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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 06/01/2020.

An Efficacy and Safety 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

Clinicaltrials.gov identifier NCT03755518

Recruitment Status Recruiting

First Posted November 28, 2018

Last update posted April 7, 2020

Study Description

Brief 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 of spleen volume and one of the secondary objectives is to evaluate the safety of fedratinib

  • Condition or Disease:Primary Myelofibrosis
    Post-Polycythemia Vera
    Myelofibrosis
  • Intervention/Treatment: Drug: FEDRATINIB
  • Phase: Phase 3
Detailed Description

N/A

Study Design
  • Study Type: Interventional
  • Estimated Enrollment: 110 participants
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label) ()
  • Primary Purpose: Treatment
  • Official Title: A Phase 3b, Multicenter, Single-arm, Open-label Safety AND Efficacy Study of Fedratinib in Subjects With DIPSS-Intermediate or High-Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis
  • Actual Study Start Date: March 2019
  • Estimated Primary Completion Date: May 2022
  • Estimated Study Completion Date: November 2023
Arms and interventions
Arm Intervention/treatment
Experimental: Administration of Fedratinib 400mg/day
Self-administered Investigational Product (IP) (400 mg/day) on an outpatient basis, once daily preferably with food during an evening meal at the same time each day in consecutive 4-week (28-day) cycles.
Drug: FEDRATINIB
A potent and selective inhibitor of JAK2 kinase activity
Outcome Measures
  • Primary Outcome Measures: 1. Proportion of subjects who have a ≥ 35% SVR at end of Cycle 6 [ Time Frame: At the end of Cycle 6 (each cycle is 28 days) ]
    Spleen volume response rate (RR)
  • Secondary Outcome Measures: 1. Adverse Event(s) [ Time Frame: Up to 12 months post last dose ]
    Number of participants with adverse event
  • 2. Proportion of subjects who have ≥ 50% reduction in spleen size by [ Time Frame: At the end of Cycle 6 (each cycle is 28 days) ]
    Spleen response rate by palpation (RRP)
  • 3. Symptom response rate (SRR) [ Time Frame: At the end of Cycle 6 (each cycle is 28 days) ]
    Is defined as the proportion of subjects with ≥ 50% reduction from baseline to the end of Cycle 6 in total symptom score (TSS) measured by MFSAF version 4.0.
  • 4. To evaluate durability of spleen volume response (DR) [ Time Frame: From enrollment until treatment discontinuation (estimation of 12 months) ]
    Is defined as time from the first documented spleen response (ie, ≥ 35% reduction in spleen volume) to the first documented spleen volume reduction < 35%.
  • 5. To evaluate the durability of spleen response by palpation (DRP) [ Time Frame: From enrollment until treatment discontinuation (estimation of 12 months) ]
    Is defined as time from the first documented palpable spleen response, according to the IWG-MRT 2013 to the time of the first documented loss of response according to the IWG-MRT 2013.
  • 6. Durability of symptoms response (DSR) [ Time Frame: Up to 30 days post last dose ]
    Is defined as time from the first documented response in TSS (ie, reduction in TSS ≥ 50%) measured by MFSAF version 4.0 to the first documented TSS reduction < 50%.
  • 7. Gastrointestinal Adverse Events [ Time Frame: Up to 30 days post last dose ]
    Incidence of subjects with Grade 3 or higher Gastrointestinal events (nausea, diarrhea, or vomiting) according to CTCAE v5.0
  • 8. Wernicke encephalopathy (WE) events [ Time Frame: Up to 30 days post last dose ]
    Occurrence of confirmed Wernicke encephalopathy events
  • 9. Wernicke encephalopathy (WE) thiamine monitoring [ Time Frame: Up to 30 days post last dose ]
    Monitoring and correction of thiamine levels as appropriate
Eligibility Criteria
  • Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:

1. Subject is at least 18 years of age at the time of signing the informed consent form
(ICF)

2. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Score (PS) of 0,
1 or 2

3. 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

4. Subject has a DIPSS Risk score of Intermediate or High

5. 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

6. Subject has been previously exposed to ruxolitinib, and must meet at least one of the
following criteria (a or b)

a. Treatment with ruxolitinib for ≥ 3 months b. 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

7. 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.

8. Subject must understand and voluntarily sign an ICF prior to any study-related
assessments/procedures being conducted

9. Subject is willing and able to adhere to the study visit schedule and other protocol
requirements

10. A female of childbearing potential (FCBP) must:

1. Have two negative pregnancy tests as verified by the Investigator prior to
starting study therapy. She must agree to ongoing pregnancy testing during the
course of the study, and after end of study therapy. This applies even if the
subject practices true abstinence* from heterosexual contact.

2. Either commit to true abstinence* from heterosexual contact (which must be
reviewed on a monthly basis and source documented) or agree to use, and be able
to comply with acceptable effective contraception** without interruption, -14
days prior to starting investigational product, during the study therapy
(including dose interruptions), and for 30 days after discontinuation of study
therapy.

Note: A female of childbearing potential (FCBP) is a female who: 1) has achieved
menarche at some point, 2) has not undergone a hysterectomy or bilateral
oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following
cancer therapy does not rule out childbearing potential) for at least 24
consecutive months (ie has had menses at any time in the preceding 24 consecutive
months).

11. Male subjects must:

1. Practice true abstinence* (which must be reviewed on a monthly basis) or agree to
use a condom during sexual contact with a pregnant female or a female of
childbearing potential while participating in the study, during dose
interruptions and for at least 30 days following investigational product
discontinuation, or longer if required for each compound and/or by local
regulations, even if he has undergone a successful vasectomy.

- True abstinence is acceptable when this is in line with the preferred and
usual lifestyle of the subject. [Periodic abstinence (eg, calendar,
ovulation, symptothermal, post-ovulation methods) and withdrawal are not
acceptable methods of contraception].

- Agreement to use highly effective methods of contraception that alone
or in combination result in a failure rate of a Pearl index of less
than 1% per year when used consistently and correctly throughout the
course of the study. Such methods include: Combined (estrogen and
progestogen containing) hormonal contraception: Oral; Intravaginal;
Transdermal; Progestogen-only hormonal contraception associated with
inhibition of ovulation: Oral; Injectable hormonal contraception;
Implantable hormonal contraception; Placement of an intrauterine
device; Placement of an intrauterine hormone-releasing system;
Bilateral tubal occlusion; Vasectomized partner.

Exclusion Criteria:

1. Any of the following laboratory abnormalities:

1. Platelets < 50,000/μL 2. Absolute neutrophil count (ANC) < 1.0 x 109/L 3. Myeloblasts ≥ 5 % in peripheral blood 4. Serum creatinine clearance 1.5 x ULN (upper limit of normal)

6. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 x ULN

7. 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
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

10. Subject has received ruxolitinib within 14 days prior to the start of fedratinib

11. Subject on treatment with myeloid growth factor (eg, granulocyte-colony stimulating
factor [G-CSF]) within 14 days prior to the start of fedratinib treatment

12. Subject with previous exposure to Janus kinase (JAK) inhibitor(s) other than
ruxolitinib treatment

13. Subject on treatment with aspirin with doses > 150 mg daily

14. Subject with major surgery within 28 days before starting fedratinib treatment

15. Subject with diagnosis of chronic liver disease (eg, chronic alcoholic liver disease,
autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis,
hemochromatosis, non-alcoholic steatohepatitis)

16. 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

17. Subject with uncontrolled congestive heart failure (New York Heart Association
Classification 3 or 4)

18. Subject with known human immunodeficiency virus (HIV), known active infectious
Hepatitis B (HepB), and/or known active infectious Hepatitis C (HepC)

19. Subject with serious active infection

20. Subject with presence of any significant gastric or other disorder that would inhibit
absorption of oral medication

21. Subject is unable to swallow capsule

22. Subject has any significant medical condition, laboratory abnormality, or psychiatric
illness that would prevent the subject from participating in the study

23. 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

24. Subject has any condition that confounds the ability to interpret data from the study

25. Subject with participation in any study of an investigational agent (drug, biologic,
device) within 30 days prior to start of fedratinib treatment

Contacts and Locations
Contacts

Contact: Daniel Aversa, MS 908.499.9666 daversa@celgene.com

Locations
Show 35 Study Locations
Sponsors and Collaborators

Celgene

Impact Biomedicines, Inc., a wholly owned subsidiary of Celgene Corporation

Investigators

Study Director: Daniela Buglio, MD Celgene

More Information
  • Responsible Party: Celgene
  • ClinicalTrials.gov Identifier: NCT03755518 History of Changes
  • Other Study ID Numbers: FEDR-MF-001, U1111-1223-2862, 2018-002237-38
  • First Posted: November 28, 2018 Key Record Dates
  • Last Update Posted: April 7, 2020
  • Last Verified: April 2020
  • Studies a U.S. FDA-regulated Drug Product: Yes
  • Studies a U.S. FDA-regulated Device Product: No
  • Keywords provided by Celgene: Myelofibrosis (MF)
    Primary Myelofibrosis (PMF)
    Post-Polycythemia vera (Post-PV)
    Post-essential thrombocythemia (Post-ET)
    Myeloproliferative neoplasms (MPN)
  • Additional relevant MeSH terms: Polycythemia Vera
    Primary Myelofibrosis
    Polycythemia
    Thrombocytosis
    Thrombocythemia, Essential