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

Trial Summary

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.

What data supports the effectiveness of the drug Ivosidenib for treating Acute Myeloid Leukemia?

Ivosidenib, when combined with azacitidine, has been shown to improve survival rates and increase the rate of complete remission in patients with newly diagnosed IDH1-mutated acute myeloid leukemia, especially in older adults or those with other health issues. In a study, 47% of patients achieved complete remission compared to 15% with a placebo. ^{1 2 3 4 5}

Is ivosidenib safe for humans?

Ivosidenib has been studied for safety in people with acute myeloid leukemia (AML) and is generally considered safe, but it can cause some serious side effects. Common side effects include fatigue, nausea, and diarrhea, while serious ones can include differentiation syndrome (a condition where leukemia cells change and cause inflammation), high white blood cell counts, and heart rhythm changes. Long-term safety is still being studied. ^{1 3 4 6 7}

How does the drug ivosidenib differ from other treatments for acute myeloid leukemia?

Ivosidenib is unique because it specifically targets and inhibits the mutated IDH1 enzyme, which is involved in the progression of acute myeloid leukemia. This drug is particularly used for patients with relapsed or refractory AML who have an IDH1 mutation, offering a targeted approach compared to traditional chemotherapy. ^{1 3 4 5 6}

What is the purpose of this trial?

This is a Phase 2 study of the study drug, ivosidenib (a mutant IDH1 inhibitor), compared to placebo, given to patients with IDH1-mutant acute myeloid leukemia (AML) after hematopoietic stem cell transplantation (HCT).

Research Team

Amir Fathi, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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.

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]

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 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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Ivosidenib: First Global Approval. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Ivosidenib and Azacitidine in IDH1-Mutated Acute Myeloid Leukemia. [2022]

3. United States 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. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Ivosidenib Deemed Safe, Effective in AML. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Ivosidenib Gets Go-Ahead for AML. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Ivosidenib for Relapsed or Refractory Acute Myeloid Leukemia with an Isocitrate Dehydrogenase-1 Mutation. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Ivosidenib: IDH1 Inhibitor for the Treatment of Acute Myeloid Leukemia. [2023]