CPX-351 for Myeloid Cancer

Overseen By Raul C. Ribeiro, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: St. Jude Children's Research Hospital

Must not be taking: Investigational drugs, Heart failure meds

Disqualifiers: De novo AML, Trisomy 21, 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

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

Compensation: Varies

Number of Visits: 3

Duration: 6-8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the effects of an experimental drug, CPX-351, for patients with specific types of secondary myeloid cancer, a type of blood cancer. It targets those who developed cancer after treatments like chemotherapy or radiation. Suitable candidates are individuals who previously received treatments for other cancers and now face challenges with secondary myeloid conditions affecting their daily lives. The trial will assess CPX-351's effectiveness in helping these patients. If successful, it could lead to improved treatment options in the future. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to potential advancements in cancer care.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but there are restrictions on certain therapies. You may need to stop some treatments like myelosuppressive chemotherapy, certain biologic agents, and hematopoietic growth factors before starting the trial.

Is there any evidence suggesting that CPX-351 is likely to be safe for humans?

Research has shown that CPX-351 is safe, with studies finding its safety comparable to standard chemotherapy, allowing most patients to tolerate it well. Real-world evidence supports its safety for treating specific blood cancers, such as t-AML and AML-MRC. The FDA has approved CPX-351 for another condition, indicating it has passed safety tests for that use, which adds reassurance about its safety. Overall, based on research and real-world use, CPX-351 appears to be a safe option. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for myeloid cancer?

Unlike the standard chemotherapy options for myeloid cancers, CPX-351 is a unique formulation that combines two chemotherapy drugs, daunorubicin and cytarabine, in a specific 5:1 molar ratio. This ratio is delivered within a liposomal encapsulation, which helps target the cancer cells more effectively while potentially reducing toxicity to healthy cells. Researchers are excited about CPX-351 because this innovative delivery method could enhance the treatment’s effectiveness and safety compared to traditional chemotherapy regimens.

What evidence suggests that CPX-351 might be an effective treatment for myeloid cancer?

Research has shown that CPX-351, the investigational treatment in this trial, effectively treats certain types of acute myeloid leukemia (AML). It combines two drugs, cytarabine and daunorubicin, into tiny fat particles, enhancing their ability to target cancer cells. Studies have found that CPX-351 improves overall survival compared to traditional 7+3 chemotherapy, particularly in patients with high-risk or secondary AML. Real-world data supports its effectiveness and safety, demonstrating better outcomes for both younger and older patients. This evidence suggests that CPX-351 could be a promising option for treating secondary myeloid neoplasms. ^{2 3 4 6 7}

Who Is on the Research Team?

Raul C. Ribeiro, MD

Principal Investigator

St. Jude Children's Research Hospital

Marcin Wlodarski, MD, PhD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

This trial is for young people aged 1 to less than 22 with secondary myeloid neoplasms (SMNs). They must have certain organ functions within normal ranges, no severe prior treatment effects, and not be on conflicting medications. Those with specific genetic conditions or other types of leukemia are excluded.

Inclusion Criteria

I have been diagnosed with MDS/AML caused by previous cancer treatment.

I am between 1 and 21 years old.

My brain functions are mostly normal, with minor issues.

Exclusion Criteria

Patients who are currently receiving another investigational drug

Patients with known active HBV and HCV infections

I have been diagnosed with AML for the first time.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive up to 2 cycles of CPX-351 for remission induction

6-8 weeks

2 visits (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Long-term follow-up

Participants are monitored for overall survival and event-free survival

3 years

What Are the Treatments Tested in This Trial?

Interventions

• CPX-351

Trial Overview

The study tests CPX-351 (VYXEOS), a drug under investigation for treating SMNs. Participants may also undergo allogeneic hematopoietic stem cell transplantation if needed. The trial aims to understand the effectiveness and safety of CPX-351 in this patient group.

How Is the Trial Designed?

Group I: CPX-351 Experimental Treatment 3 Interventions

Participants will receive CPX-351 for remission induction, and then will proceed to allogeneic HSCT or other therapies as per institutional practice. Intrathecal (IT) chemotherapy will be given on Day 1 of each cycle, for all participants, but may be delayed if clinically indicated. IT cytarabine, IT methotrexate, and IT methotrexate/hydrocortisone/cytarabine (MHA) according to age are all acceptable.

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?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

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

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]

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]

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]

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 study of 195 patients treated with CPX-351 and 160 patients treated with the conventional 7+3 therapy, CPX-351 was associated with a significantly shorter hospital length of stay (LOS), averaging 183.7 days compared to 197.1 days for 7+3 (p<0.001).

Despite the shorter LOS with CPX-351, the use of supportive care, such as blood products and anti-infectives, was similar between the two treatment groups, indicating that CPX-351 may offer resource advantages without compromising care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Hospital Length of Stay and Supportive Care Utilization Between Patients Treated with CPX-351 and 7+3 for Therapy-Related Acute Myeloid Leukemia or Acute Myeloid Leukemia with Myelodysplasia-Related Changes. Price, K., Cao, Z., Lipkin, C., et al.[2022]

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]

Vyxeos (CPX-351) received FDA approval for treating adults with newly diagnosed therapy-related acute myeloid leukemia (t-AML) or acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), based on a study involving 309 patients aged 60-75 that showed improved overall survival (9.6 months vs. 5.9 months with standard treatment).

The safety profile of Vyxeos was comparable to the standard treatment, but it was associated with longer periods of neutropenia and thrombocytopenia, highlighting the need for careful monitoring and a warning against switching between different formulations of daunorubicin and cytarabine during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: (Daunorubicin and Cytarabine) Liposome for Injection for the Treatment of Adults with High-Risk Acute Myeloid Leukemia. Krauss, AC., Gao, X., Li, L., et al.[2020]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12185649/

The Role of CPX-351 in the Acute Myeloid Leukemia ...

CPX-351 is a chemotherapy treatment for acute myeloid leukemia (AML) that combines the two drugs cytarabine and daunorubicin in very small fat ...

2.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6520

V-RULES: Real-world effectiveness and safety of CPX-351 ...

These results highlight the effectiveness and safety of CPX-351 for the treatment of t-AML and AML-MRC in the US RW setting, consistent with the pivotal trial ...

3.

vyxeospro.com

vyxeospro.com/clinical-data/efficacy

The only choice for more than double the 5-year OS vs 7+3 1

VYXEOS is the only FDA-approved treatment for sAML demonstrating superior overall survival a in a Phase 3 study.

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S2152265023002124

Real-World Experience With CPX-351 Treatment for Acute ...

This study provides real-world survival outcomes data suggesting that CPX-351 is an effective treatment for both younger (<60 years) and older (≥60 years) ...

5.

thelancet.com

thelancet.com/journals/lanhae/article/PIIS2352-3026(21)00134-4/abstract

CPX-351 versus 7+3 cytarabine and daunorubicin ...

CPX-351: an attractive option for the treatment of older patients with high-risk or secondary acute myeloid leukaemia

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40348597/

The Clinical Safety and Efficacy of Cytarabine ...

This review presents strong evidence supporting CPX-351 as a therapeutic alternative with superior efficacy and comparable safety to standard chemotherapy ...

7.

bloodcancerunited.org

bloodcancerunited.org/resources/newsroom/publication-cpx-351-clinical-data-blood-advances-phase-3-post-hoc-analyses

Publication of CPX-351 Clinical Data in 'Blood Advances'

These results suggest deeper remissions may be achieved with CPX-351, leading to improved OS. LLS funded both Phase 2 and Phase 3 clinical development of Vyxeos ...