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

25 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to learn the effects of treatment with an investigational drug, CPX-351 in patients with secondary myeloid neoplasms (SMNs).

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.

What data supports the effectiveness of the drug CPX-351 for myeloid cancer?

Research shows that CPX-351 improves survival and remission rates in older adults with high-risk acute myeloid leukemia compared to traditional chemotherapy. Patients treated with CPX-351 had longer overall survival and better post-transplant outcomes. ^{1 2 3 4 5}

Is CPX-351 safe for humans?

CPX-351, also known as Vyxeos, has been shown to have a safety profile similar to standard chemotherapy treatments for acute myeloid leukemia (AML), with some differences like more prolonged low blood cell counts. It is generally considered safe for use in humans, but patients with Wilson disease were excluded from studies due to concerns about elemental copper in the formulation. ^{2 3 4 5 6}

What makes the drug CPX-351 unique for treating myeloid cancer?

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. This formulation improves survival rates and reduces early mortality compared to the traditional 7+3 chemotherapy regimen for older adults with high-risk acute myeloid leukemia. ^{1 2 3 5 7}

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 (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 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]

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]

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]

References

1. New Zealand 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. [2022]

2. 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]

3. 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]

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

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

5. Germany pubmed.ncbi.nlm.nih.gov

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

6. United States 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. [2020]

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]