RVU120 for Acute Myeloid Leukemia

(RIVER-52 Trial)

Not currently recruiting at 59 trial locations

Overseen By Head of Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ryvu Therapeutics SA

Must not be taking: Immunosuppressants, Metabolism-interfering substances

Disqualifiers: CNS leukemia, APL, HIV, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 21-day cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, RVU120, for individuals with certain blood cancers, specifically acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (HR-MDS), who have not responded to other treatments. The main goal is to determine if RVU120 is safe and effective against these cancers. Participants will take RVU120 capsules every other day for a set period to assess its efficacy and any side effects. This trial may suit individuals whose AML or HR-MDS has returned or worsened after previous treatments and who have no other treatment options. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications, herbal supplements, or other substances that might interfere with the study drug.

Is there any evidence suggesting that RVU120 is likely to be safe for humans?

Research has shown that RVU120 is promising in terms of safety for people with acute myeloid leukemia (AML). Previous studies found that most people tolerate it well, experiencing no severe side effects. Some evidence also highlights its strong ability to fight cancer, which is encouraging. However, like all treatments, it can cause some side effects. Discussing expectations and concerns with a doctor is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for acute myeloid leukemia (AML), which often involve chemotherapy or targeted therapies like FLT3 inhibitors, RVU120 is unique because it targets a different pathway. RVU120 is an oral capsule that specifically inhibits the CDK8/19 enzymes, which are involved in regulating gene expression critical to cancer cell survival and proliferation. Researchers are excited about RVU120 because it offers a new mechanism of action that could potentially overcome resistance seen with current therapies, providing a fresh option for patients who don't respond well to existing treatments.

What evidence suggests that RVU120 might be an effective treatment for acute myeloid leukemia?

Research has shown that RVU120, a new treatment, has promising effects against cancer in patients with acute myeloid leukemia (AML). In this trial, participants will receive RVU120 as a single agent. Studies indicate that RVU120, particularly when combined with other treatments like venetoclax, can be effective for AML that has returned or is difficult to treat. This treatment targets specific proteins that aid cancer cell growth. Early results suggest that RVU120 can slow cancer progression in these patients and shows potential for those who haven't succeeded with other therapies. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with relapsed or refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (HR-MDS) who have no other treatment options. Participants must be in relatively good health, with an ECOG performance status of 0 to 2, and meet certain blood count and coagulation criteria.

Inclusion Criteria

I am willing to sign a consent form and follow study procedures.

I have been diagnosed with AML or high-risk MDS according to the latest criteria.

My AML has returned or didn't respond to treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

3 weeks

Treatment

Participants receive RVU120 oral capsules every other day on Days 1-13 of each 21-day cycle

21-day cycles

End of Treatment

Approximately 30 days after the last dose to assess safety and tolerability

4 weeks

Follow-up

Participants are monitored for progression and survival status every 3 months

12 months

What Are the Treatments Tested in This Trial?

Interventions

• RVU120

Trial Overview The study tests RVU120's safety, tolerability, anti-tumor activity, pharmacokinetics (how the drug moves through the body), and pharmacodynamics (the drug's effects on the body). It has two parts: first to find a safe dosage and measure tumor response; second to confirm these findings in more patients.

How Is the Trial Designed?

Group I: RVU120 single agent Experimental Treatment 1 Intervention

RVU120 oral capsules administered at dose of 250 mg every other day on Days 1-13 of each 21-day cycle of treatment.

Who Is Running the Clinical Trial?

Ryvu Therapeutics SA

Lead Sponsor

Trials

7

Recruited

870+

Published Research Related to This Trial

In a study of 167 patients with acute erythroleukemia (AEL), specific cell surface markers (CD13, CD33, CD117, and CD34) were found to be highly expressed, indicating unique biological characteristics of AEL.

Allogeneic hematopoietic stem cell transplantation significantly improved overall survival compared to chemotherapy alone, highlighting its potential as a more effective treatment option for AEL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Characteristics and Prognosis of 167 Cases of Acute Erythroleukemia. Ma, ZQ., Pan, JH., Jing, DX., et al.[2020]

In a phase 1 study involving 23 patients with relapsed/refractory acute myeloid leukemia (AML), the combination of selinexor with mitoxantrone, etoposide, and cytarabine showed an overall response rate of 43%, with 26% of patients achieving complete remission.

The maximum tolerated dose of selinexor was determined to be 30 mg/m2 due to dose-limiting side effects, including hyponatremia, indicating that while the treatment is promising, careful monitoring for toxicity is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of selinexor in combination with salvage chemotherapy in Adults with relapsed or refractory Acute myeloid leukemia. Bhatnagar, B., Zhao, Q., Mims, AS., 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]

In a phase II study involving 175 patients aged 60 and older with relapsed/refractory acute myeloid leukemia, selinexor did not significantly improve overall survival compared to physician's choice treatment, with median survival times of 3.2 months versus 5.6 months.

Patients treated with selinexor experienced a higher incidence of serious adverse events, including thrombocytopenia and febrile neutropenia, indicating a need for careful patient selection and monitoring in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 2:1 randomized, open-label, phase II study of selinexor vs. physician's choice in older patients with relapsed or refractory acute myeloid leukemia. Sweet, K., Bhatnagar, B., Döhner, H., et al.[2022]

In a phase I trial involving 20 patients with acute myeloid leukemia (AML), the combination of selinexor with high-dose cytarabine and mitoxantrone was found to be feasible and tolerable, with no dose-limiting toxicities observed at the target dose of 80 mg.

The treatment resulted in a 70% overall response rate, with 50% of patients achieving complete remission, indicating promising efficacy for selinexor in combination therapy for AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of selinexor in combination with high-dose cytarabine and mitoxantrone for remission induction in patients with acute myeloid leukemia. Wang, AY., Weiner, H., Green, M., et al.[2022]

A patient with a variant form of acute promyelocytic leukemia (APL) and a FLT3-ITD mutation achieved complete molecular remission using a combination of all-trans retinoic acid (ATRA), arsenic trioxide (ATO), and idarubicin (IDA), rather than the standard treatment protocol.

The study suggests that incorporating a FLT3 inhibitor in the treatment of APL patients with FLT3-ITD mutations may help prevent complications like differentiation syndrome and coagulopathy, which were experienced by the patient but managed effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Favorable outcome of PML-RARα short isoform and FLT3-ITD mutation in a patient with several adverse prognostic markers: A case report. Bafail, MA., AlTahan, R., Samman, MA., et al.[2023]

In a phase I study involving 25 older and relapsed or refractory AML patients, the combination of the oral exportin-1 inhibitor selinexor and decitabine showed a 40% overall response rate, indicating preliminary clinical activity.

The recommended dose of selinexor was established at 60 mg twice weekly, with manageable safety concerns, including significant but tolerable side effects like hyponatremia and febrile neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selinexor in combination with decitabine in patients with acute myeloid leukemia: results from a phase 1 study. Bhatnagar, B., Zhao, Q., Mims, AS., et al.[2021]

Selinexor, a selective inhibitor of nuclear export, was found to be safe and well-tolerated in a phase 1 study involving 95 patients with relapsed or refractory acute myeloid leukemia (AML), with manageable side effects primarily being mild gastrointestinal and constitutional toxicities.

The study showed that 14% of evaluable patients achieved an objective response, leading to significantly improved progression-free survival (5.1 months vs. 1.3 months) and overall survival (9.7 months vs. 2.7 months) compared to nonresponders, indicating its potential efficacy as a treatment for AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 clinical trial of single-agent selinexor in acute myeloid leukemia. Garzon, R., Savona, M., Baz, R., et al.[2021]

Acute promyelocytic leukemia (APL) is characterized by a specific genetic mutation (PML-RARA) resulting from a translocation between chromosomes 15 and 17, which disrupts normal blood cell development.

Current treatments for APL, particularly the use of all-trans retinoic acid and arsenic trioxide, have led to remarkable success rates, achieving complete remission in 90%-100% of patients and overall survival rates between 86% and 97%, contrasting sharply with the poorer outcomes in non-promyelocytic acute myeloid leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retinoic acid and arsenic trioxide in the treatment of acute promyelocytic leukemia: current perspectives. McCulloch, D., Brown, C., Iland, H.[2022]

Citations

1. ryvu.com ryvu.com/press-release/ryvu-therapeutics-presents-data-on-rvu120-at-the-european-hematology-association-congress-2025

Ryvu Therapeutics Presents Data on RVU120 at the ... RVU120, when combined with venetoclax (VEN), shows promising anti-leukemic activity in patients with relapsed or refractory acute myeloid leukemia (r/r AML)

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04021368

NCT04021368 | RVU120 in Patients With Acute Myeloid ... This first-in-human study will evaluate RVU120 (SEL120), a novel small molecule CDK8/19 inhibitor, in patients with Acute Myeloid Leukemia (AML) or ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/6005/527602/River-52-A-Multicenter-Open-Label-Clinical-Trial

River-52: A Multicenter, Open-Label Clinical Trial of RVU120 ... RVU120 showed robust anti-cancer activity ... Treatment Patterns and Outcomes of Patients with Primary or Secondary Acute Myeloid Leukemia ...

4. ryvu.com ryvu.com/press-release/ryvu-therapeutics-announces-three-abstracts-on-romaciclib-rvu120-and-one-abstract-on-dapolsertib-men1703-at-the

News Romaciclib continues to show efficacy in AML: Data from the Phase II RIVER-81 trial suggest that romaciclib restores sensitivity to ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124088335

A Multicenter, Open-Label Clinical Trial of RVU120 in ... This trial is evaluating the clinical activity of RVU120 in participants with AML or HR-MDS who have failed at least one line of previous therapy.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06268574

NCT06268574 | Safety and Efficacy of RVU120 for ... The goal of this study is to assess the safety, tolerability, anti-tumor activity (efficacy), pharmacokinetics (PK), and pharmacodynamics (PD) of the agent RVU ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10428712/

A PHASE1B DOSE ESCALATION STUDY IN RELAPSE ... RVU120 is a novel CDK8/CDK19 kinase inhibitor currently under clinical investigation in a phase 1b dose escalation study for relapsed/refractory AML and high- ...