CPX-351 for Myelodysplastic Syndrome

Recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must not be taking: Hypomethylators, Lenalidomide

Disqualifiers: Active infection, Heart failure, Angina, Arrhythmia, Copper disorder, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 3 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This is a pilot and feasibility study of transplant eligible, higher risk myelodysplastic syndrome (MDS) patients to determine the safety and tolerability of a lower -dose and higher-dose CPX-351 regimen, with secondary objectives including complete remission (CR) rates and proportion of patients proceeding to transplant.

Do I need to stop my current medications for the CPX-351 trial?

The trial protocol does not specify if you need to stop your current medications. However, if you are on disease-modifying therapy for MDS or investigational agents, you cannot participate in the trial.

Is CPX-351 generally safe for humans?

CPX-351, also known as Vyxeos, has been studied in patients with acute myeloid leukemia (AML) and has shown a safety profile comparable to traditional chemotherapy, with some common side effects including febrile neutropenia (fever with low white blood cell count), pneumonia, and sepsis. It has been approved by the FDA and EMA for certain types of AML, indicating it is considered safe for use in humans for these conditions. ^{1 2 3 4 5}

How is the drug CPX-351 different from other treatments for myelodysplastic syndrome?

CPX-351 is unique because it combines two chemotherapy drugs, daunorubicin and cytarabine, in a special liposomal form that allows them to work together more effectively and stay in the body longer, potentially improving outcomes compared to traditional chemotherapy. ^{1 2 3 6 7}

What data supports the effectiveness of the drug CPX-351 for treating myelodysplastic syndrome?

CPX-351, a drug used for certain types of acute myeloid leukemia (AML), has shown to improve survival and remission rates compared to traditional chemotherapy in older adults with high-risk AML. This suggests it may also be effective for related conditions like myelodysplastic syndrome, as it uses a similar combination of drugs in a special formulation that enhances their effectiveness. ^{1 2 3 5 7}

Who Is on the Research Team?

Meagan Jacoby, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 with higher risk Myelodysplastic Syndrome (MDS) who are eligible for a transplant. They must have good kidney, liver, and heart function, an ECOG performance status ≤2, and no history of Wilson's disease or certain viral infections. Women must not be pregnant and participants should agree to use contraception.

Inclusion Criteria

My MDS is rated Intermediate to Very High with more than 5% myeloblasts in my bone marrow.

Total bilirubin ≤ 2.0 x IULN

AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN

Exclusion Criteria

I have a history of Wilson's disease or a similar copper-metabolism disorder.

I do not have an active HIV, HBV (unless from vaccine), or HCV (if treated) infection.

I have allergies to drugs similar to CPX-351 or others used in this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CPX-351 via IV infusion on Days 1, 3, and 5 of the first induction. A second induction may be considered based on bone marrow biopsy results.

3 weeks

3 visits (in-person) for first induction, additional visits if second induction is needed

Consolidation

In the absence of disease progression or unacceptable toxicity, patients may continue to consolidation or proceed to alloHCT.

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments for event-free survival, relapse-free survival, and overall survival.

5 years

What Are the Treatments Tested in This Trial?

Interventions

• CPX-351

Trial Overview The study tests two doses of CPX-351 (Vyxeos™) in MDS patients to see which is safer and more tolerable. It also looks at how many achieve complete remission and can proceed to a bone marrow transplant after treatment.

How Is the Trial Designed?

Group I: CPX-351 Experimental Treatment 4 Interventions

* CPX-351 will be given according to the assigned dose level over a minimum of a 90-minutes via IV infusion on Days 1, 3, and 5 of the first induction * If the treating physician elects to perform a day 14 bone marrow biopsy then, a second induction may be considered for patients in the absence of a chemoablated, hypocellular marrow on the Day 14 bone marrow assessment, if the patient has failed to achieve a marrow CR, and it is deemed safe to administer by the treating physician. The second induction uses a modified schedule in which CPX-351 will be given according to the assigned dose level on Days 1 and 3 * In the absence of disease progression or unacceptable toxicity, the patient may continue to consolidation at the discretion of the treating physician or the patient may proceed to alloHCT after induction at the discretion of the treating physician

CPX-351 is already approved in United States, European Union for the following indications:

Approved in United States as VYXEOS for:

• Newly-diagnosed therapy-related acute myeloid leukemia (t-AML)
• AML with myelodysplasia-related changes (AML-MRC)

Approved in European Union as VYXEOS for:

• Newly-diagnosed therapy-related acute myeloid leukemia (t-AML)
• AML with myelodysplasia-related changes (AML-MRC)

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Jazz Pharmaceuticals

Industry Sponsor

Trials

252

Recruited

35,100+

Bruce C. Cozadd

Jazz Pharmaceuticals

Chief Executive Officer since 2009

BA in Economics from Yale University, MBA from Stanford University

Dr. Austin

Jazz Pharmaceuticals

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Published Research Related to This Trial

In a phase 3 study involving 309 patients aged 60 to 75 with high-risk acute myeloid leukemia, CPX-351 significantly improved median overall survival compared to conventional 7+3 chemotherapy, while maintaining a similar safety profile.

The Quality-adjusted Time Without Symptoms of disease or Toxicity (Q-TWiST) analysis showed that CPX-351 provided a relative gain of 53.6% in quality-adjusted survival compared to 7+3, indicating a substantial clinical benefit for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality-adjusted Time Without Symptoms of disease or Toxicity (Q-TWiST) analysis of CPX-351 versus 7 + 3 in older adults with newly diagnosed high-risk/secondary AML. Cortes, JE., Lin, TL., Uy, GL., et al.[2021]

In a phase 3 study, CPX-351 significantly improved remission rates and overall survival in older adults with high-risk acute myeloid leukemia (AML) compared to the standard treatment (7+3), with higher remission frequencies of 41% versus 26% for adverse-risk patients.

The safety profile of CPX-351 was consistent with the overall study population, showing lower early mortality and shorter hospital stays, indicating it is a safe and effective treatment option for patients with adverse or intermediate-risk AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of CPX-351 versus 7 + 3 chemotherapy by European LeukemiaNet 2017 risk subgroups in older adults with newly diagnosed, high-risk/secondary AML: post hoc analysis of a randomized, phase 3 trial. Cortes, JE., Lin, TL., Asubonteng, K., et al.[2023]

CPX-351, a liposomal formulation of cytarabine and daunorubicin, shows prolonged exposure to these drugs in patients with relapsed and refractory acute myeloid leukemia (AML) without increasing non-hematologic toxicity, suggesting a safer treatment option.

The pharmacokinetic analysis of 39 patients indicates that the liposomal formulation allows for a significant reduction in drug clearance compared to non-encapsulated versions, which may lead to improved treatment outcomes and simplified regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Persistent cytarabine and daunorubicin exposure after administration of novel liposomal formulation CPX-351: population pharmacokinetic assessment. Nikanjam, M., Capparelli, EV., Lancet, JE., et al.[2020]

CPX-351 (vyxeos) is the first FDA-approved treatment specifically for adults with newly diagnosed acute myeloid leukemia (AML) with myelodysplasia-related changes or therapy-related AML, representing a significant advancement in targeted therapy for this subgroup.

In a phase III study involving patients aged 60-75, CPX-351 demonstrated a higher median overall survival (9.56 months) compared to the traditional 7+3 regimen (5.95 months), indicating its superior efficacy in treating this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CPX-351 (vyxeos) in AML. Alfayez, M., Kantarjian, H., Kadia, T., et al.[2021]

CPX-351, a liposomal formulation of cytarabine and daunorubicin, shows improved safety and efficacy in treating acute myeloid leukemia by providing prolonged tissue exposure and altered distribution compared to traditional non-liposomal combinations.

Preclinical studies indicate that CPX-351 maintains similar drug release and metabolism patterns as the standard treatment but results in lower unbound plasma concentrations, which may contribute to its enhanced therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, drug metabolism, and tissue distribution of CPX-351 in animals. Wang, Q., Tardi, P., Sadowski, N., et al.[2021]

In a phase II trial involving 56 patients with acute myeloid leukemia (AML), CPX-351 showed improved efficacy at higher doses, with a composite complete remission rate of 44% at 100 units/m2 compared to 19% at 50 units/m2.

The median overall survival was also better at higher doses, with 8.6 months for 75 units/m2 and 6.2 months for 100 units/m2, indicating that CPX-351 at 75 units/m2 is a promising treatment option for high-risk AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of CPX-351 in patients with acute myeloid leukemia at high risk for induction mortality. Issa, GC., Kantarjian, HM., Xiao, L., et al.[2023]

In a phase 3 trial involving 309 patients aged 60-75 with high-risk acute myeloid leukaemia, CPX-351 demonstrated a median overall survival of 9.33 months compared to 5.95 months for standard chemotherapy (7+3), indicating a significant improvement in survival rates.

After 5 years, the overall survival rate was 18% for the CPX-351 group versus 8% for the 7+3 group, suggesting that CPX-351 may lead to long-term remission and better outcomes for patients with this type of leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet, JE., Uy, GL., Newell, LF., et al.[2021]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Quality-adjusted Time Without Symptoms of disease or Toxicity (Q-TWiST) analysis of CPX-351 versus 7 + 3 in older adults with newly diagnosed high-risk/secondary AML. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of CPX-351 versus 7 + 3 chemotherapy by European LeukemiaNet 2017 risk subgroups in older adults with newly diagnosed, high-risk/secondary AML: post hoc analysis of a randomized, phase 3 trial. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Persistent cytarabine and daunorubicin exposure after administration of novel liposomal formulation CPX-351: population pharmacokinetic assessment. [2020]

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

CPX-351 (vyxeos) in AML. [2021]

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

Pharmacokinetics, drug metabolism, and tissue distribution of CPX-351 in animals. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Phase II trial of CPX-351 in patients with acute myeloid leukemia at high risk for induction mortality. [2023]

7. England pubmed.ncbi.nlm.nih.gov

CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. [2021]