- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05524857
Combination of Fedratinib and Decitabine for Myeloproliferative Neoplasms (MPN)- Accelerated Phase (AP)/Blast Phase (BP)
April 19, 2024 updated by: Joseph Jurcic
Phase I Trial of Fedratinib in Combination With Decitabine in Patients With Myeloproliferative Neoplasms in Accelerated and Blast Phase
The purpose of this research is to study the safety and tolerability and to establish the maximum tolerated dose (MTD) of the combination of two drugs, fedratinib and decitabine, for the treatment of advanced-phase MPNs.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Detailed Description
This is a single center phase I dose-escalation trial of Fedratinib in Combination with Decitabine in Patients with Myeloproliferative Neoplasms.
The primary objective is to determine the maximum tolerated dose of the combination therapy, using a 3+3 dose escalation algorithm.
Fedratinib will be administered at 2 dose levels: 300 mg and 400 mg by mouth, once daily.
Fedratinib will be administered concomitantly with decitabine 20 mg/m2 intravenously over 1 hour per day for 5 days in 28-day cycles.
Study Type
Interventional
Enrollment (Actual)
2
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
New York
-
New York, New York, United States, 10032
- New York Presbyterian Hospital/Columbia University Irving Medical Center
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Subjects must have MPN-AP as defined by 10%-19% blasts in the peripheral blood or bone marrow and evidence of dysplastic marrow features with a concomitant diagnosis of essential thrombocythemia (ET), polycythemia vera (PV) or primary myelofibrosis (PMF) or a diagnosis of MPN-BP as defined by 20% blasts in the blood or bone marrow following a previous diagnosis of ET, PV or PMF.
Subjects must have adequate organ function documented within 14 days of study entry as follows:
- Estimated creatinine clearance (by Cockcroft-Gault Equation) of ≥ 50 mL/min
- Serum total bilirubin ≤ 1.5 × ULN (unless attributable to Gilbert's disease or hemolysis, in which case the direct bilirubin level must be ≤ 1.5 × upper limit of normal (ULN)).
- Alkaline phosphatase, serum aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤ 2.5 × ULN.
- ≥ 18 years of age.
- Eastern Cooperative Oncology Group (ECOG) Performance status of 0-2. Patients with ECOG performance status of 3 will be eligible if the lower performance status is deemed by the investigator to be due entirely to MPN-AP/BP and not due to another comorbidity.
Exclusion Criteria:
- Receipt of chemotherapy or investigational therapy, with the exception of hydroxyurea, within 4 weeks of study entry. Previous treatment at any time with decitabine, fedratinib or ruxolitinib as single agents will not exclude eligibility. Previous stem cell transplant will not exclude eligibility as long as other inclusion/exclusion criteria have been met and subjects do not have Grade ≥ II graft-versus-host disease (GVHD) requiring systemic immunosuppressive therapy.
- Subjects with an Human leukocyte antigen (HLA)-compatible donor or stem cell source who are immediate candidates for allogeneic hematopoietic cell transplantation (HCT).
- Subjects who are receiving any concurrent treatment for acute myeloid leukemia (AML), including other investigational agents.
- Diagnosis of acute myelofibrosis.
- Uncontrolled intercurrent illness including, but not limited to hepatitis, human immunodeficiency virus (HIV)-positive subjects receiving combination antiretroviral therapy, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class 3 or 4), unstable angina pectoris, ventricular arrhythmia, Child-Pugh Class C cirrhosis, or psychiatric illness/social situations that would limit compliance with study requirements.
- Subjects with a prior history of Wernicke's encephalopathy (WE) will be excluded. If a subject has signs or symptoms of encephalopathy, including Wernicke's encephalopathy (e.g. severe ataxia, ocular paralysis or cerebellar signs), thiamine deficiency must be excluded and a brain MRI should be obtained prior to study initiation to evaluate for WE.
- Other medications, severe acute/chronic medical or psychiatric conditions, or laboratory abnormalities that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, that in the judgment of the Investigator would make the subject inappropriate for entry into this study.
- Pregnant women are excluded because of the potential for teratogenic or abortifacient effects.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Fedratinib 300 mg
Cohort 1: 300 mg of Fedratinib by mouth, once daily during each 28-day cycle
|
300 mg by mouth, once daily
Other Names:
20 mg/m2 for injection, for intravenous use
Other Names:
|
Experimental: Fedratinib 400 mg
Cohort 2: 400 mg of Fedratinib by mouth, once daily during each 28-day cycle
|
20 mg/m2 for injection, for intravenous use
Other Names:
400 mg by mouth, once daily
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Tolerated Dose (MTD) of Decitabine and Fedratinib
Time Frame: Up to 8 weeks for each dosing cohort
|
The MTD will be determined using a 3+3 algorithm.
If < 33% of the subjects enrolled at a dose level experience a dose-limiting toxicity (DLT), escalation to the next designated dose cohort will continue.
If ≥ 33% of the subjects enrolled at a dose level experience a DLT, the previous dosing cohort will be considered the MTD.
DLT is defined as: (1) Grade 3, 4, or 5 non-hematologic toxicity considered at least possibly related to the study drug, except for infection, bleeding, fever, fatigue, dyspnea, and (2) Grade 3, 4, or 5 anemia, neutropenia or thrombocytopenia with a hypocellular bone marrow and < 5% marrow blasts lasting for 42 days or more.
|
Up to 8 weeks for each dosing cohort
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Complete Remission (CR) Rate
Time Frame: Up to 3 years
|
Complete remission defined as participants that are free of all symptoms related to leukemia and have an absolute neutrophil count ≥ 1 x 10^9/L, no need for red blood cell transfusion, platelet count ≥ 100 x 10^9/L, and normal marrow differential (≤ 5 % blasts) in a normo- or hypercellular marrow.
|
Up to 3 years
|
Composite Complete Remission (CRc) Rate
Time Frame: Up to 3 years
|
CRc defined as (CR + Complete remission with incomplete count recovery (CRi)).
CRi defined as CR but incomplete count recovery (absolute neutrophil count < 1000/microL or platelet count < 100,000/micro/L).
|
Up to 3 years
|
Partial Remission (PR) Rate
Time Frame: Up to 3 years
|
PR defined as CR with 6 - 25 % abnormal cells in the marrow or 50 % decrease in bone marrow blasts.
|
Up to 3 years
|
Progression Free Survival (PFS)
Time Frame: Up to 3 years
|
PFS is defined as the duration of time from entry on study to time of recurrence, flow cytometric relapse, cytogenetic relapse, molecular relapse, or death, whichever occurs first.
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Up to 3 years
|
Overall Survival (OS)
Time Frame: Up to 3 years
|
OS is defined as the duration of time from entry on study to time of death from any cause.
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Up to 3 years
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Joseph Jurcic, MD, Columbia University
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
January 28, 2022
Primary Completion (Actual)
April 9, 2024
Study Completion (Actual)
April 9, 2024
Study Registration Dates
First Submitted
August 30, 2022
First Submitted That Met QC Criteria
August 30, 2022
First Posted (Actual)
September 1, 2022
Study Record Updates
Last Update Posted (Actual)
April 23, 2024
Last Update Submitted That Met QC Criteria
April 19, 2024
Last Verified
April 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Disease Attributes
- Bone Marrow Diseases
- Hematologic Diseases
- Neoplastic Processes
- Leukemia
- Cell Transformation, Neoplastic
- Carcinogenesis
- Leukemia, Myeloid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Chronic Disease
- Neoplasms
- Blast Crisis
- Myeloproliferative Disorders
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Decitabine
Other Study ID Numbers
- AAAT9407
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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