Ivosidenib treatment for patients with unexplained low blood counts and IDH1 mutations

A Pilot Study of Ivosidenib for Patients With Clonal Cytopenia of Undetermined Significance and Mutations in IDH1

This study is testing if a drug called ivosidenib can help people with unexplained low blood counts and specific gene mutations feel better and improve their blood counts.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Washington University School of Medicine (other)
• Locations: 5 sites (Saint Louis, Missouri and 4 other locations)
• Trial ID: NCT05030441 on ClinicalTrials.gov

What this trial studies

This open-label, multicenter study investigates the efficacy of ivosidenib in patients diagnosed with clonal cytopenia of undetermined significance (CCUS) who have confirmed mutations in the IDH1 gene. The study aims to demonstrate that ivosidenib is well-tolerated and can improve blood count abnormalities in these patients. It will be conducted in a decentralized manner, allowing for remote participation. Patients will be monitored for their response to treatment and any potential side effects.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with unexplained cytopenia for at least six months and confirmed IDH1 mutations.

Not a fit: Patients without IDH1 mutations or those with cytopenia due to other identifiable causes may not benefit from this treatment.

Why it matters

Potential benefit: If successful, this treatment could improve blood counts and overall health for patients suffering from CCUS with IDH1 mutations.

How similar studies have performed: While this approach is novel for CCUS, similar studies targeting IDH1 mutations in other hematological conditions have shown promising results.

Eligibility criteria

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.

Where this trial is running

Saint Louis, Missouri and 4 other locations

• Washington University School of Medicine — Saint Louis, Missouri, United States (RECRUITING)
• Northwell Health Cancer Institute (R.J. Zuckerberg Cancer Center) — Lake Success, New York, United States (RECRUITING)
• Memorial Sloan Kettering — New York, New York, United States (WITHDRAWN)
• Cleveland Clinic - Case Comprehensive Cancer Center — Cleveland, Ohio, United States (RECRUITING)
• Ohio State University — Columbus, Ohio, United States (WITHDRAWN)

Study contacts

• Principal investigator: Kelly Bolton, M.D., Ph.D. — Washington University School of Medicine
• Study coordinator: Kelly Bolton, M.D., Ph.D.

Conditions: Clonal Cytopenia of Undetermined Significance