SNDX-5613 + Chemotherapy for Acute Myeloid Leukemia

Recruiting at 16 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

Trial Summary

What is the purpose of this trial?

This phase Ib trial tests the safety, side effects, and best dose of SNDX-5613 when given in combination with the standard chemotherapy treatment (daunorubicin and cytarabine) in treating patients with newly diagnosed acute myeloid leukemia that has changes in the NPM1 gene or MLL/KMT2A gene. SNDX-5613 blocks signals passed from one molecule to another inside cancer cells that are needed for cancer cell survival. Drugs used in chemotherapy, such as daunorubicin and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding SNDX-5613 to the standard chemotherapy treatment may be able to shrink or stabilize the cancer for longer than the standard chemotherapy treatment alone.

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.

How is the drug SNDX-5613 (Revumenib, Revuforj) different from other treatments for acute myeloid leukemia?

SNDX-5613 (Revumenib, Revuforj) is unique because it targets specific genetic mutations in acute myeloid leukemia, offering a more personalized approach compared to traditional chemotherapy, which often has high relapse rates and is less effective in older patients. ^{1 2 3 4 5}

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

SNDX-5613 (Revumenib) is unique because it targets specific genetic mutations in acute myeloid leukemia, offering a more personalized approach compared to traditional chemotherapy, which often has high relapse rates and is less effective in older patients. ^{1 2 3 4 5}

Research Team

Alice Mims

Principal Investigator

Ohio State University Comprehensive Cancer Center LAO

Eligibility Criteria

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

Pregnant or breastfeeding women

Timeline

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)

Treatment Details

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.

Participant Groups

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+

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]

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 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]

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

Emerging therapies for acute myeloid leukemia. [2023]

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

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

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

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