Ziftomenib + Quizartinib for Acute Myeloid Leukemia

Overseen By Ghayas Issa, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Menin inhibitors

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

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

Compensation: Varies

Number of Visits: Unknown

44 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests an all-oral treatment combining Ziftomenib and Quizartinib to determine its safety and effectiveness for certain types of acute myeloid leukemia (AML). The research targets AML subtypes with specific genetic changes, accounting for about 40-45% of cases. This trial may suit individuals with AML or related leukemia that has recurred or is unresponsive to current treatments, particularly those with genetic markers like NPM1mt, KMT2Ar, or NUP98r. Participants should be able to swallow pills and have a white blood cell count below 25,000. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, the use of other chemotherapeutic or anti-leukemic agents is not allowed during the study, except for certain cases like intrathecal chemotherapy for CNS leukemia or hydroxyurea for rapidly proliferative disease.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that ziftomenib, when used alone, is generally safe and well-tolerated in patients with acute myeloid leukemia (AML). Some studies are examining its combination with another drug, quizartinib, to determine the optimal dose for treating AML. While information on the safety of using these two drugs together is still being collected, each drug has shown promise individually.

Ziftomenib has been tested with standard treatments and has shown early signs of safety. Quizartinib has been studied with intensive chemotherapy in other trials and has demonstrated safety and tolerability.

This is an early-phase study, focusing primarily on the safety of the combination. Although specific numbers are not yet available, early research suggests the treatment might be manageable for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Ziftomenib + Quizartinib for Acute Myeloid Leukemia because this combination introduces a novel approach to tackling the disease. Unlike standard treatments such as chemotherapy and stem cell transplants, Ziftomenib is designed to specifically target and disrupt the function of menin, a protein involved in the development of leukemia cells. Quizartinib complements this by inhibiting FLT3, a common mutation found in leukemia patients, potentially leading to more effective cancer cell eradication. Together, these mechanisms aim to offer a more precise and potentially effective treatment option compared to existing therapies.

What evidence suggests that this trial's treatments could be effective for acute myeloid leukemia?

Research has shown that combining two drugs, ziftomenib and quizartinib, might help treat certain types of acute myeloid leukemia (AML). In this trial, participants will receive the combination of these drugs. Ziftomenib has shown promise in treating AML with NPM1 mutations, leading to strong and lasting improvements by targeting leukemia cells that depend on a protein called menin. Early studies suggest that using ziftomenib with quizartinib, which blocks a specific enzyme in cancer cells, enhances its effectiveness. This combination aims to treat a wide range of AML types, offering hope for better treatments. ^{1 3 6 7 8}

Who Is on the Research Team?

Ghayas Issa, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults with Acute Myeloid Leukemia (AML) or related conditions, who haven't responded to previous treatments. They must have certain blood counts, organ functions within set limits, and no major heart issues in the past 6 months. Participants need to be able to take pills and agree to use contraception if they can have children.

Inclusion Criteria

Baseline ejection fraction must be > 40%

My white blood cell count is below 25,000/μL.

My liver is functioning within the required limits for the trial.

Exclusion Criteria

I am not on chemotherapy, except for specific allowed treatments.

I have been treated with a menin inhibitor before.

I have an active hepatitis B, hepatitis C, or HIV infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation and Expansion

Participants receive ziftomenib in combination with quizartinib to determine the recommended phase 2 dose and assess safety and maximum tolerated dose

12 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Quizartinib
• Ziftomenib

Trial Overview The trial is testing a combination of two oral drugs, Ziftomenib and Quizartinib, for AML treatment. It aims to provide an effective therapy option for about 40-45% of AML subtypes that share specific genetic changes.

How Is the Trial Designed?

Group I: Ziftoenib + Quizartinib Q4W Experimental Treatment 2 Interventions

Participants will be randomized to study

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

In a study of 202 older patients with acute myeloid leukemia (AML) who were not suitable for intensive chemotherapy, the addition of quizartinib to low-dose ara-C (LDAC) did not improve overall survival for the entire group, but it significantly enhanced response rates in patients with the FLT3-ITD mutation.

For the 27 FLT3-ITD patients, those receiving quizartinib plus LDAC had a median overall survival of 13.7 months compared to 4.2 months for those on LDAC alone, indicating that quizartinib could be a promising option for improving outcomes in this specific subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized evaluation of quizartinib and low-dose ara-C vs low-dose ara-C in older acute myeloid leukemia patients. Dennis, M., Thomas, IF., Ariti, C., et al.[2022]

In a phase 3 trial involving 367 patients with relapsed or refractory FLT3-ITD-positive acute myeloid leukaemia, treatment with quizartinib resulted in a longer median overall survival of 6.2 months compared to 4.7 months for those receiving standard chemotherapy, indicating a significant survival benefit.

Quizartinib demonstrated a manageable safety profile, with common serious adverse events being similar to those seen in chemotherapy, suggesting it could be a new standard of care for patients with this aggressive form of leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quizartinib versus salvage chemotherapy in relapsed or refractory FLT3-ITD acute myeloid leukaemia (QuANTUM-R): a multicentre, randomised, controlled, open-label, phase 3 trial. Cortes, JE., Khaled, S., Martinelli, G., et al.[2020]

In a study involving 93 healthy subjects, quizartinib showed a significant increase in plasma concentration when coadministered with the strong CYP3A inhibitor ketoconazole, indicating that dose adjustments may be necessary to avoid potential toxicity.

The study found that quizartinib had a low incidence of related adverse events (5.4%), with no serious adverse events or deaths reported, suggesting it is generally safe when administered alone or with moderate CYP3A inhibitors like fluconazole.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of CYP3A inhibitors on the pharmacokinetics of quizartinib, a potent and selective FLT3 inhibitor, and its active metabolite. Li, J., Kankam, M., Trone, D., et al.[2021]

In a phase III trial, the FLT3 inhibitor quizartinib showed a survival benefit compared to traditional chemotherapy in patients with relapsed or refractory FLT3-mutant acute myeloid leukemia.

The promising results from quizartinib suggest it may become a first-line treatment option for this type of leukemia, pending outcomes from ongoing studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quizartinib Bests Chemo for FLT3-Mutant AML. [2019]

Quizartinib, a selective FLT3 inhibitor, demonstrated significant efficacy in treating relapsed or refractory acute myeloid leukaemia, particularly in patients with FLT3-ITD mutations, with 56% of FLT3-ITD-positive patients in cohort 1 achieving composite complete remission.

The treatment was generally well tolerated, although serious adverse events occurred in a notable percentage of patients, including febrile neutropenia and QTc prolongation, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quizartinib, an FLT3 inhibitor, as monotherapy in patients with relapsed or refractory acute myeloid leukaemia: an open-label, multicentre, single-arm, phase 2 trial. Cortes, J., Perl, AE., Döhner, H., et al.[2023]

Citations

1. ir.kuraoncology.com ir.kuraoncology.com/news-releases/news-release-details/kura-oncology-and-kyowa-kirin-launch-clinical-trial-evaluating

Kura Oncology and Kyowa Kirin Launch Clinical Trial ... “Preclinical data demonstrate that ziftomenib synergizes with FLT3 inhibitors such as quizartinib, potentially enhancing activity without ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-00080

Ziftomenib and Quizartinib for the Treatment of Relapsed or ... Giving ziftomenib in combination with quizartinib may be safe, tolerable, and/or effective in treating patients with relapsed or refractory AML.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05735184

NCT05735184 | A Study to Investigate the Safety and ... The purpose of this study is to assess the safety, tolerability, and early signs of efficacy of ziftomenib in combination with SOC drugs to treat AML. Official ...

4. targetedonc.com targetedonc.com/view/final-trial-data-shows-success-for-ziftomenib-in-npm1-aml

Final Trial Data Show Success for Ziftomenib in NPM1 AML Ziftomenib showed significant efficacy in relapsed/refractory NPM1-mutant AML, achieving deep, durable responses in the KOMET-001 trial. The ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123081569

Komet-008: A Phase 1 Study to Determine the Safety and ... Preclinical data have demonstrated ziftomenib's ability to target multiple types of menin-dependent AML clones, and that the antitumor activity of ziftomenib ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05735184

NCT05735184 | A Study to Investigate the Safety and ... The purpose of this study is to assess the safety, tolerability, and early signs of efficacy of ziftomenib in combination with SOC drugs to treat AML. Official ...

7. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/1553/503085/Komet-008-A-Phase-1-Study-to-Determine-the-Safety

Komet-008: A Phase 1 Study to Determine the Safety and ... An ongoing Phase 1/2 study (KOMET-001) in R/R AML has demonstrated that ziftomenib monotherapy is safe and well tolerated and that the clinical activity at the ...

8. mayo.edu mayo.edu/research/clinical-trials/cls-20570436

Clinical Trials The purpose of this study is to assess the safety, tolerability, and early signs of efficacy of ziftomenib in combination with SOC drugs to ...