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

NCT06291987 | Recruiting Phase 1 FDA Drug

• 1 other identifier: IRB23-1681
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Myeloproliferative Neoplasms

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose

  The highest dose of a drug or treatment that does not cause unacceptable side effects.

  At the end of Cycle 1 (each cycle is 28 days)

Secondary Outcomes (5)

• Overall Survival (OS)

  5 years

• Overall Response Rate (ORR)

  5 years

• Time to Response (TTR)

  5 years

• Duration of response (DOR)

  5 years

• Progression free survival (PFS)

  5 years

Study Arms (3)

Dose Level -1

EXPERIMENTAL

Ivosidenib 500mg daily + Ruxolitinib 5mg twice a day

Drug: Ivosidenib; Drug: Ruxolitinib

Dose Level 1

EXPERIMENTAL

Ivosidenib 500mg daily + Ruxolitinib 10mg twice a day

Drug: Ivosidenib; Drug: Ruxolitinib

Dose Level 2

EXPERIMENTAL

Ivosidenib 500mg daily + Ruxolitinib 20mg twice a day

Drug: Ivosidenib; Drug: Ruxolitinib

Interventions

Ivosidenib DRUG

Ivosidenib will be given at assigned dose once daily.

Also known as: TIBSOVO

Dose Level -1; Dose Level 1; Dose Level 2

Ruxolitinib DRUG

Ruxolitinib will be given at assigned dose twice daily.

Also known as: Jakafi

Dose Level -1; Dose Level 1; Dose Level 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

University of Chicago Medicine Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

RECRUITING

MeSH Terms

Conditions

Myeloproliferative Disorders

Interventions

ivosidenib; ruxolitinib

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Anand Patel

  University of Chicago Medicine Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trials Intake

CONTACT

1-855-702-8222; cancerclinicaltrials@bsd.uchicago.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2024
• First Posted: March 4, 2024
• Study Start: September 19, 2024
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: November 5, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)