SNDX-5613 + Chemotherapy for Acute Myeloid Leukemia

Recruiting at 44 trial locations

Overseen By Syndax Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Syndax Pharmaceuticals

Must not be taking: Strong CYP3A4 inducers

Disqualifiers: Acute promyelocytic leukemia, CNS leukemia, others

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

Compensation: Varies

Number of Visits: Unknown

76 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new drug, SNDX-5613 (also known as Revumenib or Revuforj), combined with chemotherapy for individuals with a specific type of acute myeloid leukemia (AML). It targets those newly diagnosed with certain gene changes: KMT2A, NPM1, or NUP98. Participants must have confirmed AML and be prepared for intensive chemotherapy. The trial seeks to determine the optimal dose of SNDX-5613 and evaluate its effectiveness with chemotherapy in treating this leukemia type. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial requires that you do not use certain medications, specifically strong CYP3A4 inducers or inhibitors, except for Itraconazole, Ketoconazole, Posaconazole, or Voriconazole. If you are taking any of these, you may need to stop or adjust them before participating.

Is there any evidence suggesting that SNDX-5613 is likely to be safe for humans?

Research has shown that SNDX-5613, also known as revumenib, may help treat acute myeloid leukemia (AML). In studies, 21% of patients achieved complete remission, significantly improving their cancer symptoms. However, 33% of patients with specific gene changes, such as KMT2A, experienced differentiation syndrome (DS), which can cause symptoms like fever and low blood pressure.

Importantly, the FDA has already approved this treatment for certain types of AML, indicating it has undergone safety review in those cases. While side effects may still occur, this approval shows the drug has been carefully evaluated for safety in similar conditions.

For those considering joining a trial, these findings suggest a treatment tested and approved in related situations, although individual experiences may vary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

SNDX-5613 is unique because it targets the menin-MLL1 protein-protein interaction, which is a novel approach for treating acute myeloid leukemia (AML). Unlike standard chemotherapy treatments that broadly attack rapidly dividing cells, SNDX-5613 is designed to specifically disrupt a key pathway involved in the growth of leukemia cells, potentially leading to more effective and targeted treatment. Researchers are excited about this therapy because it could offer a new treatment option with fewer side effects compared to traditional chemotherapy. Additionally, SNDX-5613's use in combination with chemotherapy during different phases (induction, consolidation, and maintenance) may enhance its efficacy and improve patient outcomes.

What evidence suggests that SNDX-5613 might be an effective treatment for acute myeloid leukemia?

Research has shown that SNDX-5613, also known as revumenib, may help treat acute myeloid leukemia (AML) in patients with specific gene mutations. In earlier studies, 23% of patients with NPM1 mutations experienced complete remission, meaning nearly one in four of these patients saw their cancer symptoms disappear completely or almost completely. In this trial, participants will receive SNDX-5613 combined with chemotherapy during the induction and consolidation phases to improve treatment outcomes for people with AML. SNDX-5613 works by blocking certain proteins that promote cancer cell growth. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed acute myeloid leukemia (AML) who have specific genetic changes (KMT2A, NPM1, or NUP98 mutations) and can handle intensive chemotherapy. They should be in decent physical shape (ECOG ≤2), have good liver, kidney, and heart function, and not have been treated for AML before.

Inclusion Criteria

I have AML and haven't received treatment, but can undergo intensive chemotherapy.

My liver, kidneys, and heart are working well.

My diagnosis of AML is confirmed by the latest standards.

Exclusion Criteria

I have stomach or upper gut problems that could affect how I absorb pills.

I currently have an infection that isn't under control.

I am not taking strong CYP3A4 drugs, except for certain antifungals.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Sequential cohorts of escalating dose levels of SNDX-5613 with chemotherapy regimen

Up to 2 cycles (28 days each)

Consolidation

Cohorts receive high-dose cytarabine (HiDAC) chemotherapy followed by SNDX-5613

Up to 4 cycles (28 days each)

Maintenance Monotherapy

Cohorts receive SNDX-5613 as monotherapy

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• SNDX-5613

Trial Overview

The study tests SNDX-5613 combined with a strong chemotherapy regimen called HiDAC to see how safe it is and how well it works against AML. Researchers will monitor participants' reactions to the treatment and check its effectiveness in patients with certain gene alterations.

How Is the Trial Designed?

Group I: SNDX-5613 Experimental Treatment 3 Interventions

Dose Escalation: * Induction: Sequential cohorts of escalating dose levels of SNDX-5613 with chemotherapy regimen. * Consolidation: Cohorts will receive high-dose cytarabine (HiDAC) chemotherapy followed by SNDX-5613. * Maintenance Monotherapy: Cohorts will receive SNDX-5613. Dose Expansion: * Induction: SNDX-5613 at tolerated dose level with chemotherapy regimen. * Consolidation: Cohorts will receive SNDX-5613 with chemotherapy regimen and HiDAC. * Maintenance Monotherapy: Cohorts will receive SNDX-5613.

Who Is Running the Clinical Trial?

Syndax Pharmaceuticals

Lead Sponsor

Trials

49

Recruited

2,700+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1.

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 ...

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.

ir.syndax.com

ir.syndax.com/news-releases/news-release-details/syndax-announces-fda-approval-revuforjr-revumenib-adult-and

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 ...

4.

hematologyadvisor.com

hematologyadvisor.com/news/revuforj-gains-approval-for-r-r-npm1-mutated-aml/

Revuforj Gains Approval for R/R NPM1 Mutated AML

Among 65 evaluable participants with NPM1 mutated AML, the rate of complete remission (CR) plus CR with partial hematological recovery was ...

5.

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.

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.

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).