CPX-351 for Acute Myeloid Leukemia

Recruiting at 3 trial locations

Overseen By Nicole Swanson

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Georgetown University

Disqualifiers: Uncontrolled heart disease, Hepatitis, CNS leukemia, 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: 6

Duration: 24 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called CPX-351 for individuals with acute myeloid leukemia (AML) who are in remission but cannot undergo a bone marrow transplant. Researchers aim to identify the most effective and safe dose of CPX-351, administered through an IV, to help maintain remission. The trial tests different dosing schedules to determine which is most effective with the fewest side effects. It is suitable for those who recently achieved complete remission after AML treatment and cannot have a bone marrow transplant due to health issues or personal preference. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

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

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

Research has shown that CPX-351, a combination of two chemotherapy drugs, is generally well-tolerated by patients. Studies have found that it can extend the lives of patients with acute myeloid leukemia (AML) compared to traditional treatments. In past research, CPX-351 was tested on both younger and older adults, showing promising results without unexpected side effects.

Some patients might experience common chemotherapy side effects like nausea or tiredness, but these are usually manageable. Since CPX-351 is being tested in phase 1 and 2 trials, it has passed initial safety checks, but researchers are still determining the safest dose. Overall, evidence suggests that CPX-351 is a promising treatment option with a safety profile similar to other chemotherapy drugs. ^{1 2 3 4 5}

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

Researchers are excited about CPX-351 for treating Acute Myeloid Leukemia (AML) because it offers a novel approach compared to traditional chemotherapy. CPX-351 is a unique liposomal formulation that combines two chemotherapy drugs, cytarabine and daunorubicin, in a fixed ratio, which is designed to optimize their therapeutic effects. This delivery method aims to enhance the drugs' effectiveness while potentially reducing toxicity. Unlike standard treatments that often require a combination of separate chemotherapy drugs, CPX-351's combined approach has the potential to improve outcomes for patients with AML.

What evidence suggests that CPX-351 could be an effective treatment for Acute Myeloid Leukemia?

Research has shown that CPX-351, the investigational treatment in this trial, effectively treats acute myeloid leukemia (AML), particularly in older adults with secondary AML (sAML). Studies have found that patients treated with CPX-351 live significantly longer than those receiving the traditional 7+3 chemotherapy. CPX-351 combines two drugs, cytarabine and daunorubicin, in tiny fat bubbles, enhancing its effectiveness against leukemia cells. In some studies, it more than doubled the five-year survival rate compared to standard treatments. These findings suggest that CPX-351 could be a strong option for treating AML. ^{2 4 6 7 8}

Who Is on the Research Team?

Kimberley Doucette, MD

Principal Investigator

Georgetown University

Are You a Good Fit for This Trial?

Adults over 18 with newly diagnosed Acute Myeloid Leukemia (AML) who are in complete remission, have undergone certain treatments up to a year, and can't have an allogeneic bone marrow transplant. Participants must be able to start treatment within 3 months of their last remission, have good heart function and organ health, and agree to use effective birth control.

Inclusion Criteria

I am either not able to have children or I use effective birth control methods.

My kidneys work well enough, with a creatinine clearance rate of 30 ml/min or more.

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

Exclusion Criteria

I have a heart condition that is not well-managed.

I have an active hepatitis B or C infection.

Erythema multiforme, toxic epidermal necrolysis, or Stevens-Johnson syndrome

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CPX-351 as maintenance therapy for 6 cycles, with dose adjustments based on toxicity

24 weeks

6 visits (in-person, every 28 days)

Follow-up

Participants are monitored for relapse-free survival and event-free survival for 1 year after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• CPX-351

Trial Overview The trial is testing CPX-351 for preventing AML relapse. It involves a dose de-escalation design where patients receive maintenance doses on specific days across six cycles. The safest maximum dose determined will be used in the phase II part of the study.

How Is the Trial Designed?

Group I: CPX-351 Experimental Treatment 1 Intervention

Dose Level 1: CPX-351 administered through intravenou infusion on Day 1 and Day 3 of 28 day cycle for 6 cycles or Dose Level -1: CPX-351 administered through intravenous infusion on Day 1 of each 28 day cycle for 6 cycles.

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?

Georgetown University

Lead Sponsor

Trials

355

Recruited

142,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

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, 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]

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 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 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]

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 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]

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 bubbles called ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2017.77.6112

CPX-351 (cytarabine and daunorubicin) Liposome for ... CPX-351 treatment is associated with significantly longer survival compared with conventional 7+3 in older adults with newly diagnosed sAML.

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. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/5922/505830/Real-World-Outcomes-of-CPX-351-Compared-to

Real World Outcomes of CPX-351 Compared to Traditional ... Here we present a real-world comparison of the efficacy and safety of patients with sAML receiving CPX-351 versus traditional 7+3 with HiDAC consolidation.

5. 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 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30024784/

CPX-351 (cytarabine and daunorubicin) Liposome for ... Prior clinical studies demonstrated a sustained drug ratio and exposure in vivo and prolonged survival versus standard-of-care cytarabine plus ...

7. 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) ...

8. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1111%2Fbjh.19622

British Journal of Haematology CPX-351 for acute myeloid leukaemia: real world results are comparable to trial outcomes and exceeds them in non-adverse risk patients—a ...