Olutasidenib for Chronic Myelomonocytic Leukemia

Overseen By Kelly Chien, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Hepatitis B, Hepatitis C, HIV, 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: 12 months

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests olutasidenib, a drug that may help control certain blood disorders, specifically CCUS, MDS, and CMML, while also assessing its safety. The focus is on individuals with these conditions who have a specific genetic mutation in IDH1. A suitable candidate for this trial might be someone diagnosed with one of these disorders and experiencing low blood cell counts that affect daily life. Participants will take olutasidenib capsules twice a day on an empty stomach. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, hydroxyurea is allowed without a washout period, so you may be able to continue some medications. It's best to discuss your specific medications with the trial team.

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

Research shows that olutasidenib is generally safe for patients. Studies have found that people with certain blood cancers, such as AML (acute myeloid leukemia) and MDS (myelodysplastic syndromes), tolerate it well. In earlier research, olutasidenib helped patients achieve remission, significantly improving their symptoms.

Importantly, the FDA has approved olutasidenib for a type of leukemia, providing some confidence in its safety. However, like any treatment, it may cause side effects. Overall, early findings suggest that olutasidenib is a promising option with a manageable safety profile for individuals with certain blood conditions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Olutasidenib is unique because it targets a specific mutation in the IDH1 gene, which is not typically addressed by standard treatments for chronic myelomonocytic leukemia (CMML). Most current treatments focus on controlling symptoms or slowing the progression of the disease, often using chemotherapy or hypomethylating agents. However, olutasidenib directly inhibits the mutated enzyme, potentially altering the disease's course by targeting the cancer at the genetic level. Researchers are excited because this approach could offer a more precise and effective way to treat CMML, potentially improving outcomes for patients who have limited options.

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

Research has shown that olutasidenib, the investigational treatment in this trial, yields promising results for certain blood disorders. In previous studies, it helped patients with acute myeloid leukemia (AML) who had a specific mutation (mIDH1) achieve long-lasting remissions, allowing many to stop needing blood transfusions. Olutasidenib has also effectively treated myelodysplastic syndrome (MDS), leading to quick improvements. This suggests it might also benefit conditions like chronic myelomonocytic leukemia (CMML). The drug targets a specific enzyme mutated in these diseases, helping control the growth of abnormal cells. ^{1 3 4 6 7}

Who Is on the Research Team?

Kelly Chien, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with specific blood disorders: Clonal Cytopenia of Undetermined Significance (CCUS), lower-risk Myelodysplastic Syndromes (MDS), or Chronic Myelomonocytic Leukemia (CMML). Participants must have a mutation in the IDH1 gene. Detailed eligibility criteria are not provided, but typically include age, health status, and previous treatments.

Inclusion Criteria

My cancer has a specific IDH1 mutation.

My kidney function is within the required range.

Negative serum or urine pregnancy test if female of childbearing potential

Exclusion Criteria

I do not have any severe uncontrolled health or mental conditions.

Participant with white blood cell count > 25 x109/L

I cannot take pills by mouth or have a gut condition affecting drug absorption.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive olutasidenib monotherapy, taking capsules twice daily

12 months

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Olutasidenib

Trial Overview The study is testing Olutasidenib's effectiveness in controlling CCUS, MDS, and CMML in patients with an IDH1 mutation. It's a Phase 2 trial which means it focuses on the drug’s efficacy and monitoring its safety.

How Is the Trial Designed?

Group I: Olutasidenib Experimental Treatment 1 Intervention

Participants will take capsules of olutasidenib 2 times each day while you are on study. Each dose should be taken about 12 hours apart at least 1 hour before or 2 hours after a meal.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Rigel Pharmaceuticals

Industry Sponsor

Trials

37

Recruited

4,000+

Published Research Related to This Trial

Chronic myelomonocytic leukemia (CMML) is characterized by specific gene mutations, with TET2, SRSF2, and ASXL1 being the most common, and certain mutations like ASXL1 negatively impacting overall survival.

Current treatment options, including hypomethylating agents and allogeneic stem cell transplants, show suboptimal results, but ongoing clinical trials targeting epigenetic and signaling pathway abnormalities offer potential for improved outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic Myelomonocytic Leukemia: a Genetic and Clinical Update. McCullough, KB., Patnaik, MM.[2018]

Chronic myelomonocytic leukemia (CMML) is characterized by specific gene mutations and cytogenetic abnormalities that can help stratify patients into risk groups, guiding treatment decisions; common mutations include TET2, SRSF2, and ASXL1, with ASXL1 mutations linked to worse outcomes.

Allogeneic stem cell transplantation is the preferred treatment for younger patients with poor prognostic factors, while hypomethylating agents may be considered for those ineligible for transplantation, highlighting the need for a consensus on treatment guidelines and response criteria for clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic myelomonocytic leukemia prognostic classification and management: evidence base and current practice. Selimoglu-Buet, D., Solary, E.[2021]

Chronic myelomonocytic leukemia (CMML) is now recognized as a distinct category that combines features of myelodysplastic syndromes and myeloproliferative disorders, with a new prognostic score developed to classify patients into four groups based on their prognosis.

Recent research highlights the role of angiogenesis and specific genetic factors, such as tyrosine kinase fusion genes, in CMML, suggesting that targeted therapies like imatinib mesylate and antiangiogenic agents could be effective, although more studies are needed to explore these treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CMML: a biologically distinct myeloproliferative disease. Cortes, J.[2006]

Chronic myelomonocytic leukemia (CMML) has a poor prognosis with a median overall survival of only 2-3 years, and current treatments like hypomethylating agents do not significantly change the disease's natural course.

New therapeutic strategies, including combination therapies with novel agents such as sotatercept and ruxolitinib, are being explored in clinical trials, highlighting the need for innovative approaches to effectively target CMML and improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increasing recognition and emerging therapies argue for dedicated clinical trials in chronic myelomonocytic leukemia. Renneville, A., Patnaik, MM., Chan, O., et al.[2023]

Chronic myelomonocytic leukemia (CMML) has a poor prognosis with a median overall survival of about 2 years and a significant risk of transforming into acute myeloid leukemia (15-20% over 5 years), highlighting the need for better understanding and treatment options.

Current treatment options are limited, with only two FDA-approved drugs (5-azacitidine and decitabine) and allogeneic hematopoietic stem cell transplantation being the only curative approach, which carries high risks of complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in chronic myelomonocytic leukemia and future prospects: Lessons learned from precision genomics. Mangaonkar, AA., Patnaik, MM.[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. clinicaltrials.gov clinicaltrials.gov/study/NCT06566742?term=OLUTASIDENIB&rank=1

A Phase 2 Study Evaluating Olutasidenib in Patients With ... To learn if olutasidenib can help to control CCUS, MDS, and/or CMML. The safety of the drug will also be studied. Detailed Description. Primary Objectives - To ...

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

Treatment Patterns and Outcomes of Olutasidenib in ... Olutasidenib, a mutated IDH1 (mIDH1) inhibitor, was approved by the FDA for the treatment of adult patients with R/R mIDH1 AML, based on a Phase 2, open-label, ...

4. ashpublications.org ashpublications.org/blood/article/134/Supplement_1/674/426552/Olutasidenib-FT-2102-Induces-Rapid-Remissions-in

Olutasidenib (FT-2102) Induces Rapid Remissions in Patients ... Olutasidenib (FT-2102) Induces Rapid Remissions in Patients with IDH1-Mutant Myelodysplastic Syndrome: Results of Phase 1/2 Single Agent ...

5. oncology-central.com oncology-central.com/olutasidenib-offers-new-hope-for-myelodysplastic-syndrome-patients/

Olutasidenib offers new hope for myelodysplastic ... A new trial has found that olutasidenib is highly effective in treating certain cases of myelodysplastic syndrome.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06543381

NCT06543381 | Olutasidenib for the Treatment of Patients ... Giving olutasidenib may be safe, tolerable and/or effective in preventing relapse in patients with IDH1 mutated AML, MDS or CMML after an allogeneic ...

7. trialx.com trialx.com/clinical-trials/listings/304294/olutasidenib-for-the-treatment-of-patients-with-idh1-mutated-aml-mds-or-cmml-after-donor-hematopoietic-cell-transplant/

Olutasidenib for the Treatment of Patients With IDH1 ... Giving olutasidenib may be safe, tolerable and/or effective in preventing relapse in patients with IDH1 mutated AML, MDS or CMML after an ...