signs or symptoms of encephalopathy including Wernicke's (eg, severe ataxia, ocular paralysis or cerebellar signs)
Subject with thiamine deficiency, defined as thiamine levels in whole blood below normal range according to institutional standard and not corrected prior to enrollment on the study
Subject with concomitant treatment with or use of pharmaceutical, herbal agents or food known to be strong or moderate inducers of Cytochrome P450 3A4 (CYP3A4), or dual CYP2C19 and CYP3A4 inhibitors
Subject on any chemotherapy, immunomodulatory drug therapy (eg, thalidomide, interferon-alpha), anagrelide, immunosuppressive therapy, systemic corticosteroids > 10 mg/day prednisone or equivalent. Subjects who have had prior exposure to hydroxyurea (eg, Hydrea) in the past may be enrolled into the study as long as it has not been administered within 14 days prior to the start of fedratinib treatment
Subject has received ruxolitinib within 14 days prior to the start of fedratinib
Subject on treatment with myeloid growth factor (eg, granulocyte-colony stimulating factor [G-CSF]) within 14 days prior to the start of fedratinib treatment
Subject with previous exposure to Janus kinase (JAK) inhibitor(s) for more than 1 cycle other than ruxolitinib treatment
Subject on treatment with aspirin with doses > 150 mg daily
Subject with major surgery within 28 days before starting fedratinib treatment
Subject with diagnosis of chronic liver disease (eg, chronic alcoholic liver disease, autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis, hemochromatosis, non-alcoholic steatohepatitis)

Subject with prior malignancy other than the disease under study unless the subject has not required treatment for the malignancy for at least 3 years prior to enrollment.

However, subject with the following history/concurrent conditions provided successfully treated may enroll: non-invasive skin cancer, in situ cervical cancer, carcinoma in situ of the breast, incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical staging system), or is free of disease and on hormonal treatment only

Subject with uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4)
Subject with known human immunodeficiency virus (HIV), known active infectious Hepatitis B (HepB), and/or known active infectious Hepatitis C (HepC)
Subject with serious active infection
Subject with presence of any significant gastric or other disorder that would inhibit absorption of oral medication
Subject is unable to swallow capsule
Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study
Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
Subject has any condition that confounds the ability to interpret data from the study
Subject with participation in any study of an investigational agent (drug, biologic, device) within 30 days prior to start of fedratinib treatment
Subject with life expectancy of less than 6 months.

Study is for people with:

Myeloproliferative Neoplasms

Phase:

Phase 3

Estimated Enrollment:

38

Study ID:

NCT03755518

Recruitment Status:

Active, not recruiting

Sponsor:

Celgene

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There are 35 Locations for this study

See Locations Near You

University of Colorado Cancer Center
Aurora Colorado, 80045, United States
Baptist Health - Miami Cardiac & Vascular Institute
Miami Florida, 33176, United States
Augusta University - Georgia Cancer Center
Augusta Georgia, 30912, United States
Rush University Medical Center - University Cardiovascular Surgeons
Chicago Illinois, 60612, United States
The University of Chicago Medical Center - Duchossois Center for Advanced Medicine
Chicago Illinois, 60637, United States
Advocate Medical Group
Park Ridge Illinois, 60068, United States
University of Kansas Medical Center
Kansas City Kansas, 66160, United States
St. Agnes - Medical Center
Baltimore Maryland, 21229, United States
Center for Cancer and Blood Disorders, P.C.
Bethesda Maryland, 20817, United States
Local Institution - 118
Bethesda Maryland, 20817, United States
Maryland Oncology Hematology PA
Columbia Maryland, 21044, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor Michigan, 48109, United States
Washington Univ School of Medicine
Saint Louis Missouri, 63110, United States
Newark Beth Israel Medical Center
Newark New Jersey, 07112, United States
Brookdale University Hospital and Medical Center
Brooklyn New York, 11212, United States
Icahn School of Medicine at Mount Sinai
New York New York, 10029, United States
Columbia University Medical Center
New York New York, 10032, United States
SUNY Upstate Medical University
Syracuse New York, 13210, United States
North Carolina Women's Hospital
Chapel Hill North Carolina, 27514, United States
Duke University Medical Center
Durham North Carolina, 27705, United States
UC Health Barrett Cancer Center
Cincinnati Ohio, 45219, United States
Local Institution - 106
Pittsburgh Pennsylvania, 15224, United States
Western Pennsylvania Cancer Institute
Pittsburgh Pennsylvania, 15224, United States
Avera Cancer Institute
Sioux Falls South Dakota, 57105, United States
Local Institution - 119
Dallas Texas, 75390, United States
UT Southwestern Medical Center Simmons Comprehensive Cancer Center
Dallas Texas, 75390, United States
Texas Oncology- Fort Worth Cancer Center
Fort Worth Texas, 76104, United States
The University of Texas MD Anderson Cancer Center
Houston Texas, 77303, United States
UT Health - San Antonio
San Antonio Texas, 78229, United States
Fred Hutchinson Cancer Research Center
Seattle Washington, 98109, United States
University of Wisconsin Medical School
Madison Wisconsin, 53792, United States
Providence Hematology
Vancouver British Columbia, V6Z 2, Canada
London Health Sciences Centre
London Ontario, N6C 6, Canada
Ottawa Hospital
Ottawa Ontario, K1H 8, Canada
Local Institution - 200
Toronto Ontario, M5G 2, Canada
Princess Margaret Hospital University Health Network
Toronto Ontario, M5G 2, Canada
Hopital Maisonneuve-Rosemont
Montreal Quebec, H1T 2, Canada
Jewish General Hospital
Montreal Quebec, H3T 1, Canada
Local Institution - 202
Montreal Quebec, H3T 1, Canada
CIUSSS de l'Estrie - CHUS
Sherbrooke Quebec, J1K 2, Canada

How clear is this clinincal trial information?

Study is for people with:

Myeloproliferative Neoplasms

Phase:

Phase 3

Estimated Enrollment:

38

Study ID:

NCT03755518

Recruitment Status:

Active, not recruiting

Sponsor:


Celgene

How clear is this clinincal trial information?

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