RVU120 for Acute Myeloid Leukemia

(RIVER-52 Trial)

Recruiting at 49 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

94 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this study is to assess the safety, tolerability, anti-tumor activity (efficacy), pharmacokinetics (PK), and pharmacodynamics (PD) of the agent RVU120 when administered to adult patients with relapsed or refractory acute myeloid leukemia (AML) or relapsed or progressing high-risk myelodysplastic syndrome (HR-MDS) and who have no alternative therapies available. The study consists of two parts. Part 1 will assess the safety and tolerability of the dosages given and the level of anti-tumor activity or clinical response. Based on the results from part 1 the study will continue to enrol patient into Part 2 which will continue to evaluate safety and tolerability and anti-tumor activity in a larger number of patients.

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.

What data supports the effectiveness of the drug RVU120 for treating Acute Myeloid Leukemia?

Selinexor, a component related to RVU120, has shown promising activity in treating relapsed or refractory acute myeloid leukemia (AML) in several studies. It demonstrated anti-leukemia effects both as a single agent and in combination with other treatments, with some patients achieving complete remission and improved survival rates. ^{1 2 3 4 5}

What makes the drug RVU120 unique for treating acute myeloid leukemia?

RVU120 is a novel treatment for acute myeloid leukemia that may offer a different mechanism of action compared to traditional chemotherapy, potentially targeting specific pathways involved in the disease. Unlike standard treatments, RVU120 could provide an alternative for patients who do not respond well to existing therapies. ^{4 6 7 8 9}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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 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]

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 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]

References

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

Selinexor in combination with decitabine in patients with acute myeloid leukemia: results from a phase 1 study. [2021]

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

A phase 1 clinical trial of single-agent selinexor in acute myeloid leukemia. [2021]

3. United States 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. [2022]

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

Phase 1 study of selinexor in combination with salvage chemotherapy in Adults with relapsed or refractory Acute myeloid leukemia. [2023]

5. England 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. [2022]

6. England 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. [2023]

7. India pubmed.ncbi.nlm.nih.gov

Clinical Characteristics and Prognosis of 167 Cases of Acute Erythroleukemia. [2020]

8. 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]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Retinoic acid and arsenic trioxide in the treatment of acute promyelocytic leukemia: current perspectives. [2022]