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

NCT05524857 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: AAAT9407
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Myeloproliferative Neoplasm

Keywords

Blast Phase; Fedratinib; Decitabine

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Decitabine and Fedratinib

  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 Outcomes (5)

• Complete Remission (CR) Rate

  Up to 3 years

• Composite Complete Remission (CRc) Rate

  Up to 3 years

• Partial Remission (PR) Rate

  Up to 3 years

• Progression Free Survival (PFS)

  Up to 3 years

• Overall Survival (OS)

  Up to 3 years

Study Arms (2)

Fedratinib 300 mg

EXPERIMENTAL

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

Drug: Fedratinib Oral Capsule 300 mg; Drug: Decitabine 20 mg/m2

Fedratinib 400 mg

EXPERIMENTAL

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

Drug: Decitabine 20 mg/m2; Drug: Fedratinib Oral Capsule 400 mg

Interventions

Fedratinib Oral Capsule 300 mg DRUG

300 mg by mouth, once daily

Also known as: Inrebic

Fedratinib 300 mg

Decitabine 20 mg/m2 DRUG

20 mg/m2 for injection, for intravenous use

Also known as: Dacogen

Fedratinib 300 mg; Fedratinib 400 mg

Fedratinib Oral Capsule 400 mg DRUG

400 mg by mouth, once daily

Also known as: Inrebic

Fedratinib 400 mg

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Joseph Jurcic: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

New York Presbyterian Hospital/Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Myeloproliferative Disorders; Blast Crisis

Interventions

fedratinib; Decitabine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Joseph Jurcic, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: August 30, 2022
• First Posted: September 1, 2022
• Study Start: January 28, 2022
• Primary Completion: April 9, 2024
• Study Completion: April 9, 2024
• Last Updated: April 23, 2024

Record last verified: 2024-04

Locations

US (1)