Ivosidenib for Advanced Solid Cancers, Lymphoma & Histiocytosis

Not currently recruiting at 193 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inducers, CYP3A4 inhibitors

Disqualifiers: Pregnancy, Infection, Organ transplant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 28

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a treatment called ivosidenib (Tibsovo) for certain cancers that didn't respond to other treatments or have returned. It targets cancers with specific genetic changes in the IDH pathway, including solid tumors, lymphomas, and histiocytic disorders. Eligible participants have cancers that persist or return after treatment and possess a specific genetic mutation (IDH1). As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of people.

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

The trial protocol does not specify if you must stop taking your current medications, but you cannot take certain drugs like strong inducers or inhibitors of CYP3A4, and you must avoid investigational drugs and other anti-cancer agents. If you're on medications that prolong the QTc interval, you should discuss alternatives with your doctor.

Is there any evidence suggesting that ivosidenib is likely to be safe for humans?

Studies have shown that ivosidenib has been tested in people with certain types of leukemia and bile duct cancer. Research indicates that common side effects include tiredness, nausea, and some liver issues. Most people can manage these side effects, but those with liver problems require close monitoring.

Ivosidenib is approved for certain conditions, suggesting it is generally safe when used as directed. However, its effectiveness for solid tumors, lymphomas, and histiocytic disorders remains under investigation. Overall, while some side effects are noted, many patients tolerate ivosidenib well. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ivosidenib is unique because it specifically targets the IDH1 mutation, which is not directly addressed by standard treatments for advanced solid cancers, lymphoma, and histiocytosis. Most current therapies focus on broadly attacking cancer cells or boosting the immune response, but ivosidenib works by inhibiting the abnormal enzyme produced by the mutated IDH1 gene, potentially stopping cancer cell growth at its source. Researchers are excited about ivosidenib because this targeted approach could lead to more effective and personalized treatment options with fewer side effects compared to conventional therapies.

What evidence suggests that ivosidenib might be an effective treatment for advanced solid cancers, lymphoma, and histiocytosis?

Studies have shown that ivosidenib, which participants in this trial will receive, can be effective for patients with certain cancers that have an IDH1 mutation. Research indicates that ivosidenib improves outcomes in cancers like cholangiocarcinoma, a type of bile duct cancer. In these cases, patients experienced longer periods without cancer progression. Additionally, ivosidenib is generally safe, making it a promising option for those with IDH1-mutated tumors. Overall, ivosidenib works by stopping cancer cells from growing in tumors with these specific genetic changes. ^{2 3 6 7 8}

Who Is on the Research Team?

Elizabeth D Alva

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for young patients aged between 12 months and 21 years with advanced solid tumors, lymphoma, or histiocytic disorders that have a specific genetic change (IDH1 mutation). They must be able to swallow tablets, have not used IDH1 inhibitors before, and meet certain health criteria like adequate blood counts and organ function. Pregnant individuals or those on certain medications are excluded.

Inclusion Criteria

My white blood cell count is healthy for cancer treatment.

I am between 12 and 21 years old.

I can swallow pills without any issues.

Exclusion Criteria

I am taking medication to prevent graft-versus-host disease after a bone marrow transplant.

I do not have any infections that are currently uncontrolled.

Pregnant or breast-feeding women

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ivosidenib orally once daily. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Up to 2 years

Monthly visits for each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Ivosidenib

Trial Overview The trial is testing Ivosidenib's effectiveness in treating cancers with IDH1 mutations. It's a phase II study focusing on whether this drug can stop cancer cells from growing by targeting the IDH pathway—a critical cell signaling route involved in tumor development.

How Is the Trial Designed?

Group I: Treatment (ivosidenib) Experimental Treatment 1 Intervention

Patients receive ivosidenib PO QD. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Ivosidenib is already approved in United States, European Union for the following indications:

Approved in United States as Tibsovo for:

• Acute myeloid leukemia (AML) with IDH1 mutation

Approved in European Union as Tibsovo for:

• Acute myeloid leukemia (AML) with IDH1 mutation

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Children's Oncology Group

Collaborator

Trials

467

Recruited

241,000+

Published Research Related to This Trial

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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, a targeted oral inhibitor of mutant IDH1, effectively reduces levels of the oncometabolite 2-hydroxyglutarate (2-HG) in patients with advanced hematologic malignancies, particularly at a dose of 500 mg once daily, achieving levels similar to those in healthy individuals.

The drug demonstrated favorable pharmacokinetics, with a long half-life of 72-138 hours and consistent efficacy across various patient demographics, indicating it is safe and effective for treating patients with IDH1 mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pharmacokinetics and pharmacodynamics of ivosidenib in patients with advanced hematologic malignancies with an IDH1 mutation. Fan, B., Dai, D., DiNardo, CD., et al.[2022]

Ivosidenib, an IDH1 inhibitor, significantly improved progression-free survival in patients with IDH1 mutated cholangiocarcinoma, with a median of 2.7 months compared to 1.4 months for placebo (p < 0.0001).

While overall survival showed a trend towards improvement with 10.8 months for ivosidenib versus 9.7 months for placebo (p = 0.06), the results suggest that ivosidenib is a promising treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Utility of Ivosidenib in the Treatment of IDH1-Mutant Cholangiocarcinoma: Evidence To Date. Uson Junior, PLS., Borad, MJ.[2023]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ivosidenib: First Global Approval. Dhillon, S.[2021]

Ivosidenib has shown the ability to induce remission in 30.4% of patients with relapsed or refractory acute myeloid leukemia that have IDH1 mutations, indicating its potential efficacy as a treatment.

The most common serious side effects observed were prolonged QT interval and IDH differentiation syndrome, highlighting the importance of monitoring for these conditions during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ivosidenib Deemed Safe, Effective in AML. [2019]

Citations

1. servier.us servier.us/blog/servier-announces-expansion-of-its-tibsovo-ivosidenib-development-program-investigating-its-safety-and-efficacy-in-patients-living-with-idh1-mutated-cancers-in-both-hematological-malignancies-and-so/

Servier Announces Expansion of its Tibsovo (ivosidenib) ... For MDS patients with an IDH1 mutation, the prognosis has often been associated with worse overall outcomes and in an increased risk of ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8461552/

Final Overall Survival Efficacy Results of Ivosidenib for ... The median survival among patients with advanced disease is approximately less than 12 months, with 5-year survival rates of 10% or less. Most ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7066280/

Clinical pharmacokinetics and pharmacodynamics of ... The data reported here demonstrate that ivosidenib has a favorable PK profile in patients with IDH1-mutated solid tumors, with robust ...

4. pharmasalmanac.com pharmasalmanac.com/articles/servier-expands-tibsovo-ivosidenib-program-to-study-safety-and-efficacy-in-idh1-mutated-hematologic-and-solid-tumor-cancers

Servier Expands Tibsovo (ivosidenib) Program to Study ... Servier today announced updates to two of its Phase 3 programs evaluating TIBSOVO (ivosidenib tablets) in isocitrate dehydrogenase 1 (IDH1)-mutated cancers.

5. tibsovopro.com tibsovopro.com/cca/efficacy

ClarIDHy Trial Efficacy | CCA - TIBSOVO® (ivosidenib tablets) TIBSOVO® DELIVERED IMPROVED OUTCOMES IN CHOLANGIOCARCINOMA (CCA). Study Design; Progression-free Survival; Treatment Duration; Overall Survival; Disease Control ...

6. ema.europa.eu ema.europa.eu/en/documents/product-information/tibsovo-epar-product-information_en.pdf

Tibsovo, INN-ivosidenib - EMA Tibsovo should be used with caution in patients with moderate and severe hepatic impairment and this patient population should be closely monitored (see ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04195555

Study Details | NCT04195555 | Ivosidenib in Treating ... This phase II Pediatric MATCH trial studies how well ivosidenib works in treating patients with solid tumors, including central nervous system tumors, ...

8. withpower.com withpower.com/trial/phase-3-medulloblastoma-5-2020-5fa8f

Ivosidenib for Advanced Solid Cancers, Lymphoma & ... Ivosidenib (Tibsovo) has been studied for safety in people with certain types of leukemia and cholangiocarcinoma. Common side effects include fatigue, nausea, ...