CPX-351 for Acute Myeloid Leukemia

Not currently recruiting at 3 trial locations

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Roswell Park Cancer Institute

Disqualifiers: CNS leukemia, Cardiovascular disease, HIV, 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 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new chemotherapy treatment called CPX-351 (Liposome-encapsulated Daunorubicin-Cytarabine) for individuals with a specific type of acute myeloid leukemia (AML). The goal is to evaluate the treatment's effectiveness in stopping cancer cell growth and spread. Participants receive the drug through an IV on specific days, with possible additional rounds if needed. Individuals newly diagnosed with certain types of AML who have not received prior AML treatment might be suitable for this study. As a Phase 2 trial, this study measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important research.

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

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team 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 treatment for secondary acute myeloid leukemia (sAML), is about as safe as standard chemotherapy. Studies indicate that CPX-351 does not cause more side effects than traditional treatments, allowing patients to generally tolerate it well.

For instance, one study found that CPX-351 has a similar safety level compared to the usual 7+3 chemotherapy regimen. Another study noted its effectiveness in both younger and older adults with sAML, suggesting it is a reliable treatment option.

While CPX-351 carries some risks, research supports its use as a safe and promising choice for treating leukemia. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard chemotherapy treatments for acute myeloid leukemia (AML), which typically involve separate infusions of daunorubicin and cytarabine, CPX-351 combines these two drugs into a single liposome-encapsulated formula. This unique delivery method allows both drugs to be released in a fixed, synergistic ratio directly into the bloodstream, potentially enhancing their effectiveness and reducing toxicity. Researchers are excited about CPX-351 because it may improve patient outcomes by offering a more efficient and potentially safer treatment option compared to traditional chemotherapy regimens.

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

Research has shown that CPX-351, the treatment under study in this trial, is an effective option for acute myeloid leukemia (AML), especially for patients with secondary AML (sAML). Studies have found that CPX-351 significantly extends patient survival compared to the traditional 7+3 chemotherapy treatment. In one study, CPX-351 doubled the five-year survival rate for patients with sAML. Real-world evidence also supports its effectiveness for both younger and older patients. This treatment combines two chemotherapy drugs, cytarabine and daunorubicin, in a special delivery system to better target cancer cells. ^{1 3 4 5 6}

Who Is on the Research Team?

Steven D. Green

Principal Investigator

Roswell Park Cancer Institute

Are You a Good Fit for This Trial?

This trial is for patients under 60 with secondary acute myeloid leukemia (AML) who haven't had AML treatment before. They must have good heart function, normal kidney and liver tests, and not be pregnant or breastfeeding. Participants need to use birth control and can't have severe diseases that could interfere with the study.

Inclusion Criteria

Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to enrollment and commit to two forms of birth control

Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

I have AML that developed after cancer treatment.

Exclusion Criteria

I have a liver condition like cirrhosis or hepatitis.

I have a history of Wilson disease or similar conditions.

I have been treated for acute myeloid leukemia before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3, and 5 in the absence of disease progression or unacceptable toxicity

1 week

Re-Induction

Patients who do not achieve remission receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3 in the absence of disease progression or unacceptable toxicity

1 week

Consolidation

Patients who achieve CR receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3. Treatment repeats every 45 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity

Up to 90 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Liposome-encapsulated Daunorubicin-Cytarabine

Trial Overview The trial is testing CPX-351, a chemo drug combo of daunorubicin-cytarabine in liposomes, designed to kill cancer cells or stop them from growing and spreading. It's for younger patients to see how well it works against secondary AML.

How Is the Trial Designed?

Group I: Treatment (CPX-351) Experimental Treatment 1 Intervention

INDUCTION: Patients receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3, and 5 in the absence of disease progression or unacceptable toxicity. RE-INDUCTION: Patients who do not achieve remission receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3 in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Beginning 5-8 weeks after the start of the last induction, patients who achieve CR receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3. Treatment repeats every 45 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

Liposome-encapsulated Daunorubicin-Cytarabine is already approved in United States for the following indications:

Approved in United States as Vyxeos for:

• Acute Myeloid Leukemia with myelodysplasia-related changes (AML-MRC)
• Therapy-related AML (t-AML)

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

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 liposome formulation of cytarabine and daunorubicin, demonstrated potent anti-leukemic activity in a mouse model, effectively reducing leukemia cells in bone marrow to undetectable levels for weeks, unlike the free-drug cocktail which only provided temporary suppression.

The enhanced efficacy of CPX-351 is attributed to its ability to deliver higher concentrations of the drugs directly to leukemia cells, leading to prolonged exposure and selective killing of these cells, while causing similar levels of myelosuppression as the free-drug cocktail.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leukemia-selective uptake and cytotoxicity of CPX-351, a synergistic fixed-ratio cytarabine:daunorubicin formulation, in bone marrow xenografts. Lim, WS., Tardi, PG., Dos Santos, N., et al.[2022]

CPX-351, a liposomal formulation of cytarabine and daunorubicin, showed high efficacy in treating childhood acute lymphoblastic leukemia (ALL) xenograft models, achieving complete responses in four B-lineage models and a partial response in one T-lineage model.

The drug was administered at a dose that resulted in plasma drug exposures similar to those seen in patients with acute myeloid leukemia (AML), indicating its potential effectiveness and safety for use in pediatric leukemia treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of CPX-351, (cytarabine:daunorubicin) liposome injection, against acute lymphoblastic leukemia (ALL) xenograft models of the Pediatric Preclinical Testing Program. Carol, H., Fan, MM., Harasym, TO., 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 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 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™, a liposomal formulation of daunorubicin and cytarabine, has been shown to significantly improve overall survival and event-free survival in older patients with newly diagnosed high-risk acute myeloid leukaemia (AML) compared to conventional chemotherapy (7+3).

The treatment also resulted in higher rates of complete remission and was well-tolerated, with a safety profile similar to that of the standard chemotherapy regimen, making it a valuable option for patients with therapy-related AML or AML with myelodysplasia-related changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daunorubicin/Cytarabine Liposome: A Review in Acute Myeloid Leukaemia. Blair, HA.[2020]

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]

CPX-351 (Vyxeos®) is a dual-drug liposomal formulation of cytarabine and daunorubicin designed to improve efficacy in treating acute myeloid leukemia (AML) by maintaining a synergistic 5:1 drug ratio, which enhances its effectiveness compared to traditional chemotherapy regimens.

The liposomal encapsulation allows for controlled release and preferential uptake by malignant cells, which helps to protect the drugs from metabolism and reduces exposure to off-target tissues, contributing to a favorable safety profile while effectively targeting leukemia cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CPX-351: a nanoscale liposomal co-formulation of daunorubicin and cytarabine with unique biodistribution and tumor cell uptake properties. Mayer, LD., Tardi, P., Louie, AC.[2020]

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 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. 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. 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.

3. 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.

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. 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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12063066/

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 ...