Ivosidenib for Acute Myeloid Leukemia

Recruiting at 1 trial location

Overseen By Amir T Fathi, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must not be taking: Investigational agents

Disqualifiers: Prior transplants, Heart failure, others

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: Unknown

Duration: 24 months

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This clinical trial tests a drug called ivosidenib to determine its effectiveness in helping people with a specific type of acute myeloid leukemia (AML) that has an IDH1 genetic mutation. The researchers aim to find out if ivosidenib can prevent cancer recurrence after a stem cell transplant. Participants will receive either ivosidenib or a placebo (a pill with no active medicine) and take it daily for up to two years. The trial seeks individuals who have undergone a stem cell transplant for IDH1-mutant AML and are ready to begin post-transplant treatment. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, certain medications for graft versus host disease (GVHD) are allowed, and investigational agents not approved for any indication are not permitted unless you leave the study. It's best to discuss your specific medications with the study team.

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

Research has shown that ivosidenib, the treatment being tested, has promising safety results from earlier studies. In one study, researchers administered ivosidenib to patients with acute myeloid leukemia (AML) who had a specific genetic change called the IDH1 mutation. The treatment was generally well-tolerated, meaning most patients did not experience severe side effects.

Specifically, research found that ivosidenib had low toxicity, indicating it did not cause many harmful side effects. This suggests it is relatively safe for people with IDH1-mutated AML. Additionally, long-term studies have shown positive results, such as increased survival rates, when ivosidenib was used with another drug, azacitidine.

These findings provide some confidence in the safety of ivosidenib for treating IDH1-mutated AML. However, individual experiences can vary, so it is important to discuss potential risks and benefits with a healthcare provider before deciding to join a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for AML?

Unlike the standard treatments for acute myeloid leukemia, which typically include chemotherapy and targeted therapies, Ivosidenib offers a novel approach by targeting a specific genetic mutation known as IDH1. This mutation-driven mechanism sets Ivosidenib apart, as it directly interferes with the cancer cell metabolism, potentially leading to more effective outcomes for patients with this mutation. Researchers are excited about Ivosidenib because it not only represents a targeted therapy option but also has the potential to improve remission rates and long-term survival for individuals undergoing hematopoietic stem cell transplantation.

What evidence suggests that ivosidenib might be an effective treatment for acute myeloid leukemia?

Research has shown that ivosidenib can benefit people with acute myeloid leukemia (AML) who have a specific change in their IDH1 gene. In one study, 51% of patients taking ivosidenib with azacitidine achieved complete remission, meaning their cancer symptoms disappeared. Another study found that patients treated with ivosidenib lived longer, with an average survival of 29.3 months compared to 7.9 months for those who did not receive the drug. In this trial, participants will receive either ivosidenib or a placebo after hematopoietic stem cell transplantation (HCT). These findings suggest that ivosidenib can improve survival and remission rates for patients with this specific type of AML. ^{1 2 4 6 7}

Who Is on the Research Team?

Amir Fathi, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with IDH1-mutant acute myeloid leukemia who are undergoing or have undergone a bone marrow transplant. They must be in good health, with specific blood counts and organ functions within normal ranges, and agree to use contraception. Those with recent relapse/refractory disease, other cancers (unless cancer-free for 5 years), previous transplants, hepatitis B/C, heart failure/arrhythmias, or uncontrolled illnesses cannot join.

Inclusion Criteria

Agree to use adequate contraception during the study treatment period and through 90 days after the last dose of treatment

Ability to understand and sign a written informed consent document

I am scheduled for a stem cell transplant from a donor for my cancer.

Exclusion Criteria

I have an active hepatitis B or C infection.

I have severe heart failure, dangerous irregular heartbeats, or poor heart pump function.

I have a history of serious heart rhythm problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Up to 3 months

Treatment

Participants receive ivosidenib or placebo orally once daily in 28-day continuous cycles for up to 24 months

24 months

Regular visits throughout treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Ivosidenib

Trial Overview The study compares ivosidenib—a drug targeting mutant IDH1 enzymes—to a placebo in patients after stem cell transplantation. It's designed to see if ivosidenib can help maintain remission from AML post-transplant by inhibiting the abnormal enzyme produced by mutated genes in these leukemia cells.

How Is the Trial Designed?

Group I: Ivosidenib Experimental Treatment 1 Intervention

After screening and standard of care hematopoietic stem cell transplantation (HCT) and any standard treatment before and after the HSCT, Ivosidenib will be given orally (PO) once daily (QD) in 28-day continuous cycles. Ivosidenib is administered at a pre-determined dose with a goal of 500mg daily. Participants begin study treatment 45 to 90 days after HCT, and treatment will continue for up to 24 months. Study visits and assessments occur throughout study treatment and in follow-up. After the 24-month treatment period, participants are followed for up to 12 additional months.

Group II: Placebo Placebo Group 1 Intervention

After screening and standard of care hematopoietic stem cell transplantation (HCT) and any standard treatment before and after the HSCT, Placebo will be given orally (PO) once daily (QD) in 28-day continuous cycles. Participants begin study treatment (placebo) 45 to 90 days after HCT, and treatment (placebo) will continue for up to 24 months. Study visits and assessments occur throughout study treatment period and in follow-up. After the 24-month treatment period, participants are followed for up to 12 additional months.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Servier

Industry Sponsor

Trials

55

Recruited

45,600+

Published Research Related to This Trial

Ivosidenib has been approved by the FDA for treating patients with IDH1-mutant relapsed/refractory acute myeloid leukemia, highlighting its significance in targeted cancer therapy.

In a phase I trial, 32.8% of patients achieved either a complete remission or a complete remission with partial hematologic recovery, demonstrating the drug's efficacy in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ivosidenib Gets Go-Ahead for AML. [2019]

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 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]

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, 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]

Citations

1. tibsovo.com tibsovo.com/aml/results

AML Clinical Trial Results | TIBSOVO® (ivosidenib tablets) In the clinical study, 51% of people (37 out of 72) on TIBSOVO + azacitidine achieved complete remission (CR) or complete remission with partial hematologic ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40706052/

Long-term results from the AGILE study of azacitidine plus ... Median OS was significantly longer with ivosidenib (29.3 months; 95% CI 13.2, not reached) than with placebo (7.9 months; 95% CI 4.1, 11.3; ...

3. ashpublications.org ashpublications.org/bloodadvances/article/9/20/5177/546354/Long-term-results-from-the-AGILE-study-of

Long-term results from the AGILE study of azacitidine plus ... In long-term follow-up, ivosidenib-azacitidine, with a median OS of 29.3 months, sustained survival and hematologic benefits in mutant IDH1 AML.

4. prnewswire.com prnewswire.com/news-releases/servier-announces-positive-data-from-long-term-follow-up-analysis-of-the-phase-3-agile-trial-of-tibsovo-ivosidenib-in-idh1-mutated-acute-myeloid-leukemia-302513961.html

Servier Announces Positive Data from Long-Term Follow ... Long-term efficacy and safety results published in Blood Advances continue to demonstrate the sustained survival benefit of adding TIBSOVO ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2117344

Ivosidenib and Azacitidine in IDH1-Mutated Acute Myeloid ... Ivosidenib and azacitidine showed significant clinical benefit as compared with placebo and azacitidine in this difficult-to-treat population.

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/6055/526387/Safety-and-Efficacy-of-Ivosidenib-Based-Regimen-in

Safety and Efficacy of Ivosidenib Based Regimen in Patients ... Our data show that ivosidenib-based treatment was successful in four Chinese AML patients with IDH1 mutations, demonstrating that the low toxicity allows for ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.7012

Updated efficacy and safety data from the AGILE study in ... IVO plus azacitidine (AZA) significantly improved event-free survival (EFS), overall survival (OS), complete remission (CR), and CR or CR with partial ...