Olutasidenib for Myeloid Leukemia

Overseen By Jeremy Ramdial, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anti-leukemic agents

Disqualifiers: Active HIV, Hepatitis B, Hepatitis C, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 year

31 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assess the safety and tolerability of the drug olutasidenib for individuals with certain blood cancers, such as myeloid leukemia, following a stem cell transplant. The trial will evaluate whether regular administration of olutasidenib can help maintain recovery. This trial may suit individuals who have undergone a stem cell transplant for myeloid leukemia and have an IDH1 mutation (a specific genetic change) in their cancer. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot use certain anti-leukemic agents after transplantation and before starting the study therapy. If you are on medications like prednisone, tacrolimus, sirolimus, or ruxolitinib, you may still be eligible.

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

Research has shown that olutasidenib has been safe in earlier studies. One study found that patients with acute myeloid leukemia (AML) who had not responded to other treatments tolerated olutasidenib well, experiencing few severe side effects. Most managed the treatment effectively.

Another study demonstrated that olutasidenib significantly reduced cancer in many patients, with lasting effects. This suggests the treatment is effective and generally safe.

Overall, these studies indicate that olutasidenib is usually well-tolerated and safe. However, all treatments can have side effects, and individual experiences may vary. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for myeloid leukemia?

Researchers are excited about olutasidenib for myeloid leukemia because it takes a unique approach by targeting specific genetic mutations in cancer cells. Unlike traditional chemotherapy, which attacks all rapidly dividing cells, olutasidenib specifically inhibits a mutant form of the IDH1 enzyme found in certain leukemia cells. This targeted action may result in fewer side effects and improved effectiveness for patients with this particular genetic mutation. By honing in on this specific target, olutasidenib offers a promising alternative to existing treatments, potentially leading to better patient outcomes.

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

Research has shown that olutasidenib may effectively treat certain blood cancers with an IDH1 mutation. In studies, olutasidenib has helped many patients with relapsed or hard-to-treat acute myeloid leukemia (a type of blood cancer) achieve complete remission, meaning their cancer signs disappeared. One study found that 48% of patients experienced a significant reduction or disappearance of cancer symptoms. In this trial, participants will receive olutasidenib as maintenance therapy starting 30-120 days after stem cell infusion. These findings suggest that olutasidenib could effectively treat blood cancers following a stem cell transplant. ^{2 4 6 7 8}

Who Is on the Research Team?

Jeremy Ramdial, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with IDH1-mutated myeloid malignancies who have undergone a stem cell transplant. The study aims to understand the safety of using Olutasidenib as a maintenance therapy post-transplant.

Inclusion Criteria

My cancer was IDH1 mutation positive at diagnosis.

Serum bilirubin </= 1.5 x upper limit of normal (ULN) except in subjects with Gilbert's Syndrome in whom total bilirubin must be </= 3.0 mg/dl. Aspartate transaminase (AST) or alanine transaminase (ALT) </= 2.5 x ULN. Alkaline phosphatase </=2.5 x ULN

Negative serum or urine pregnancy test for women with reproductive potential at screening

Exclusion Criteria

I have used specific medications after a transplant and before starting this study.

I had grade II-IV acute GVHD but now have no symptoms or mild symptoms only.

I have moderate or severe chronic graft-versus-host disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive olutasidenib as maintenance therapy after stem cell transplant

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Olutasidenib

Trial Overview The intervention being studied is Olutasidenib, given as maintenance therapy after stem cell transplantation in patients with certain types of blood cancer (myeloid leukemia). This phase II trial focuses on its safety and how well patients tolerate it.

How Is the Trial Designed?

Group I: Olutasidenib Maintenance Therapy Experimental Treatment 1 Intervention

Starting 30-120 days post-stem cell infusion, patients receive olutasidenib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection throughout the study. Additionally, patients may undergo bone marrow aspiration and biopsy, ECHO/MUGA scan and chest x-ray at screening.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

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]

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 phase 2 study involving 82 patients with poor-risk myelodysplastic syndrome (MDS), tipifarnib demonstrated significant efficacy, with a 32% overall response rate, including 15% achieving complete responses and 17% showing hematologic improvements.

The treatment was associated with manageable side effects, primarily grade 3-4 neutropenia (18%) and thrombocytopenia (32%), while severe nonhematologic adverse events were rare, indicating that tipifarnib is a promising option for patients with intermediate- to high-risk MDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter phase 2 study of the farnesyltransferase inhibitor tipifarnib in intermediate- to high-risk myelodysplastic syndrome. Fenaux, P., Raza, A., Mufti, GJ., et al.[2021]

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]

Farnesyltransferase inhibitors (FTIs) are a promising new class of anticancer agents that target the farnesylation process of proteins involved in cancer cell growth and survival, particularly in myeloid leukemia.

FTIs have shown potential in clinical trials for myeloid leukemias, addressing the need for new therapies due to high treatment failure rates and toxicities associated with current treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic efficacy of prenylation inhibitors in the treatment of myeloid leukemia. Morgan, MA., Ganser, A., Reuter, CW.[2013]

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]

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]

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 1 trial involving 84 elderly patients with acute myelogenous leukemia, the combination of tipifarnib and etoposide showed promising results, achieving complete remission in 30% of patients receiving a 14-day regimen.

The combination therapy was well-tolerated, with dose-limiting toxicities noted primarily in the longer 21-day treatment, suggesting that a shorter duration may be more effective and safer for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Active oral regimen for elderly adults with newly diagnosed acute myelogenous leukemia: a preclinical and phase 1 trial of the farnesyltransferase inhibitor tipifarnib (R115777, Zarnestra) combined with etoposide. Karp, JE., Flatten, K., Feldman, EJ., et al.[2021]

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]

The combination of tipifarnib and bortezomib was well tolerated in 11 patients with untreated high-risk myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia (AML), with no maximum tolerated dose reached during the study.

Clinical activity was observed, with three patients achieving a complete response and a median overall survival of 449 days, suggesting that this treatment combination may be effective and warrants further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I clinical trial to study the safety of treatment with tipifarnib combined with bortezomib in patients with advanced stages of myelodysplastic syndrome and oligoblastic acute myeloid leukemia. Muus, P., Langemeijer, S., van Bijnen, S., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40511494/

Effectiveness of olutasidenib versus ivosidenib in patients ... Following weighting, treatment with OLU versus IVO was associated with significantly higher rates of complete response (RD: 0.25; 95%CI: 0.01, ...

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

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

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265025017070

AML-629: A Phase 2 Study of Olutasidenib in Relapsed ... In the pivotal phase 2 trial (NCT02719574), olutasidenib demonstrated a complete remission/complete remission with partial hematologic recovery (CR/CRh) rate of ...

4. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1514/532740/Time-to-Response-and-Overall-Survival-in-Patients

Time to Response and Overall Survival in Patients with mIDH1 ... In the registrational phase 2 trial (NCT02719574), olutasidenib demonstrated an overall response in 48% of patients with relapsed/refractory (R/ ...

5. hematologyadvisor.com hematologyadvisor.com/reports/acute-myeloid-leukemia-aml-olutasidenib-therapy-risk-improved-outcomes/

Early Olutasidenib Therapy Linked to Improved Outcomes ... Now, they presented the efficacy and safety of olutasidenib in patients with R/R mIDH1 AML grouped by the number of prior treatment regimens.

6. 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.

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

Rigel Announces Publication of Data on REZLIDHIA® ... Olutasidenib induced durable composite complete remission in 43.8% of patients relapsed or refractory to prior venetoclax-based regimens ...

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

Olutasidenib in combination with azacitidine induces durable ... Olutasidenib in combination with azacitidine induces durable complete remissions in patients with relapsed or refractory mIDH1 acute myeloid ...