SNDX-5613 + Gilteritinib for Acute Myeloid Leukemia

Recruiting at 2 trial locations

Overseen By The Ohio State University Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Uma Borate

Must be taking: Strong CYP3A4 inhibitors

Disqualifiers: Acute promyelocytic leukemia, CNS involvement, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days per cycle

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and ideal dosing of two medications, SNDX-5613 (Revumenib or Revuforj) and gilteritinib (Xospata), for treating acute myeloid leukemia (AML) that has returned after treatment or is unresponsive to current therapies. These medications block the actions of certain mutated proteins that promote cancer cell growth. The study targets individuals with AML who have specific genetic mutations associated with their cancer. Eligible participants have AML that has not improved after treatments and possess genetic markers such as FLT3, NPM1, or MLL gene mutations. Participants should not be suitable for intense chemotherapy due to their health status. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications?

The trial requires participants to continue taking certain antifungal medications like itraconazole, ketoconazole, posaconazole, or voriconazole. However, you must not be on any other strong CYP3A4 inhibitors or inducers. For other medications, the protocol does not specify, so it's best to discuss with the trial team.

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

Research has shown that combining the drugs SNDX-5613 and gilteritinib might be safe and manageable for people with a type of acute myeloid leukemia that has certain genetic changes. SNDX-5613 blocks a protein called menin, while gilteritinib targets a protein called tyrosine kinase. These drugs have been studied together. Although specific safety details from these studies are not provided here, their inclusion in a clinical trial suggests they are expected to be reasonably safe. This trial phase focuses on assessing the safety and tolerability of these drugs when used together. Prospective participants should know that monitoring for side effects is a key part of the process. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of SNDX-5613 and gilteritinib for treating Acute Myeloid Leukemia (AML) because it introduces a novel approach to tackling the disease. Unlike standard treatments, which often focus on chemotherapy, this combination targets specific genetic mutations within leukemia cells. SNDX-5613 is a menin inhibitor, which disrupts the interaction between menin and MLL1, a common mutation in AML, while gilteritinib is a FLT3 inhibitor that blocks signals promoting cancer cell growth. Together, these drugs aim to more precisely and effectively hinder cancer progression, offering hope for improved outcomes in patients who may not respond well to current therapies.

What evidence suggests that SNDX-5613 and gilteritinib could be effective for acute myeloid leukemia?

Research has shown that combining SNDX-5613 and gilteritinib, the treatment under study in this trial, may help treat acute myeloid leukemia (AML) that has returned or is resistant to other treatments, particularly in patients with certain gene mutations. SNDX-5613 blocks proteins that promote cancer growth, while gilteritinib targets a specific protein called FLT3 involved in cancer cell growth. Early results from similar studies showed that 40% of patients who had already received many treatments responded to this combination. This suggests that the treatment can slow down or reduce the cancer. These findings offer hope for patients with specific genetic types of AML. ^{1 2 3 6 7}

Who Is on the Research Team?

Uma Borate, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with acute myeloid leukemia that has either returned after treatment or hasn't responded to treatment, and who have specific genetic changes (FLT3 mutation along with an NPM1 mutation or MLL rearrangement).

Inclusion Criteria

Signed informed consent must be obtained prior to participation in the study

Estimated Glomerular Filtration Rate (eGFR) ≥ 60 mL/min/1.73m^2

Ability to communicate with the investigator and comply with study procedures

Exclusion Criteria

I do not have any infections that are currently uncontrolled.

I have had cancer before, but it fits the exceptions.

I have HIV, HBV, or HCV but meet specific health criteria.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive SNDX-5613 orally twice per day and gilteritinib once per day on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

Bone marrow biopsy, aspiration, and blood sample collection throughout the study

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and then every 12 weeks for up to 2 years.

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Gilteritinib
• SNDX-5613

Trial Overview The trial is testing the safety and optimal doses of SNDX-5613 (a menin inhibitor) and gilteritinib (a tyrosine kinase inhibitor), which are drugs designed to block cancer cell growth by targeting certain mutated proteins.

How Is the Trial Designed?

Group I: Treatment (SNDX-5613 and gilteritinib) Experimental Treatment 4 Interventions

Patients receive SNDX-5613 PO BID and gilteritinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow biopsy and aspiration, and blood sample collection throughout the study.

Gilteritinib is already approved in United States, European Union, Japan for the following indications:

Approved in United States as Xospata for:

• Acute myeloid leukemia (AML) with FLT3 mutation

Approved in European Union as Xospata for:

• Acute myeloid leukemia (AML) with FLT3 mutation

Approved in Japan as Xospata for:

• Acute myeloid leukemia (AML) with FLT3 mutation

Who Is Running the Clinical Trial?

Uma Borate

Lead Sponsor

Trials

7

Recruited

310+

Published Research Related to This Trial

Gilteritinib fumarate is a highly selective oral FLT3 inhibitor that has shown significant efficacy in treating relapsed or refractory FLT3-mutated acute myeloid leukemia (AML), with clinical trials indicating higher response rates and longer overall survival compared to traditional salvage chemotherapy.

The drug was well tolerated in clinical trials, with dose-proportional plasma concentrations observed at doses ranging from 20 to 450 mg/day, supporting its safety profile for patients in Japan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacological and clinical profile of gilteritinib (Xospata® tablets 40 mg), a therapeutic agent for relapsed or refractory FLT3-mutated acute myeloid leukemia]. Mori, M., Hidaka, K.[2021]

In a phase IB study involving 80 participants with newly diagnosed FLT3-mutated acute myeloid leukemia (AML), gilteritinib combined with intensive chemotherapy achieved a high composite complete response rate of 89%, indicating strong efficacy in this patient population.

Gilteritinib was well-tolerated as both part of the chemotherapy regimen and as maintenance therapy, with a median overall survival time of 46.1 months, suggesting it is a safe and effective treatment option for patients with FLT3-mutant AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gilteritinib in Combination With Induction and Consolidation Chemotherapy and as Maintenance Therapy: A Phase IB Study in Patients With Newly Diagnosed AML. Pratz, KW., Cherry, M., Altman, JK., et al.[2023]

Gilteritinib has been approved in the EU as a monotherapy for adult patients with relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation, showing a significant improvement in overall survival (9.3 months) compared to salvage chemotherapy (5.6 months) in a phase III study with 371 participants.

The safety profile of gilteritinib is considered manageable, with common side effects including increases in liver enzymes and creatine phosphokinase, as well as gastrointestinal and general symptoms like fatigue and nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency Review of Gilteritinib (Xospata) for the Treatment of Adult Patients with Relapsed or Refractory Acute Myeloid Leukemia with an FLT3 Mutation. Tzogani, K., Røshol, H., Olsen, HH., et al.[2021]

In a phase 3 trial involving 371 patients with relapsed or refractory FLT3-mutated acute myeloid leukemia (AML), gilteritinib significantly improved overall survival compared to salvage chemotherapy, with a median survival of 9.3 months versus 5.6 months.

Gilteritinib also led to higher rates of complete remission (21.1% vs. 10.5%) and had fewer severe adverse events compared to chemotherapy, indicating it is a safer and more effective treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML. Perl, AE., Martinelli, G., Cortes, JE., et al.[2023]

Gilteritinib is a newly approved second-generation FLT3 inhibitor specifically designed for treating relapsed or refractory acute myeloid leukemia (AML) in patients with FLT3 mutations, which are found in about one-third of AML cases.

This treatment targets the FLT3 mutation, which is associated with poor prognosis due to increased tumor growth and reduced cell differentiation, potentially improving outcomes for patients with this challenging form of leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gilteritinib: A Novel FLT3 Inhibitor for Relapsed/Refractory Acute Myeloid Leukemia. Marjoncu, D., Andrick, B.[2021]

Gilteritinib significantly improves overall survival and response rates in adults with relapsed or refractory acute myeloid leukaemia (AML) with FLT3 mutations, as demonstrated in the phase III ADMIRAL trial.

While gilteritinib is effective, it can cause serious side effects like anaemia and febrile neutropenia, but these are generally manageable with dose adjustments, highlighting the importance of monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gilteritinib: A Review in Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukaemia. Kang, C., Blair, HA.[2021]

Gilteritinib, an FLT3 inhibitor approved by the FDA for relapsed or refractory acute myeloid leukemia, showed a 21% complete remission rate and a median overall survival of 9.3 months compared to 5.6 months with standard chemotherapy, indicating its efficacy in improving patient outcomes.

The treatment comes with safety warnings for serious conditions like differentiation syndrome and QT prolongation, necessitating careful monitoring of patients' heart rhythms and blood chemistry during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Gilteritinib for Relapsed or Refractory Acute Myeloid Leukemia with a FLT3 Mutation. Pulte, ED., Norsworthy, KJ., Wang, Y., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06222580

Study Details | NCT06222580 | SNDX-5613 and Gilteritinib ... Giving SNDX-5613 with gilteritinib may be safe, tolerable and/or effective in treating patients with relapsed/refractory FLT3 mutated acute myeloid leukemia.

2. ir.syndax.com ir.syndax.com/news-releases/news-release-details/syndax-announces-compelling-revuforjr-revumenib-and-niktimvotm

Syndax Announces Compelling Revuforj® (revumenib) and ... An oral presentation will report efficacy and safety by leukemia type (AML, ALL, or MPAL) in patients with R/R KMT2Ar acute leukemia in the ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-00036

SNDX-5613 and Gilteritinib for the Treatment of Relapsed ... Giving SNDX-5613 with gilteritinib may be safe, tolerable and/or effective in treating patients with relapsed/refractory FLT3 mutated acute myeloid leukemia.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9983204/

Novel agents and regimens in acute myeloid leukemia Preliminary efficacy data showed that in a similarly heavily pretreated population, the 600 mg dose had meaningful efficacy, with an ORR of 40% ...

5. globenewswire.com globenewswire.com/news-release/2025/11/03/3179404/0/en/Syndax-Announces-Compelling-Revuforj-revumenib-and-Niktimvo-axatilimab-csfr-Data-Accepted-for-Presentation-at-ASH-2025.html

Syndax Announces Compelling Revuforj® (revumenib) and Two poster presentations will report preliminary results from Phase 1 trials of revumenib in combination with intensive chemotherapy in newly ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06222580?term=AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(AREA%5BConditionSearch%5D((LEUKEMIA,%20ACUTE%20MYELOID)%20OR%20(GATA2%20OR%20TERT%20OR%20CHIC2%20OR%20ETV6%20OR%20KIT%20OR%20FLT3%20OR%20NUP214%20OR%20NPM1%20OR%20AF10%20OR%20SH3GL1%20OR%20PICALM%20OR%20CEBPA%20OR%20RUNX1%20OR%20JAK2%20OR%20KRAS%20OR%20DNMT3A%20OR%20LPP))))&rank=1

SNDX-5613 and Gilteritinib for the Treatment of Relapsed ... A group of independent scientists who monitor the safety and scientific integrity of a clinical trial. The DMC can recommend to the sponsor that the trial be ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.24.00826

Menin Inhibition With Revumenib for KMT2A-Rearranged ... Treatment with revumenib resulted in rates of complete remission (CR) or CR with partial hematologic recovery (CR +CRh) that exceeded the null ...