RECRUITING

Ivosidenib and Ruxolitinib in Patients With Advanced Myeloproliferative Neoplasms (MPNs) That Have an IDH1 Gene Mutation

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this research is to gather information on the safety and effectiveness determining maximum tolerated dose (MTD) of ruxolitinib in combination with ivosidenib in IDH1-mutated advanced-phase Ph-negative MPNs while evaluate the efficacy of ruxolitinib in combination with ivosidenib in IDH1-mutated advanced-phase Ph-negative MPNs.

Official Title

A Phase 1b Trial of Ivosidenib Combined With Ruxolitinib in IDH1-Mutated Advanced-Phase MPNs

Quick Facts

Study Start:2024-09-19

Study Completion:2026-05

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06291987

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.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:Yes

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Advanced-Phase IDH1-mutated Ph-negative MPNs (both untreated and relapsed/refractory) including any of the following: * polycythemia vera with (PV) ≥ 5% peripheral or bone marrow blasts at time of screening * essential thrombocythemia (ET) with ≥ 5% peripheral or bone marrow blasts at time of screening * primary myelofibrosis (PMF) with ≥ 5% peripheral or bone marrow blasts at time of screening * Atypical CML with ≥ 5% peripheral or bone marrow blasts at time of screening * MPN-NOS with ≥ 5% peripheral or bone marrow blasts at time of screening * MDS/MPN Overlap Syndromes including CMML with ≥ 5% peripheral or bone marrow blasts at time of screening * post-PV myelofibrosis with ≥ 5% blasts peripheral or bone marrow blasts at time of screening * post-ET myelofibrosis with ≥ 5% blasts peripheral or bone marrow blasts at time of screening * primary and secondary myelofibrosis with inadequate response to JAK inhibitor regardless of blast percentage. Inadequate response to JAK inhibitor will be defined as lack of achieving any clinical improvement criteria within 12 weeks of of JAK inhibitor initiation. * Patients can be on cytoreduction at time of study enrollment with hydroxyurea or steroids. * Age ≥18 years. * ECOG performance status ≤2 * Patients must have normal organ and marrow function as defined below: * Creatinine clearance ≥60 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) * A platelet count of 50 x 109/L should be met for those with chronic-phase myelofibrosis and \< 5% blasts peripherally or in bone marrow * HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. * Other eligibility criteria include the following: * Patients must be at least 4 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. * The effects of the investigational agents on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. * Ability to understand and the willingness to sign a written informed consent document.	* Patients cannot be on concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in this protocol. Patients cannot have had prior treatment with ivosidenib. * 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 or they are not currently requiring treatment for an indolent malignancy. Patients with APL and active CNS disease would also be excluded * History of allergic reactions attributed to compounds of similar chemical or biologic composition to ivosidenib or ruxolitinib. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, venous thromboembolism, stroke, 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 QTc interval ≥ 450 msec or other factors that increase the risk of QT prolongation or arrhythmic events at screening unless due to bundle branch block or pacemaker with approval of the principal investigator. * Pregnant women are excluded from this study because ruxolitinib and ivosidenib 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 ruxolitinib and ivosidenib, breastfeeding should be discontinued if the mother is treated with any of these agents. * Patient is known to have dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally. * Patients receiving any medications or substances that are inhibitors or inducers of CYP3A4 should have eligibility and alternative medications reviewed by site PI.

Inclusion Criteria

Exclusion Criteria

* Advanced-Phase IDH1-mutated Ph-negative MPNs (both untreated and relapsed/refractory) including any of the following:
* polycythemia vera with (PV) ≥ 5% peripheral or bone marrow blasts at time of screening
* essential thrombocythemia (ET) with ≥ 5% peripheral or bone marrow blasts at time of screening
* primary myelofibrosis (PMF) with ≥ 5% peripheral or bone marrow blasts at time of screening
* Atypical CML with ≥ 5% peripheral or bone marrow blasts at time of screening
* MPN-NOS with ≥ 5% peripheral or bone marrow blasts at time of screening
* MDS/MPN Overlap Syndromes including CMML with ≥ 5% peripheral or bone marrow blasts at time of screening
* post-PV myelofibrosis with ≥ 5% blasts peripheral or bone marrow blasts at time of screening
* post-ET myelofibrosis with ≥ 5% blasts peripheral or bone marrow blasts at time of screening
* primary and secondary myelofibrosis with inadequate response to JAK inhibitor regardless of blast percentage. Inadequate response to JAK inhibitor will be defined as lack of achieving any clinical improvement criteria within 12 weeks of of JAK inhibitor initiation.
* Patients can be on cytoreduction at time of study enrollment with hydroxyurea or steroids.
* Age ≥18 years.
* ECOG performance status ≤2
* Patients must have normal organ and marrow function as defined below:
* Creatinine clearance ≥60 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)
* A platelet count of 50 x 109/L should be met for those with chronic-phase myelofibrosis and \< 5% blasts peripherally or in bone marrow
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
* Other eligibility criteria include the following:
* Patients must be at least 4 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.
* The effects of the investigational agents on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
* Ability to understand and the willingness to sign a written informed consent document.

* Patients cannot be on concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in this protocol. Patients cannot have had prior treatment with ivosidenib.
* 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 or they are not currently requiring treatment for an indolent malignancy. Patients with APL and active CNS disease would also be excluded
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to ivosidenib or ruxolitinib.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, venous thromboembolism, stroke, 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 QTc interval ≥ 450 msec or other factors that increase the risk of QT prolongation or arrhythmic events at screening unless due to bundle branch block or pacemaker with approval of the principal investigator.
* Pregnant women are excluded from this study because ruxolitinib and ivosidenib 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 ruxolitinib and ivosidenib, breastfeeding should be discontinued if the mother is treated with any of these agents.
* Patient is known to have dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally.
* Patients receiving any medications or substances that are inhibitors or inducers of CYP3A4 should have eligibility and alternative medications reviewed by site PI.

Contacts and Locations

Study Contact

Clinical Trials Intake

CONTACT

1-855-702-8222

cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator

Anand Patel

PRINCIPAL_INVESTIGATOR

University of Chicago Medicine Comprehensive Cancer Center

Study Locations (Sites)

University of Chicago Medicine Comprehensive Cancer Center

Chicago, Illinois, 60637

United States

Collaborators and Investigators

Sponsor: University of Chicago

Anand Patel, PRINCIPAL_INVESTIGATOR, University of Chicago Medicine Comprehensive Cancer Center

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 Registration Dates

Study Start Date2024-09-19

Study Completion Date2026-05

Study Record Updates

Study Start Date2024-09-19

Study Completion Date2026-05

Terms related to this study

Additional Relevant MeSH Terms

Myeloproliferative Neoplasms