A Study of Fedratinib With IDH Inhibition in Advanced-Phase IDH-Mutated Ph-Negative Myeloproliferative Neoplasms

  • STATUS
    Recruiting
  • End date
    Oct 1, 2025
  • participants needed
    50
  • sponsor
    University of Chicago
Updated on 29 November 2021
cancer
myeloid leukemia
myelofibrosis
hydroxyurea
leukemia
blast cells

Summary

The purpose of this research is to gather information on the safety and effectiveness of fedratinib (a drug called a "jak inhibitor" ) in combination with ivosidenib or enasidenib (two anti-cancer drugs). While all three drugs are FDA-approved for various conditions, the US Food and Drug Administration (FDA) has not approved the combination of these drugs for the treatment of rare blood cancers that present Isocitrate dehydrogenase (IDH) mutations, and therefore these drugs can only be given in a research study.

Description

Doctors leading this study hope to learn about the safety of combining fedratinib (a type of drug called a "JAK inhibitor" whichblocks the activity of janus kinase enzymes in your body) with anti-cancer drugs ivosidenib and enasidenib in participants who have rare blood cancers that show Isocitrate dehydrogenase (IDH) mutations (a type of genetic mutation). Your participation in this research will last about 24 months.

The purpose of this research is to gather information on the safety and effectiveness of fedratinib in combination with ivosidenib or enasidenib. While all three drugs are FDA-approved for various conditions, the US Food and Drug Administration (FDA) has not approved the combination of these drugs for the treatment of IDH-mutated blood cancers (known as myeloproliferative neoplasms), and therefore these drugs can only be given in a research study.

Details
Condition haematological malignancy, myeloproliferative disorders, IDH2 Gene Mutation, Leukemia (Pediatric), hematologic malignancies, Myeloproliferative Neoplasms, Leukemia, hematological tumor, IDH Mutation, leukemia, hematological malignancy, Hematologic Cancer, Hematologic Malignancy, IDH1 Mutation, myeloproliferative neoplasm, Non-Hodgkin's Lymphoma, Multiple Myeloma, MYELOPROLIFERATIVE DISORDER, Hematologic Neoplasms, hematological malignancies, Lymphoma, Blood Cancer
Treatment Enasidenib, Ivosidenib, FEDRATINIB
Clinical Study IdentifierNCT04955938
SponsorUniversity of Chicago
Last Modified on29 November 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Must be diagnosed with advanced-Phase IDH-mutated Ph-neg MPNs (both untreated
and relapsed/refractory) including any of the following
polycythemia vera with (PV) 5% blasts
essential thrombocythemia (ET) with 5% blasts
primary myelofibrosis (PMF) with 5% blasts
Atypical CML with 5% blasts
MPN-NOS with 5% blasts
MDS/MPN Overlap Syndromes with 5% blasts including CMML
post-PV myelofibrosis with 5% blasts
post-ET myelofibrosis with 5% blasts
Patients can be on cytoreduction at time of study enrollment with hydroxyurea or steroids
Age 18 years. Because no dosing or adverse event data are currently available on the use of fedratinib in combination with IDH inhibitors in patients <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
Eastern Cooperative Oncology Group performance status 2 (see Appendix A)
Patients must have normal organ and marrow function as defined below
Creatinine clearance 30 mL/min, determined by the Cockroft-Gault formula, OR serum creatinine 1.5 x ULN
AST and ALT 3 x ULN and bilirubin 1.5 x ULN (unless considered due to Gilbert's syndrome, leukemic involvement, or extravascular hemolysis in the spleen)
Other eligibility criteria includes the following
Patients must be at least 2 weeks from major surgery, radiation therapy, or participation in other investigational trials, and must have recovered from clinically significant toxicities related to these prior treatments
Female patients of childbearing potential must have negative results for a pregnancy test
Patients must be willing to use appropriate contraception. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

Patients cannot be on concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in this protocol. Patients cannot have had prior treatment with an IDH1 inhibitor, IDH2 inhibitor, or fedratinib
Patients with a "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for 3 years or they are not currently requiring treatment for an indolent malignancy
Patients with prior history of encephalopathy, including Wernicke's (WE). If a patient has signs/symptoms of encephalopathy, including WE (eg severe ataxia, ocular paralysis or cerebellar signs) in which case thiamine deficiency needs to be excluded and a brain MRI might be required to exclude possible Wernicke's encephalopathy. Patients with thiamine deficiency that has not been corrected before proceeding to the dose finding phase of the study
History of allergic reactions attributed to compounds of similar chemical or biologic composition to fedratinib, ivosidenib, or enasidenib
Patients receiving any medications or substances that are inhibitors or inducers of CYP3A4 should have eligibility and alternative medications reviewed by site PI. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as <http://medicine.iupui.edu/clinpharm/ddis/table.aspx>; medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active chronic liver disease (eg chronic alcoholic liver disease, autoimmune hepatitis, sclerosing cholangitis, primary biliary cholangitis, hemochromatosis) or psychiatric illness/social situations that would limit compliance with study requirements
Subject has a history of progressive multifocal leukoencephalopathy (PML)
Subject has QTc interval (ie, Fridericia's correction [QTcF]) 450 msec or other factors that increase the risk of QT prolongation or arrhythmic events (e.g. family history of long QT interval syndrome) at screening unless due to bundle branch block or pacemaker with approval of the principal investigator
Pregnant women are excluded from this study because fedratinib, ivosidenib, and enasidenib carry the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with fedratinib, ivosidenib, and enasidenib, breastfeeding should be discontinued if the mother is treated with any of these agents
HIV-positive patients, patients with active hepatitis B, and patients with active Hepatitis C on antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with fedratinib, ivosidenib, and enasidenib. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
Patient is known to have dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally
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