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

Trial Summary

What is the purpose of this trial?

This phase I trial tests the safety, side effects, and effectiveness of olutasidenib in preventing the return of disease (relapse) in patients who have undergone donor (allogeneic) hematopoietic cell transplant for acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelomonocytic leukemia (CMML) carrying an IDH1 mutation. Olutasidenib is in a class of medications called IDH1 inhibitors. It works by slowing or stopping the growth of cancer cells. Giving olutasidenib may be safe, tolerable and/or effective in preventing relapse in patients with IDH1 mutated AML, MDS or CMML after an allogeneic hematopoietic cell transplant.

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.

What data supports the effectiveness of the drug Olutasidenib for treating leukemia?

Farnesyltransferase inhibitors (FTIs), which are similar to Olutasidenib, have shown promise in treating various blood cancers, including leukemias and myelodysplastic syndromes (MDS). In clinical trials, FTIs have demonstrated the ability to reduce cancerous cells in the bone marrow and improve patient outcomes. ^{1 2 3 4 5}

What safety information is available for Olutasidenib in humans?

Olutasidenib has been studied for safety in patients with acute myeloid leukemia and myelodysplastic syndrome. Common serious side effects include febrile neutropenia (fever with low white blood cell count), anemia (low red blood cell count), thrombocytopenia (low platelet count), and neutropenia (low white blood cell count). Differentiation syndrome, a potentially serious condition, occurred in some patients, with a few severe cases and one fatality reported. ^{6 7 8 9 10}

What makes the drug Olutasidenib unique for treating leukemia?

Olutasidenib is unique because it is an oral drug specifically designed to target and inhibit the mutant isocitrate dehydrogenase 1 (IDH1) enzyme, which is often found in certain types of leukemia. This targeted approach can lead to durable remissions and transfusion independence in patients with relapsed or refractory acute myeloid leukemia (AML) with an IDH1 mutation. ^{6 7 8 11 12}

Research Team

Amandeep Salhotra

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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.

Creatinine clearance of ≥ 30/min/1.73 m^2

Exclusion Criteria

I am not pregnant or breastfeeding.

Prospective participants unable to comply with all study procedures

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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 (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 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]

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 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]

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, 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]

References

1. United States 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. [2014]

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

Identification of molecular predictors of response in a study of tipifarnib treatment in relapsed and refractory acute myelogenous leukemia. [2016]

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

Clinical development of farnesyltransferase inhibitors in leukemias and myelodysplastic syndrome. [2007]

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

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

5. Netherlands pubmed.ncbi.nlm.nih.gov

Inhibitors of signaling in myelodysplastic syndrome. [2009]

6. England 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. [2022]

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

Olutasidenib: First Approval. [2023]

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

Olutasidenib (FT-2102) induces durable complete remissions in patients with relapsed or refractory IDH1-mutated AML. [2023]

9. Spain 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. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Real-world clinical outcomes with enasidenib in relapsed or refractory acute myeloid leukemia. [2022]

11. England 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. [2023]

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

Olutasidenib: from bench to bedside. [2023]