SNDX-5613 + Chemotherapy for Acute Myeloid Leukemia

Recruiting at 27 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

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and clinical activity of SNDX-5613 in combination with intensive chemotherapy in participants with newly diagnosed acute myeloid leukemia (AML) harboring alterations in KMT2A, NPM1, or NUP98 genes.

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.

How is the drug SNDX-5613 different from other treatments for acute myeloid leukemia?

SNDX-5613, also known as Revumenib or Revuforj, is unique because it targets specific genetic mutations in acute myeloid leukemia, offering a more personalized approach compared to traditional chemotherapy. This drug is part of a new wave of treatments focusing on the genetic and molecular aspects of the disease, which may improve outcomes for patients who do not respond well to standard therapies. ^{1 2 3 4 5}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

WT1 and PRAME RNA-loaded dendritic cell vaccine as maintenance therapy in de novo AML after intensive induction chemotherapy. [2023]

2. England pubmed.ncbi.nlm.nih.gov

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

3. France pubmed.ncbi.nlm.nih.gov

Venetoclax Synergistically Enhances the Anti-leukemic Activity of Vosaroxin Against Acute Myeloid Leukemia Cells Ex Vivo. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Emerging therapies for acute myeloid leukemia. [2023]

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

Treatment of Relapsed/Refractory Acute Myeloid Leukemia. [2022]