413 Participants Needed

SNDX-5613 for Acute Leukemia

(AUGMENT-101 Trial)

Recruiting at 59 trial locations
SF
AP
DT
SP
Overseen BySyndax Pharmaceuticals
Age: Any Age
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: Syndax Pharmaceuticals
Must be taking: CYP3A4 inhibitors
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests revumenib (also known as SNDX-5613), a new treatment for acute leukemia, a type of blood cancer. The first part of the trial aims to find the optimal dose of revumenib that participants can tolerate. The second part examines the treatment's long-term effectiveness and safety. The trial seeks participants with active acute leukemia, specific genetic changes, and noticeable disease in their bone marrow. As a Phase 1/Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

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

The trial protocol does not specify if you must stop all current medications. However, certain medications, especially those affecting the CYP3A4 enzyme, may affect eligibility. Participants in Phase 1 are grouped based on their use of specific CYP3A4 inhibitors or inducers. Additionally, there are specific washout periods for various treatments, such as 14 days for antileukemia therapy and 7 days for systemic glucocorticoids. It's best to discuss your current medications with the trial team to determine your eligibility.

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

Research shows that revumenib, the treatment under study, has a predictable safety profile. A safety evaluation involving 241 patients with acute leukemia, including both adults and children, found the treatment to be generally well-tolerated.

Earlier studies showed that revumenib led to promising remission rates in patients with a specific type of acute leukemia. The safety data from these studies suggested that side effects were manageable and expected. Although some patients experienced side effects, these were usually not severe.

This trial is still in the early stages, focusing on finding the right dose and assessing the treatment's safety. The fact that revumenib has been studied in many patients already provides some confidence in its safety. However, as with any trial, risks exist, and discussing these with the trial team is crucial.12345

Why do researchers think this study treatment might be promising?

Researchers are excited about SNDX-5613, also known as revumenib, because it offers a novel approach to treating acute leukemia, particularly subtypes like KMT2Ar ALL/MPAL and NPM1m AML. Unlike standard chemotherapy treatments, which often target rapidly dividing cells indiscriminately, revumenib is designed to specifically inhibit the interaction of menin, a protein implicated in the development of certain leukemias. This targeted action could mean more effective treatment with potentially fewer side effects. Additionally, revumenib is administered orally, which is more convenient compared to many current treatments that require intravenous delivery.

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

Research has shown that revumenib, the investigational treatment in this trial, holds promise for treating acute leukemia, particularly in patients with specific genetic changes known as KMT2A-rearranged or NPM1-mutated types. Studies have found that patients with relapsed or hard-to-treat acute leukemia responded well, with some achieving complete remission. Revumenib disrupts a protein interaction that contributes to certain leukemias. This targeted approach has proven safe and effective in various studies. Overall, early results suggest it could be a hopeful treatment for individuals with these specific types of leukemia.23567

Who Is on the Research Team?

AR

Angela R Smith, M.D.

Principal Investigator

Syndax Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for individuals with relapsed/refractory acute leukemias, specifically those with MLL rearrangement or NPM1 mutation. Participants must have a white blood cell count below 25,000/microliter and resolved prior treatment toxicities to ≤Grade 1 (except neuropathy or alopecia). They should not be on certain antifungal drugs unless specified in the study arms, have no active central nervous system disease, HIV viral load, hepatitis B/C, significant cardiac issues within the last six months, severe gastrointestinal conditions affecting drug absorption or serious graft-versus-host disease.

Inclusion Criteria

My AML has relapsed or is resistant, and tests show NPM1c mutation.
I am taking strong antifungal medication like itraconazole.
I am not taking any medication that strongly affects liver enzymes.
See 22 more

Exclusion Criteria

My liver disease is severe, as indicated by my Child-Pugh score.
Detectable human immunodeficiency virus (HIV) viral load within the previous 6 months. Participants with a known history of HIV 1/2 antibodies must have viral load testing prior to study enrollment.
Participants meeting any of the following criteria are not eligible for study participation:
See 13 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1: Dose Escalation

Oral revumenib; sequential cohorts of escalating dose levels to identify the MTD and RP2D

Approximately 1 year

Phase 2: Dose Expansion

Participants enrolled in 3 indication-specific expansion cohorts to determine efficacy, safety, and tolerability

Approximately 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 1 year

What Are the Treatments Tested in This Trial?

Interventions

  • SNDX-5613
Trial Overview The trial tests SNDX-5613 alone or combined with cobicistat to determine its maximum tolerated dose and efficacy in treating specific types of leukemia. Phase 1 focuses on dosage while Phase 2 evaluates effectiveness and safety across different patient groups defined by their genetic mutations related to leukemia.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: RevumenibExperimental Treatment2 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

Syndax Pharmaceuticals

Lead Sponsor

Trials
49
Recruited
2,700+

Published Research Related to This Trial

In a phase 1b/2 trial involving 19 patients with relapsed/refractory acute myeloid leukemia (AML), the combination of azacitidine and the anti-PD-L1 inhibitor avelumab was well tolerated but showed limited clinical activity, with an overall complete remission rate of only 10.5%.
Analysis of bone marrow blasts revealed significantly higher expression of PD-L2 compared to PD-L1, suggesting that PD-L2 may play a key role in the resistance to anti-PD-L1 therapy in AML, indicating a potential target for future treatments.
A phase 1b/2 study of azacitidine with PD-L1 antibody avelumab in relapsed/refractory acute myeloid leukemia.Saxena, K., Herbrich, SM., Pemmaraju, N., et al.[2022]
Revumenib, a menin inhibitor, showed a 63% response rate in a phase II study for patients with relapsed or refractory acute leukemias with KMT2A rearrangements.
In a phase I trial, combining revumenib with three chemotherapies resulted in complete remissions in patients with acute myeloid leukemia, highlighting its potential effectiveness in treatment regimens.
Menin Inhibitors Trigger Leukemia Remissions.[2023]
Acute myeloid leukemia (AML) treatment remains difficult, especially for older patients over 60, who experience high toxicity and low response rates, while younger patients can achieve a 70% response rate with standard therapies.
New targeted therapies, such as oral farnesyltransferase inhibitors, are showing promise in treating refractory AML and are currently in phase II testing, potentially offering better efficacy and safety profiles.
Treatment of acute myeloid leukemia: state-of-the-art and future directions.Stone, RM.[2019]

Citations

1.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/40437770/
Revumenib for Relapsed or Refractory Acute Leukemia ...Conclusions: Revumenib is an innovative targeted treatment with promising activity in r/r acute leukemia with KMT2Ar. Keywords: ALL; AML; ...
Menin Inhibition With Revumenib for KMT2A-Rearranged ...Revumenib, an oral, small molecule inhibitor of the menin-lysine methyltransferase 2A (KMT2A) interaction, showed promising efficacy and safety in a phase I ...
Syndax Presents Positive Revuforj® (revumenib) Data in ...Positive data from multiple trials of Revuforj® (revumenib) as a single-agent and in combination with standard of care agents in patients with acute leukemias.
Menin Inhibitor Revumenib Yields Clinically Meaningful ...Treatment with the menin inhibitor revumenib yielded “clinically meaningful” responses in patients with relapsed or refractory acute myeloid ...
FDA approves revumenib for relapsed or refractory acute ...The main efficacy outcome measures were complete remission rate (CR), CR with partial hematological recovery (CRh), CR+CRh duration, and ...
Syndax Announces FDA Approval of Revuforj® (revumenib) in ...The safety evaluation of Revuforj was based on the FDA's analysis of 241 patients (207 adult and 34 pediatric patients) with R/R acute leukemia ...
Efficacy and Safety of Revumenib in the Treatment of Acute ...This systematic review and meta-analysis aimed to evaluate the efficacy and safety of Revumenib in treating AML with KMT2A rearrangements or ...
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