Clinical trial NCT05030441: Ivosidenib for Patients With Clonal Cytopenia of Undetermined Significance and Mutations in IDH1
Official title: A Pilot Study of Ivosidenib for Patients With Clonal Cytopenia of Undetermined Significance and Mutations in IDH1
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Clonal Cytopenia of Undetermined Significance
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Servier Hellas Pharmaceuticals Ltd.
name: Gateway for Cancer Research
First posted: 2021-09-01
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


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.

Primary outcomes:
measure: Rate of improvement in hematologic parameters
timeFrame: Through 30 days after completion of treatment (estimated to be 61 months)
Secondary outcomes:
measure: Change in mutant IDH1 variant allele fraction
timeFrame: Through completion of treatment (estimated to be 60 months)
measure: Disease free survival
timeFrame: Through 30 days after completion of treatment (estimated to be 61 months)
measure: Number of adverse events as measured by CTCAE v 5.0
timeFrame: Through 30 days after completion of treatment (estimated to be 61 months)
measure: Duration of hematologic response
timeFrame: Through completion of treatment (estimated to be 60 months)
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Lake Success
country: United States
facility: Northwell Health Cancer Institute (R.J. Zuckerberg Cancer Center)
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic - Case Comprehensive Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
Study officials:
affiliation: Washington University School of Medicine
name: Kelly Bolton, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: