291 Participants Needed

AG-120 for Blood Cancers

Recruiting at 32 trial locations
Id
Overseen ByInstitut de Recherches Internationales Servier Clinical Studies Department
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: Institut de Recherches Internationales Servier
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Approved in 1 JurisdictionThis treatment is already approved in other countries

Trial Summary

Do I have to stop taking my current medications for the AG-120 trial?

The trial protocol does not specify if you need to stop taking your current medications, but it does exclude patients taking medications that prolong the QT interval (a measure of heart rhythm). It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug AG-120 (Ivosidenib) for blood cancers?

Ivosidenib has been shown to be effective in treating acute myeloid leukemia (AML) with IDH1 mutations, achieving complete remission in about 33% of patients with relapsed or refractory AML. It also improved survival rates when combined with azacitidine in newly diagnosed AML patients with IDH1 mutations.12345

Is ivosidenib (AG-120, Tibsovo) safe for humans?

Ivosidenib has been studied in patients with certain blood cancers and is generally considered safe, but it can cause serious side effects like differentiation syndrome (a condition where cancer cells rapidly change), high white blood cell counts, and heart rhythm changes. Common side effects include tiredness, nausea, diarrhea, and rash. Long-term safety is still being evaluated.12345

How is the drug ivosidenib unique for treating blood cancers?

Ivosidenib is unique because it specifically targets and inhibits the mutant IDH1 protein, which is responsible for producing a harmful substance called 2-hydroxyglutarate (2-HG) that contributes to cancer growth. This drug is taken orally and is particularly effective for patients with blood cancers that have an IDH1 mutation, offering a targeted approach compared to traditional chemotherapy.12346

What is the purpose of this trial?

The purpose of this Phase I, multicenter study is to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of AG-120 in advanced hematologic malignancies that harbor an IDH1 mutation. The first portion of the study is a dose escalation phase where cohorts of patients will receive ascending oral doses of AG-120 to determine maximum tolerated dose (MTD) and/or the recommended Phase II dose. The second portion of the study is a dose expansion phase where four cohorts of patients will receive AG-120 to further evaluate the safety, tolerability, and clinical activity of the recommended Phase II dose. Additionally, the study includes a substudy evaluating the safety and tolerability, clinical activity, pharmacokinetics, and pharmacodynamics of AG-120 in subjects with relapsed or refractory myelodysplastic syndrome with an IDH1 mutation. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Eligibility Criteria

Adults (18+) with advanced blood cancers like AML or MDS that have a specific IDH1 mutation can join. They must be able to undergo regular bone marrow, blood, and urine tests, not be pregnant, and have an ECOG performance status of 0-2. Adequate liver and kidney function is required. Those with severe heart problems, recent cancer treatments within 14 days (except hydroxyurea), active infections including HIV or hepatitis B/C, CNS leukemia symptoms or history of it without clinical suspicion are excluded.

Inclusion Criteria

My platelet count is at least 20,000/µL, transfusions included.
My blood cancer has a specific IDH1 R132 gene mutation.
I am willing to undergo repeated bone marrow biopsies, blood, and urine tests.
See 5 more

Exclusion Criteria

I haven't had cancer treatment or radiotherapy in the last 14 days, except for hydroxyurea.
I do not have a severe infection or unexplained fever over 38.5°C.
I have severe heart failure or my heart's pumping ability is less than 40%.
See 12 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Cohorts of patients receive ascending oral doses of AG-120 to determine maximum tolerated dose (MTD) and/or the recommended Phase II dose

Up to 26 weeks
Continuous dosing in 28-day cycles

Dose Expansion

Four cohorts of patients receive AG-120 to further evaluate the safety, tolerability, and clinical activity of the recommended Phase II dose

Up to 26 weeks
Continuous dosing in 28-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • AG-120
Trial Overview AG-120 is being tested in patients with certain mutations in their blood cancer cells. The trial has two parts: first finding the highest dose people can take without too many side effects (dose escalation) and then giving more people this dose to see how well it works and if it's safe (dose expansion). There's also a special part for those whose myelodysplastic syndrome came back after treatment.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: AG-120Experimental Treatment1 Intervention
AG-120 administered continuously as a single agent dosed orally every day of a 28-day cycle.

AG-120 is already approved in United States for the following indications:

🇺🇸
Approved in United States as Tibsovo for:
  • Acute myeloid leukemia (AML) with a susceptible IDH1 mutation

Find a Clinic Near You

Who Is Running the Clinical Trial?

Institut de Recherches Internationales Servier

Lead Sponsor

Trials
91
Recruited
67,100+

Findings from Research

Ivosidenib (Tibsovo®) is an oral medication that specifically inhibits mutated IDH1 enzymes, which are linked to the production of 2-hydroxyglutarate (2-HG), a metabolite that contributes to the development of certain cancers like acute myeloid leukaemia (AML).
The drug has received approval in the USA for treating patients with relapsed or refractory AML who have a specific IDH1 mutation, and ongoing clinical trials are exploring its efficacy in other cancers such as cholangiocarcinoma and glioma.
Ivosidenib: First Global Approval.Dhillon, S.[2021]
Ivosidenib is an FDA-approved treatment for adults with relapsed or refractory acute myeloid leukemia (R/R AML) with an IDH1 mutation, showing a complete remission (CR) + partial hematologic recovery (CRh) rate of 33% in a study of 174 patients over an 8.3-month follow-up.
While ivosidenib demonstrated short-term efficacy, including a median duration of response of 8.2 months and a 37% conversion rate from transfusion dependence to independence, serious adverse reactions such as differentiation syndrome and QT interval prolongation were noted, highlighting the need for ongoing safety assessments.
FDA Approval Summary: Ivosidenib for Relapsed or Refractory Acute Myeloid Leukemia with an Isocitrate Dehydrogenase-1 Mutation.Norsworthy, KJ., Luo, L., Hsu, V., et al.[2020]
Ivosidenib, when combined with azacitidine, significantly improves event-free survival and overall survival in older adults or those with comorbidities suffering from IDH1-mutated acute myeloid leukemia, as shown in a phase 3 study with improved survival rates (HR 0.35 and HR 0.44).
The combination therapy also resulted in a higher complete remission rate (47% vs. 15% with placebo) and maintained a safety profile similar to ivosidenib alone, with notable adverse effects including differentiation syndrome and QT interval prolongation.
FDA Approval Summary: Ivosidenib in Combination with Azacitidine for Treatment of Patients with Newly Diagnosed Acute Myeloid Leukemia with an IDH1 Mutation.Woods, A., Norsworthy, KJ., Wang, X., et al.[2023]

References

Ivosidenib: First Global Approval. [2021]
FDA Approval Summary: Ivosidenib for Relapsed or Refractory Acute Myeloid Leukemia with an Isocitrate Dehydrogenase-1 Mutation. [2020]
FDA Approval Summary: Ivosidenib in Combination with Azacitidine for Treatment of Patients with Newly Diagnosed Acute Myeloid Leukemia with an IDH1 Mutation. [2023]
Clinical pharmacokinetics and pharmacodynamics of ivosidenib in patients with advanced hematologic malignancies with an IDH1 mutation. [2022]
Ivosidenib Deemed Safe, Effective in AML. [2019]
Ivosidenib induces deep durable remissions in patients with newly diagnosed IDH1-mutant acute myeloid leukemia. [2023]
Unbiased ResultsWe believe in providing patients with all the options.
Your Data Stays Your DataWe only share your information with the clinical trials you're trying to access.
Verified Trials OnlyAll of our trials are run by licensed doctors, researchers, and healthcare companies.
Back to top
Terms of Service·Privacy Policy·Cookies·Security