Olutasidenib for Leukemia

Recruiting at 1 trial location

Overseen By Amandeep Salhotra, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must be taking: IDH1 inhibitors

Disqualifiers: Active GVHD, Uncontrolled infection, Active malignancy, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 30

Duration: 24 months

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called olutasidenib to determine if it can safely prevent leukemia from returning in individuals who have undergone a bone marrow transplant. It targets patients with specific blood cancers (AML, MDS, or CMML) who have an IDH1 mutation. Participants must have already had a transplant and be in remission, meaning their cancer is not currently active. Olutasidenib aims to slow or stop cancer cell growth, and the trial will assess its effectiveness and tolerability. This trial may suit those who have had a transplant for one of these cancers with the IDH1 mutation and are currently in remission. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering a chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor to get a clear answer based on your specific situation.

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

Research has shown that olutasidenib is generally well-tolerated by patients. In some studies, patients with relapsed or hard-to-treat acute myeloid leukemia (AML) who took olutasidenib experienced long-lasting improvements in their symptoms. Most of these patients did not need blood transfusions during this time, which is a positive indicator.

Olutasidenib has been tested in older patients with AML and was generally well-tolerated. While some side effects might occur, they are usually manageable. It is important to note that this trial is in an early stage, so researchers are still gathering detailed safety information. However, current data suggest that olutasidenib could be a promising and manageable treatment option for those considering it. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Olutasidenib is unique because it targets specific mutations in leukemia cells, offering a more tailored approach compared to standard chemotherapy treatments. Most treatments for leukemia involve broad-spectrum chemotherapy that can affect both healthy and cancerous cells, leading to significant side effects. Olutasidenib, however, specifically inhibits mutated forms of the IDH1 enzyme found in some leukemia patients, potentially reducing side effects and improving effectiveness. Researchers are excited about this treatment because it represents a shift toward more personalized medicine, which could lead to better outcomes for patients with fewer adverse effects.

What evidence suggests that olutasidenib might be an effective treatment for preventing relapse in leukemia?

Research shows that olutasidenib, an IDH1 inhibitor, may help treat certain blood cancers, such as acute myeloid leukemia (AML), with specific genetic changes known as IDH1 mutations. In earlier studies, olutasidenib led to lasting complete remissions in patients whose AML returned or did not respond to previous treatments. Specifically, out of 16 patients, 7 experienced significant improvement or disappearance of their cancer symptoms. The medication also helped some patients become independent of regular blood transfusions. This trial will administer olutasidenib to participants to evaluate its effectiveness in preventing cancer recurrence after a transplant in patients with AML, myelodysplastic syndrome (MDS), or chronic myelomonocytic leukemia (CMML) who have an IDH1 mutation. ^{1 3 4 6 7}

Who Is on the Research Team?

Amandeep Salhotra

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with IDH1 mutated AML, MDS, or CMML who have had a donor hematopoietic cell transplant. It's designed to see if the drug olutasidenib can prevent their disease from coming back.

Inclusion Criteria

Documented informed consent of the participant and/or legally authorized representative

I am mostly able to care for myself and remain up and about.

Specific blood count requirements: ANC > 1000/mm^3, Hemoglobin ≥ 8.0 gm/dL, Platelets ≥ 50,000/mm^3

Exclusion Criteria

Prospective participants unable to comply with all study procedures

I am not pregnant or breastfeeding.

History of allergic reactions to compounds of similar composition to study agent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive olutasidenib orally twice daily on days 1-28 of each cycle, starting 50-120 days after transplant. Cycles repeat every 28 days for up to 24 cycles.

24 months

Monthly visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and then up to 2 years.

2 years

Follow-up visits at 30 days and periodically up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Olutasidenib

Trial Overview The trial is testing the safety and effectiveness of olutasidenib, an IDH1 inhibitor that aims to slow down or stop cancer cells from growing. This phase I trial will determine if it's safe and tolerable for preventing relapse after transplant.

How Is the Trial Designed?

Group I: Treatment (olutasidenib) Experimental Treatment 2 Interventions

Starting 50-120 days after transplant, patients receive olutasidenib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection on study.

Olutasidenib is already approved in United States for the following indications:

Approved in United States as Rezlidhia for:

• Acute Myeloid Leukemia (AML) with a susceptible IDH1 mutation

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Olutasidenib (REZLIDHIATM) is an IDH1 inhibitor that has been approved in the USA for treating adults with relapsed or refractory acute myeloid leukaemia (AML) who have a specific IDH1 mutation.

The approval of olutasidenib marks a significant milestone in targeted cancer therapy, as it provides a new treatment option for patients with R/R AML based on genetic testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olutasidenib: First Approval. Kang, C.[2023]

Glasdegib, a small-molecule inhibitor targeting the hedgehog pathway, was approved by the FDA for treating newly diagnosed acute myeloid leukemia (AML) in patients over 75 or those unable to undergo intensive chemotherapy, showing significant promise in improving patient outcomes.

In a phase II trial, the combination of glasdegib with low-dose cytarabine (LDAC) nearly doubled the median overall survival of patients compared to LDAC alone, highlighting its efficacy in a vulnerable patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glasdegib for the treatment of adult patients with newly diagnosed acute myeloid leukemia or high-grade myelodysplastic syndrome who are elderly or otherwise unfit for standard induction chemotherapy. Goldsmith, SR., Lovell, AR., Schroeder, MA.[2019]

In a phase Ib/II trial involving 26 patients with relapsed/refractory gliomas carrying the IDH1R132X mutation, olutasidenib (150 mg twice daily) was well tolerated with no dose-limiting toxicities observed, indicating a favorable safety profile.

The treatment showed preliminary clinical activity, with a disease control rate of 48%, including 8% of patients achieving a partial response and 32% maintaining stable disease for at least 4 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olutasidenib (FT-2102) in patients with relapsed or refractory IDH1-mutant glioma: A multicenter, open-label, phase Ib/II trial. de la Fuente, MI., Colman, H., Rosenthal, M., et al.[2023]

Olutasidenib, a selective inhibitor of mutant IDH1, was well tolerated in patients with acute myeloid leukaemia or myelodysplastic syndrome, with no dose-limiting toxicities reported during the study, and a recommended phase 2 dose of 150 mg twice daily established based on safety and efficacy.

The study showed promising clinical activity, with 41% of patients with relapsed or refractory acute myeloid leukaemia responding to olutasidenib monotherapy, and an even higher response rate of 77% in treatment-naive patients receiving olutasidenib in combination with azacitidine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olutasidenib alone or with azacitidine in IDH1-mutated acute myeloid leukaemia and myelodysplastic syndrome: phase 1 results of a phase 1/2 trial. Watts, JM., Baer, MR., Yang, J., et al.[2022]

In a study involving 153 patients with relapsed/refractory acute myeloid leukemia (AML) who had the mIDH1 mutation, olutasidenib showed a 35% rate of complete remission and an overall response rate of 48%, indicating its efficacy as a treatment option.

Olutasidenib was associated with manageable side effects, with significant adverse events including febrile neutropenia and anemia occurring in 20% of patients, while also achieving transfusion independence in 34% of transfusion-dependent patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olutasidenib (FT-2102) induces durable complete remissions in patients with relapsed or refractory IDH1-mutated AML. de Botton, S., Fenaux, P., Yee, K., et al.[2023]

Olutasidenib, an oral IDH1mut inhibitor, received regular approval for treating relapsed/refractory IDH1mut acute myeloid leukemia (AML) on December 1, 2022, following its rapid development since 2016.

In clinical trials, olutasidenib showed high rates of durable remission and significant benefits like transfusion independence in patients with R/R IDH1mut AML, highlighting its efficacy as a targeted therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olutasidenib: from bench to bedside. Venugopal, S., Watts, J.[2023]

In a study of 124 patients with relapsed or refractory acute myeloid leukemia (AML) with an IDH2 mutation, enasidenib treatment resulted in a higher overall response rate (77%) compared to other first-line therapies (52%).

Patients treated with enasidenib had better progression-free survival (8 months) and overall survival (11 months) compared to those receiving other therapies (5 months and 6 months, respectively), and they experienced significantly fewer hospitalizations (14% vs. 46%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world clinical outcomes with enasidenib in relapsed or refractory acute myeloid leukemia. Klink, AJ., Gajra, A., Knoth, RL., et al.[2022]

Raltitrexed, administered weekly for 3 weeks to children with refractory leukemia, was well tolerated, with the maximum tolerated dose identified as 2.1 mg/m², and reversible liver toxicity observed at higher doses.

The treatment showed preliminary antileukemic activity, with three objective responses noted, suggesting that further evaluation of raltitrexed in this patient population is warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial and pharmacokinetic study of raltitrexed in children with recurrent or refractory leukemia: a pediatric oncology group study. Horton, TM., Blaney, SM., Langevin, AM., et al.[2014]

In a study involving 20 patients with myelodysplastic syndrome (MDS), the farnesyltransferase inhibitor R115777 showed a 30% overall response rate, similar to results seen in acute leukemia, indicating its potential efficacy in treating hematologic malignancies.

BMS-214662, administered as a weekly intravenous infusion, resulted in over a 50% decrease in bone marrow blasts in 23% of patients with acute leukemia or MDS, with 18% achieving normalization of blast counts, suggesting significant therapeutic activity even in patients without ras mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical development of farnesyltransferase inhibitors in leukemias and myelodysplastic syndrome. Kurzrock, R., Cortes, J., Kantarjian, H.[2007]

A study analyzing gene expression in 58 bone marrow samples from AML patients identified eight markers that can predict response to the drug tipifarnib, with the AKAP13 gene being the most significant.

AKAP13 overexpression was linked to resistance against tipifarnib, indicating that measuring this gene could help identify which patients are less likely to benefit from the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of molecular predictors of response in a study of tipifarnib treatment in relapsed and refractory acute myelogenous leukemia. Raponi, M., Harousseau, JL., Lancet, JE., et al.[2016]

Recent research has identified new molecular therapeutic targets for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), leading to the development of promising new drug classes such as farnesyltransferase inhibitors and receptor tyrosine kinase inhibitors.

Early clinical trials suggest these new drugs may change the standard treatment for MDS, focusing on resolving blood cell deficiencies and targeting the disease's specific mechanisms, although most studies are still in the early stages of development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibitors of signaling in myelodysplastic syndrome. Gore, SD.[2009]

Targeted therapies like all-trans retinoic acid (ATRA) combined with chemotherapy have significantly improved disease-free survival in patients with acute promyelocytic leukemia (APL).

Imatinib mesylate has shown remarkable effectiveness in treating chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL), highlighting the importance of targeting specific molecular pathways in leukemia treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advancing the treatment of hematologic malignancies through the development of targeted interventions. Tallman, MS.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10362540/

Olutasidenib (FT-2102) induces durable complete remissions ... Olutasidenib induced durable remissions in patients with mIDH1 R/R AML; transfusion independence was achieved across all response groups.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6545

A phase 2 study of olutasidenib in relapsed/refractory acute ... Conclusions: Higher response rates (including CR and CRh) and greater survival were observed in patients receiving OLU following 1-2 versus ≥3 ...

3. rigel.com rigel.com/news-media/press-releases/detail/383/rigel-announces-publication-of-data-on-rezlidhia

Rigel Announces Publication of Data on REZLIDHIA® ... Of the 16 R/R patients, 7 (43.8%) achieved a composite complete remission (CRc), 4 (25%) achieved complete remission (CR), and 1 (6.3%) achieved ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124107136

Treatment Patterns and Outcomes of Olutasidenib in ... The study included 47 patients diagnosed with AML. Median age at diagnosis was 71 years, and 55% were female. 75% patients started olutasidenib ...

5. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1525/531606/Effectiveness-of-Olutasidenib-Versus-Ivosidenib-in

Effectiveness of Olutasidenib Versus Ivosidenib in Patients ... Effectiveness outcomes included composite complete remission (CRc) as best response (comprising complete remission [CR], CR with partial ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.6527

Safety and efficacy of olutasidenib treatment in elderly ... Conclusions: Olutasidenib was generally well tolerated in elderly patients with R/R mIDH1AML and induced durable remissions. Despite the ...

7. jhoonline.biomedcentral.com jhoonline.biomedcentral.com/articles/10.1186/s13045-024-01657-z

Olutasidenib in combination with azacitidine induces durable ... Olutasidenib plus azacitidine induced high response rates and durable remissions with a tolerable side effect profile in patients with R/R AML with diverse ...