SNDX-5613 + Chemotherapy for Acute Myeloid Leukemia

Recruiting at 21 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Pregnancy, CNS involvement, others

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

Compensation: Varies

Number of Visits: 2

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for patients with acute myeloid leukemia (AML) who have specific genetic changes. It tests the safety and optimal dose of a drug called SNDX-5613 (also known as Revumenib or Revuforj) when combined with standard chemotherapy drugs, daunorubicin and cytarabine. The aim is to determine if adding SNDX-5613 can shrink or stabilize the cancer more effectively than chemotherapy alone. This trial targets patients with newly diagnosed AML who haven't received prior treatment, except for a specific drug to manage high white blood cell counts. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity 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, but you cannot have received strong or moderate CYP3A4 inhibitors or inducers within 7 days of enrollment. It's important to discuss your current medications with the trial team to ensure there are no interactions.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications, but you cannot have received strong or moderate CYP3A4 inhibitors or inducers within 7 days of enrollment. It's best to discuss your current medications with the trial team.

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

In earlier studies, SNDX-5613, also known as revumenib, showed promise in treating acute myeloid leukemia (AML), particularly in patients with specific genetic changes like NPM1 and MLL/KMT2A. Research has shown that about 33% of patients with these genetic changes experienced differentiation syndrome (DS), which can be managed with proper care.

Revumenib has also received FDA approval for treating AML with certain genetic mutations. This approval indicates that the drug's safety is considered acceptable for some patients, though it applies to a different stage of AML treatment.

The current trial is in its early stages. While previous studies provide some understanding of the drug's safety, researchers are still learning how well the combination of SNDX-5613 with chemotherapy is tolerated. Participants might experience some side effects, and the study aims to find a safe and effective dose. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard chemotherapy treatment for acute myeloid leukemia, which typically involves drugs like daunorubicin and cytarabine, SNDX-5613 introduces a novel approach by targeting the Menin-MLL1 protein interaction. Most treatments focus on killing rapidly dividing cells, but SNDX-5613 specifically disrupts the growth of cancer cells by interfering with a critical process that these cells rely on. Researchers are excited about this treatment because it represents a more targeted attack on the disease, potentially leading to more effective outcomes with fewer side effects.

What evidence suggests that SNDX-5613 combined with chemotherapy could be effective for acute myeloid leukemia?

Research shows that SNDX-5613, also known as revumenib, holds promise for treating acute myeloid leukemia (AML) with specific genetic changes. In earlier studies, about 21% of patients achieved complete remission, where all signs of cancer disappeared, or experienced partial recovery of blood counts. Nearly one in five patients saw significant improvement in their cancer. In this trial, participants will receive SNDX-5613 combined with standard chemotherapy drugs daunorubicin and cytarabine. The treatment blocks signals that help cancer cells survive. These findings suggest that SNDX-5613 could enhance standard chemotherapy, potentially shrinking or controlling cancer for longer periods. ^{1 2 4 6 7}

Who Is on the Research Team?

Alice Mims

Principal Investigator

Ohio State University Comprehensive Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with newly diagnosed acute myeloid leukemia that has specific gene changes (NPM1 or MLL/KMT2A) and are fit for intensive chemotherapy. Participants must have good organ function, an ECOG performance status of <=2, and if HIV-positive, they need undetectable viral load on effective therapy. Those with chronic hepatitis B or C must be on suppressive therapy or cured.

Inclusion Criteria

I agree to use birth control during the study.

Specific laboratory values within defined ranges (e.g., total bilirubin, AST/ALT, GFR)

My heart functions within specific health parameters.

Exclusion Criteria

Patients with Down Syndrome

History of allergic reactions to specific compounds

Uncontrolled intercurrent illness that would make participation unsafe

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction

Patients receive revumenib orally every 12 hours on days 2-28, daunorubicin intravenously on days 1-3, and cytarabine by continuous IV infusion on days 1-7

6 weeks

Multiple visits for drug administration and monitoring

Re-Induction

Patients receive revumenib orally every 12 hours on days 2-28, daunorubicin intravenously on days 1-2, and cytarabine by continuous IV infusion on days 1-5

6 weeks

Multiple visits for drug administration and monitoring

Consolidation

Patients receive revumenib orally every 12 hours on days 2-28 and cytarabine by continuous IV infusion on days 1-3

6 weeks

Multiple visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1-2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• SNDX-5613

Trial Overview

The trial is testing the safety and optimal dose of SNDX-5613 added to standard chemo drugs Daunorubicin and Cytarabine in patients with certain genetic types of acute myeloid leukemia. The goal is to see if this new combination can better shrink or control cancer compared to standard treatment alone.

How Is the Trial Designed?

Group I: Treatment (revumenib, daunorubicin, cytarabine) Experimental Treatment 8 Interventions

See Detailed Description.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The combination of vosaroxin and venetoclax synergistically induces apoptosis in acute myeloid leukemia (AML) cell lines and primary patient samples, suggesting a potent anti-leukemic effect.

This combination treatment effectively targets AML progenitor cells while sparing normal hematopoietic progenitor cells, indicating a potentially safer therapeutic option for elderly patients with AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax Synergistically Enhances the Anti-leukemic Activity of Vosaroxin Against Acute Myeloid Leukemia Cells Ex Vivo. Liu, F., Knight, T., Su, Y., et al.[2020]

In a study involving 20 patients with acute myeloid leukemia (AML) in first complete remission, the autologous dendritic cell vaccine FDC101 was well tolerated, with only mild side effects, and resulted in 55% of patients remaining in remission over a 2-year period.

The five-year overall survival rate was 75%, indicating that this vaccine therapy could be a promising maintenance treatment for AML patients not eligible for stem cell transplantation, especially for older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

WT1 and PRAME RNA-loaded dendritic cell vaccine as maintenance therapy in de novo AML after intensive induction chemotherapy. Fløisand, Y., Remberger, M., Bigalke, I., et al.[2023]

Acute myeloid leukemia (AML) treatment has seen little change in 40 years, but new agents like IDH inhibitors and antibody-drug conjugates show promise in improving outcomes, either alone or with traditional chemotherapy.

A variety of novel therapies, including cytotoxic agents, epigenetic modifiers, and targeted inhibitors, are currently being tested in clinical trials, indicating a potential shift in AML management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging therapies for acute myeloid leukemia. Saygin, C., Carraway, HE.[2023]

The VALOR study, involving 711 patients, showed that the combination of vosaroxin and cytarabine resulted in better complete remission rates and survival for older patients (≥60 years) with relapsed/refractory acute myeloid leukemia (AML) compared to placebo/cytarabine.

Vosaroxin demonstrated a safety profile similar to existing AML treatments, making it a promising option for older patients who often face poor outcomes due to comorbidities and unfavorable cytogenetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vosaroxin in relapsed/refractory acute myeloid leukemia: efficacy and safety in the context of the current treatment landscape. Sedov, V., Stuart, RK.[2020]

Current standard chemotherapy cures about 40-45% of younger adults and 10-20% of older adults with acute myeloid leukemia (AML), but the prognosis is poor for those with relapsed or refractory disease, where cure rates are only around 10%.

Recent advances in understanding the genetic and epigenetic factors of AML have led to the development of new targeted therapies, such as CPX-351 and venetoclax, which may improve treatment outcomes, especially when combined with conventional therapies and evaluated for allogeneic stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Relapsed/Refractory Acute Myeloid Leukemia. Bose, P., Vachhani, P., Cortes, JE.[2022]

Citations

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Syndax Announces FDA Approval of Revuforj® (revumenib) in ...

The rate of complete remission (CR) plus CR with partial hematological recovery (CRh) was 23% (15/65 pts; 95% CI: 14%, 35%). The median time to ...

2.

fda.gov

fda.gov/drugs/resources-information-approved-drugs/fda-approves-revumenib-relapsed-or-refractory-acute-myeloid-leukemia-susceptible-npm1-mutation

FDA approves revumenib for relapsed or refractory acute ...

Efficacy was evaluated in a single-arm cohort of an open-label, multicenter trial (SNDX-5613-0700, NCT04065399; AUGMENT-101). A susceptible ...

3.

revuforj.com

revuforj.com/trial-results/

Trial Results | Revuforj® (revumenib) Official Patient Site

In the clinical trial, 21% of people (22 out of 104) achieved complete remission (CR) or complete remission with a partial hematologic recovery (CRh).

4.

ajmc.com

ajmc.com/view/revumenib-shows-efficacy-in-patients-with-aml-and-genetic-alterations

Revumenib Shows Efficacy in Patients With AML and ...

Revumenib shows promise for high-risk patients with acute myeloid leukemia (AML) with specific genetic mutations, demonstrating efficacy with no new safety ...

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ir.syndax.com

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

Syndax Announces Compelling Revuforj® (revumenib) and ...

Among those with a KMT2A translocation, DS occurred in 33% of patients with acute myeloid leukemia (AML), 33% of patients with mixed-phenotype ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06226571

NCT06226571 | A Study of SNDX-5613 in Combination ...

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and clinical activity of SNDX-5613 in combination with intensive ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11060303/

Revumenib (SNDX-5613): a promising menin inhibitor for ...

Revumenib (SNDX-5613): a promising menin inhibitor for the management of relapsed and refractory acute myeloid leukaemia (AML)