Combination of Fedratinib and Decitabine for Myeloproliferative Neoplasms (MPN)- Accelerated Phase (AP)/Blast Phase (BP)

NCT ID: NCT05524857

Last Updated: 2024-04-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-28
• Study Completion Date: 2024-04-09

Brief Summary

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.

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.

Conditions

Myeloproliferative Neoplasm

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Fedratinib 300 mg

Cohort 1: 300 mg of Fedratinib by mouth, once daily during each 28-day cycle

Group Type: EXPERIMENTAL

Fedratinib Oral Capsule 300 mg

Intervention Type: DRUG

300 mg by mouth, once daily

Decitabine 20 mg/m2

Intervention Type: DRUG

20 mg/m2 for injection, for intravenous use

Fedratinib 400 mg

Cohort 2: 400 mg of Fedratinib by mouth, once daily during each 28-day cycle

Group Type: EXPERIMENTAL

Decitabine 20 mg/m2

Intervention Type: DRUG

20 mg/m2 for injection, for intravenous use

Fedratinib Oral Capsule 400 mg

Intervention Type: DRUG

400 mg by mouth, once daily

Interventions

Fedratinib Oral Capsule 300 mg

300 mg by mouth, once daily

Intervention Type: DRUG

Decitabine 20 mg/m2

20 mg/m2 for injection, for intravenous use

Intervention Type: DRUG

Fedratinib Oral Capsule 400 mg

400 mg by mouth, once daily

Intervention Type: DRUG

Other Intervention Names

Inrebic; Dacogen; Inrebic

Eligibility Criteria

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:

1. Estimated creatinine clearance (by Cockcroft-Gault Equation) of ≥ 50 mL/min

2. 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)).

3. 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

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Joseph Jurcic

OTHER

Sponsor Role: lead

Responsible Party

Joseph Jurcic

Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Joseph Jurcic, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

New York Presbyterian Hospital/Columbia University Irving Medical Center

New York, New York, United States

Countries

United States

Other Identifiers

AAAT9407

Identifier Type: -

Identifier Source: org_study_id