What side effects are associated with this type of intervention?

Ivosidenib, an IDH1 inhibitor, is being studied for its efficacy in treating Clonal Cytopenia of Undetermined Significance (CCUS). Common side effects associated with IDH1 inhibitors like Ivosidenib include fatigue, nausea, diarrhea, leukocytosis, and QT prolongation. Additionally, patients may experience elevated liver enzymes and differentiation syndrome, which is characterized by fever, dyspnea, and rapid weight gain. These side effects are generally manageable with supportive care and dose adjustments.

What prior FDA approvals exist?

Ivosidenib is an IDH1 inhibitor used in the treatment of acute myeloid leukemia (AML) with a specific IDH1 mutation. Another related drug is Enasidenib, an IDH2 inhibitor, which has also been approved for the treatment of relapsed or refractory AML with an IDH2 mutation. These drugs target specific genetic mutations within the cancer cells, aiming to inhibit the abnormal enzyme activity that contributes to the disease. While these approvals are primarily for AML, they represent a class of targeted therapies that could be relevant for conditions like Clonal Cytopenia with similar genetic mutations.

What other types of research exist?

Promising novel alternatives to Ivosidenib for Clonal Cytopenia patients in 2024 may include other targeted therapies such as Vorinostat, which has shown efficacy in combination with other agents in hematologic malignancies. Additionally, newer PI3K inhibitors like Duvelisib, which have demonstrated activity in various hematologic conditions, could be considered. These alternatives should be discussed with a healthcare provider to determine the best personalized treatment plan.

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IDH1 Inhibitor

Ivosidenib for Blood Disorders

Phase 2

Recruiting

Led By Kelly Bolton, M.D.

Research Sponsored by Washington University School of Medicine

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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.

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

Must not have

Active malignancy (defined as > 1 cm disease on most recent CT scan in the past 6 months)

Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia

Timeline

Screening 3 weeks

Treatment Varies

Follow Up through completion of treatment (estimated to be 60 months)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a medication called ivosidenib in patients with a specific blood condition and a genetic mutation. The goal is to see if the medication can safely improve their blood counts. The study is also designed to be conducted remotely. Ivosidenib has shown significant improvements in patients with certain types of cancers.

Who is the study for?

Adults with clonal cytopenia of undetermined significance (CCUS) and specific IDH1 gene mutations who have had unexplained low blood counts for at least six months. Participants must be in stable health, not pregnant or breastfeeding, without active cancer or heart issues, and able to consent.

What is being tested?

The trial is testing Ivosidenib's safety and effectiveness in improving blood count abnormalities in patients with CCUS carrying IDH1 mutations. It's an open-label study where all participants receive the drug, conducted remotely across multiple centers.

What are the potential side effects?

Potential side effects of Ivosidenib may include but are not limited to digestive disturbances, liver enzyme elevations, fatigue, joint pain or swelling, skin problems like rash or itchiness, and changes in heart rhythm.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer has a specific IDH1 gene mutation.

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I have had low blood counts for over 6 months without a known cause.

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My cancer has a specific IDH1 gene mutation.

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I am 18 years old or older.

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I can take care of myself and perform daily activities.

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My liver and kidney functions are within the required limits.

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I am 18 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My most recent scan shows cancer larger than 1 cm.

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I do not have any uncontrolled illnesses like infections or heart problems.

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I have a history of PML.

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My heart's QT interval is normal and I don't have risk factors for heart rhythm problems.

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I am currently undergoing treatment for a solid tumor cancer.

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I am on medication that strongly affects liver enzyme levels.

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I have a condition that affects my ability to swallow or absorb pills.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ through completion of treatment (estimated to be 60 months)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~through completion of treatment (estimated to be 60 months)

This trial's timeline: 3 weeks for screening, Varies for treatment, and through completion of treatment (estimated to be 60 months) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Rate of improvement in hematologic parameters

Secondary study objectives

Change in mutant IDH1 variant allele fraction

Disease free survival

Side effects data

From 2021 Phase 3 trial • 187 Patients • NCT02989857

28%

Nausea

28%

Diarrhoea

23%

Fatigue

21%

Oedema peripheral

16%

Abdominal pain

16%

Anaemia

14%

Decreased appetite

14%

Weight decreased

12%

Vomiting

12%

Asthenia

12%

Cough

12%

Ascites

12%

Constipation

12%

Arthralgia

Hypertension

Abdominal pain upper

Dizziness

Muscle spasms

Muscular weakness

Dyspnoea

Blood alkaline phosphatase increased

Upper respiratory tract infection

Hypoalbuminaemia

Pruritus

Hypophosphataemia

Aspartate aminotransferase increased

Alanine aminotransferase increased

Insomnia

Abdominal discomfort

Rash

Hypokalaemia

Back pain

White blood cell count decreased

Hyperglycaemia

Hyperkalaemia

Pyrexia

Headache

Abdominal distension

Blood bilirubin increased

Confusional state

Platelet count decreased

Chills

Electrocardiogram QT prolonged

Cholangitis

Gastrointestinal haemorrhage

Intestinal pseudo-obstruction

Biliary obstruction

Bacteraemia

Clostridium difficile colitis

Escherichia bacteraemia

Hip fracture

Hypercalcaemia

Encephalopathy

Acute kidney injury

Hypotension

Gastrooesophageal reflux disease

Hypomagnesaemia

Blood creatinine increased

Dyspepsia

Urinary tract infection

Rash maculo-papular

Dry mouth

Multiple sclerosis relapse

Spinal cord compression

Syncope

Hyponatraemia

Hepatic cirrhosis

Oesophageal varices haemorrhage

Upper gastrointestinal haemorrhage

100%

80%

60%

40%

20%

Study treatment Arm

After Cross Over to AG-120

AG-120

Placebo

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: IvosidenibExperimental Treatment1 Intervention

-Ivosidenib is an oral drug which will be administered on an outpatient basis at a dose of 500 mg daily for up to 5 years. Each cycle is 28 days.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ivosidenib

2019

Completed Phase 1

~20

0 / 14Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Ivosidenib, an IDH1 inhibitor, works by targeting and inhibiting the mutated IDH1 enzyme, which is involved in the abnormal production of 2-hydroxyglutarate (2-HG). This metabolite disrupts normal cellular differentiation and contributes to the clonal expansion of abnormal blood cells. By inhibiting IDH1, Ivosidenib reduces 2-HG levels, thereby promoting the differentiation of immature blood cells into mature, functional cells. This mechanism is crucial for Clonal Cytopenia patients as it addresses the underlying cause of their cytopenias, potentially improving blood counts and reducing the risk of progression to more severe hematologic conditions.

Cluster-Like Headache Revealing Polycythemia Vera: A Case Report.Optimal use of thrombopoietin receptor agonists in immune thrombocytopenia.