CPX-351 for Acute Myeloid Leukemia

Overseen By Sudipto Mukherjee, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Case Comprehensive Cancer Center

Disqualifiers: CNS involvement, Heart disease, Active malignancy, 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: Unknown

13 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate how effective lower doses of CPX-351 are in older participants with relapsed/refractory acute myeloid leukemia (AML) who are not eligible to receive intensive chemotherapy and in participants with myelodysplastic syndromes (MDS) after Hypomethylating Agents (HMA) failure.

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

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is CPX-351 (Vyxeos) generally safe for humans?

CPX-351 (Vyxeos) has a safety profile similar to standard chemotherapy for acute myeloid leukemia, with some patients experiencing prolonged low blood cell counts and infections like febrile neutropenia (fever with low white blood cells), pneumonia, and sepsis. It is important to note that patients with Wilson disease were excluded from studies due to concerns about elemental copper in the formulation. ^{1 2 3 4 5}

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

CPX-351 is unique because it combines two chemotherapy drugs, daunorubicin and cytarabine, in a special liposomal form that maintains a fixed 1:5 ratio, which enhances their effectiveness together. This formulation has been shown to improve survival rates and reduce early mortality compared to the traditional 7+3 chemotherapy regimen, especially in older adults with high-risk or secondary acute myeloid leukemia. ^{1 2 3 6 7}

Research Team

Sudipto Mukherjee, MD, PhD, MPH

Principal Investigator

Cleveland Clinic, Case Comprehensive Cancer Center

Eligibility Criteria

This trial is for older adults with relapsed/refractory acute myeloid leukemia (AML) who can't have intensive chemotherapy, or those with myelodysplastic syndromes (MDS) unresponsive to prior treatments. Participants should be in fairly good health otherwise, able to perform daily activities with minimal help (ECOG <=2), and have normal liver and kidney function.

Inclusion Criteria

Primary refractory or relapsed AML (defined by 2016 World Health Organization [WHO] criteria) patients who are not suitable for or not willing to receive intensive chemotherapy as evaluated by the treating physician. Primary refractory disease is defined as: Failure to achieve a CR, CRi, or mLFS (defined as <5% Bone Marrow (BM) blasts) after receiving 1 or 2 cycles of remission induction chemotherapy. Failure to achieve a CR, CRi, or MLFS (defined as <5% BM blasts) after receiving 4 cycles of non-intensive chemotherapy or whose disease progressed at any time point during the treatment. Participants with MDS (according to 2016 WHO criteria) who did not respond to treatment with azacitidine, decitabine, or combination of HMA with another drug or lost their response to initial therapy with HMA. Eastern Cooperative Oncology Group (ECOG) performance status <=2 Adequate hepatic (serum total bilirubin < 1.5 x ULN, Serum glutamic pyruvic transaminase (SGPT) and/or serum glutamate oxaloacetate transaminase (SGOT) <2.5 x ULN) and renal function (creatinine < 1.5mg/dL). Participants must be willing and able to review, understand, and provide written consent before starting therapy.

Exclusion Criteria

Active signs or symptoms of central nervous system (CNS) involvement by malignancy (lumbar puncture [LP] not required). Prior 7+3 remission induction chemotherapy for MDS or AML More than 2 lines of prior non-intensive therapy. New York Heart Association (NYHA) class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia on rhythm control strategy or on pacemaker, uncontrolled hypertension (blood pressure > 160 systolic and > 110 diastolic not responsive to antihypertensive medication) Acute myocardial infarction in the previous 12 weeks (from the start of treatment). Any serious medical condition, laboratory abnormality, or psychiatric illness that, in the view of the treating physician, would place the participant at an unacceptable risk if he or she were to participate in the study or would prevent that person from giving informed consent. Any active malignancy (unrelated, non-hematological malignancy) diagnosed within the past 6 months of starting the study drug (other than curatively treated carcinoma-in-situ of the cervix or non-melanoma skin cancer). History of allergic reactions attributed to compounds of similar chemical or biologic composition to CPX-351. Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Known history of HIV or active hepatitis B or C. No major surgery within 2 weeks prior to study enrollment. Pregnant or breast feeding Male and female participants who are fertile who do not agree to use an effective barrier methods of birth control (i.e. abstinence) to avoid pregnancy while receiving study treatment and for 30 days after last dose of study treatment. Non-childbearing is defined as > 1 year postmenopausal or surgically sterilized. Acute promyelocytic leukemia (APL)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive lower dose CPX-351 as induction therapy

6 months

Maintenance Treatment

Participants continue with lower dose CPX-351 as maintenance therapy

5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• CPX-351

Trial Overview The study tests lower doses of CPX-351 on participants to see how effective it is against AML and MDS when standard therapies fail. It's aimed at those who are older or cannot tolerate more aggressive treatment options.

Participant Groups

Group I: Primary refractory/relapsed AML Experimental Treatment 1 Intervention

Lower dose CPX-351 in participants with primary refractory/relapsed AML. Participants will receive an induction and maintenance phase of CPX-351

Group II: MDS after HMA failure Experimental Treatment 1 Intervention

Lower dose CPX-351 in participants with MDS after HMA failure. Participants will receive an induction and maintenance phase of CPX-351

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?

Case Comprehensive Cancer Center

Lead Sponsor

Trials

472

Recruited

33,400+

Findings from Research

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]

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]

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]

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 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]

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]

References

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. 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]

4. 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]

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

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

6. 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]

7. 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]