AUTX-703 for Acute Myeloid Leukemia and Myelodysplastic Syndrome

Recruiting at 8 trial locations

Overseen By Auron Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Auron Therapeutics, Inc.

Must not be taking: CYP3A4 inhibitors, P-gp inhibitors

Disqualifiers: Active infection, Other malignancy, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

69 Participants Needed

Trial Summary

What is the purpose of this trial?

This Phase 1, multicenter, open-label, dose escalation and dose optimization study is designed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of AUTX-703 administered orally in subjects with advanced hematologic malignancies.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as strong CYP3A4 inhibitors or inducers, and P-gp and BCRP inhibitors or inducers, at least 14 days before starting the study treatment. If you are taking proton pump inhibitors, you should switch to another acid-reducing agent like an antacid or H2 blocker.

Is CPX-351 safe for treating acute myeloid leukemia and myelodysplastic syndrome?

CPX-351, a combination of daunorubicin and cytarabine in a liposomal form, has been approved by the FDA for treating certain types of acute myeloid leukemia (AML) and has shown improved survival rates compared to traditional treatments. While the articles do not provide specific safety data, the approval suggests it has been evaluated for safety in humans. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults over 18 with advanced blood cancers like AML or MDS that haven't responded to, can't handle, or have refused standard treatments. It's also open to those who've relapsed after a stem cell transplant. Participants need to be in fair health (ECOG ≤2), with good liver, kidney, and heart function, and a WBC count ≤20 × 10⁹/L.

Inclusion Criteria

R/R AML and has not achieved adequate response to, cannot tolerate, or refused all approved therapies known to be active for treatment of their disease OR R/R MDS with over 10% blasts in the bone marrow and has not achieved an adequate response to at least 4 cycles of a hypomethylating agent (HMA)- containing regimen or other treatment known to be active for their disease OR R/R AML or R/R MDS that has relapsed after a hematopoietic stem cell transplant (HSCT)

I can take care of myself but might not be able to do heavy physical work.

My liver is functioning well.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating dosages of AUTX-703 to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D)

Varies

Weekly visits

Dose Optimization

Participants receive AUTX-703 at selected dosages to further evaluate safety, PK, PD, and efficacy

Varies

Weekly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• AUTX-703

Trial Overview The study tests AUTX-703 taken orally by patients with certain blood cancers. It aims to find out how safe it is, what the body does with it (PK), how it affects the body (PD), and if it shows any signs of working against the cancer.

Participant Groups

Group I: Dose Optimization - Part B, Dosage 2 Experimental Treatment 1 Intervention

Participants will receive AUTX-703 at the second selected dosage determined from Part A, administered orally in tablet form either once, twice or three times weekly to further evaluate safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity at this specified dose.

Group II: Dose Optimization - Part B, Dosage 1 Experimental Treatment 1 Intervention

Participants will receive AUTX-703 at the first selected dosage determined from Part A, administered orally in tablet form either once, twice or three times weekly to further evaluate safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity at this specified dose.

Group III: Dose Escalation - Part A Experimental Treatment 1 Intervention

Participants will receive escalating dosages of AUTX-703 orally in tablet form once, twice or three times weekly to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D).

Who Is Running the Clinical Trial?

Auron Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

70+

Findings from Research

CPX-351, a new liposomal formulation of daunorubicin and cytarabine, has been approved for treating newly diagnosed therapy-related acute myeloid leukemia (tAML) and AML with myelodysplasia-related changes, showing improved overall survival compared to the traditional '7+3' regimen.

This new treatment delivers a fixed 5:1 ratio of the two drugs, which may enhance efficacy, particularly in older patients who typically have poorer outcomes with standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CPX-351 daunorubicin-cytarabine liposome: a novel formulation to treat patients with newly diagnosed secondary acute myeloid leukemia. Cafaro, A., Giannini, MB., Silimbani, P., et al.[2020]

The introduction of CPX-351, a liposomal formulation of daunorubicin and cytarabine, has significantly improved overall survival in patients aged 60-75 with newly diagnosed secondary and therapy-related acute myeloid leukemia (AML) compared to the traditional '7 + 3' regimen.

CPX-351 received FDA approval in August 2017, marking a significant advancement in AML treatment after decades of stagnation in therapy options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daunorubicin-cytarabine liposome (CPX-351) in the management of newly diagnosed secondary AML: A new twist on an old cocktail. Maakaron, JE., Mims, AS.[2020]

In 2017, the FDA approved five new drugs for treating acute myeloid leukemia (AML), including targeted therapies for specific genetic mutations (FLT3 and IDH2) and a new formulation of cytarabine-daunorubicin for certain types of AML.

The combination of the BCL-2 inhibitor venetoclax with low-intensity therapy showed promising results for older patients who are not suitable for intensive chemotherapy, indicating a shift towards more tailored treatment options in AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Midostaurin, enasidenib, CPX-351, gemtuzumab ozogamicin, and venetoclax bring new hope to AML. Wei, AH., Tiong, IS.[2022]

References

1. Italy pubmed.ncbi.nlm.nih.gov

CPX-351 daunorubicin-cytarabine liposome: a novel formulation to treat patients with newly diagnosed secondary acute myeloid leukemia. [2020]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Daunorubicin-cytarabine liposome (CPX-351) in the management of newly diagnosed secondary AML: A new twist on an old cocktail. [2020]

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

Current Status of CPX-351 Therapy in Acute Myeloid Leukemia and Myelodysplastic Syndrome. [2022]

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

Targeted therapy in acute myeloid leukaemia: current status and future directions. [2019]

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

Midostaurin, enasidenib, CPX-351, gemtuzumab ozogamicin, and venetoclax bring new hope to AML. [2022]