- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05030441
Ivosidenib for Patients With Clonal Cytopenia of Undetermined Significance and Mutations in IDH1
A Pilot Study of Ivosidenib for Patients With Clonal Cytopenia of Undetermined Significance and Mutations in IDH1
This is an open-label, multicenter study exploring the efficacy of ivosidenib in patients with clonal cytopenia of undetermined significance (CCUS) with mutations in IDH1. The purpose is to establish proof of principle that ivosidenib is well-tolerated and potentially efficacious in improving blood count abnormalities in these patients.
The study will also be offered in a decentralized, remote structure to patients.
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Kelly Bolton, M.D., Ph.D.
- Phone Number: 314-273-5711
- Email: bolton@wustl.edu
Study Locations
-
-
Missouri
-
Saint Louis, Missouri, United States, 63110
- Recruiting
- Washington University School of Medicine
-
Contact:
- Kelly Bolton, M.D., Ph.D.
- Phone Number: 314-273-5711
- Email: bolton@wustl.edu
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Principal Investigator:
- Kelly Bolton, M.D., Ph.D.
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New York
-
Lake Success, New York, United States, 11042
- Not yet recruiting
- Northwell Health Cancer Institute
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Contact:
- Bradley Goldberg, M.D.
- Phone Number: 516-734-7606
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Principal Investigator:
- Bradley Goldberg, M.D.
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New York, New York, United States, 10065
- Not yet recruiting
- Memorial Sloan Kettering
-
Contact:
- Eytan Stein, M.D.
- Phone Number: 646-608-3749
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Principal Investigator:
- Eytan Stein, M.D.
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-
Ohio
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Cleveland, Ohio, United States, 44195
- Not yet recruiting
- Cleveland Clinic - Case Comprehensive Cancer Center
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Contact:
- Bhumika Patel, M.D.
- Phone Number: 216-444-8655
- Email: patelb3@ccf.org
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Principal Investigator:
- Bhumika Patel, M.D.
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Columbus, Ohio, United States, 43210
- Withdrawn
- Ohio State University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
Unexplained cytopenia for at least 6 months. Cytopenia is defined as the presence of ≥1 blood count indexes below the following thresholds:
- Hgb <10 g/dL
- ANC <1.8 × 10^9/L
- Platelets <100 × 10^9/L
- IDH1 gene mutation (R132) confirmed by droplet digital PCR (ddPCR) testing, at a frequency > 2%. This will be performed locally and confirmed at Washington University.
- At least 18 years of age.
- ECOG performance status 0-2
Adequate organ function as defined below:
- AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
- Serum total bilirubin < 1.5 x IULN (an upper limit of bilirubin 5mg/dL is acceptable if it can be attributed to Gilbert's syndrome or erythropoiesis)
- Serum creatinine < 2 x IULN or creatinine clearance > 50 mL/min by Cockcroft-Gault glomerular filtration rate estimation
- The effects of ivosidenib on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (defined in Section 5.5) prior to study entry, for the duration of study participation, and for 90 days after the last dose of ivosidenib. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study, and for 90 days after the last dose of ivosidenib.
- Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Exclusion Criteria:
Indication of hematologic disease by bone marrow biopsy within 6 months of study entry.
*Evidence of disease progression from time of bone marrow biopsy to enrollment based on investigator review of symptoms and complete blood counts
- Active malignancy (defined as > 1 cm disease on most recent CT scan in the past 6 months).
- Currently receiving therapy for solid tumor malignancy.
- Currently receiving any other investigational agents.
- Known dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally.
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to ivosidenib or other agents used in the study.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 72 hours of study entry.
- Heartrate corrected QT interval (QTc) > 450 msec or with other factors that increase the risk of QT prolongation or arrhythmic events (e.g. heart failure, hypokalemia, family history of long QT interval syndrome).
- Known medical history of progressive multifocal leukoencephalopathy (PML).
- Currently taking medications known to be CYP3A4 strong inducers and sensitive substrates.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Ivosidenib
-Ivosidenib is an oral drug which will be administered on an outpatient basis at a dose of 500 mg daily for up to 17 months (approximately 18 28-day cycles), with each cycle being 28 days.
|
. Patients should take ivosidenib at approximately the same time every day, with or without food, but should be instructed to avoid a high-fat meal as well as grapefruit and grapefruit products.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of improvement in hematologic parameters
Time Frame: Through 30 days after completion of treatment (estimated to be 18 months)
|
Will be evaluated according to a modified version of the IWG 2006 Criteria for Hematologic Improvement for patients with MDS on clinical trials
|
Through 30 days after completion of treatment (estimated to be 18 months)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in mutant IDH1 variant allele fraction
Time Frame: Through completion of treatment (estimated to be 17 months)
|
-ddPCR is a highly sensitive and accurate method for quantifying VAF.
This will be performed centrally at the Washington University clinical pathology laboratory using standard procedures.
To account for assay variation, the investigators will perform 10 runs using the ddPCR assay and take the mean VAF as the final measurement.
|
Through completion of treatment (estimated to be 17 months)
|
Disease free survival
Time Frame: Through 30 days after completion of treatment (estimated to be 18 months)
|
-Events include development of MDS/AML or death.
|
Through 30 days after completion of treatment (estimated to be 18 months)
|
Number of adverse events as measured by CTCAE v 5.0
Time Frame: Through 30 days after completion of treatment (estimated to be 18 months)
|
Through 30 days after completion of treatment (estimated to be 18 months)
|
Collaborators and Investigators
Investigators
- Principal Investigator: Kelly Bolton, M.D., Ph.D., Washington University School of Medicine
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 202110038
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ANALYTIC_CODE
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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