CPX-351 + Gilteritinib for Acute Myeloid Leukemia

Recruiting at 222 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Children's Oncology Group

Must not be taking: CYP3A4 inducers, P-gp inducers

Disqualifiers: Fanconi anemia, Trisomy 21, Cardiac dysfunction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

1186 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to improve treatment for acute myeloid leukemia (AML) by testing a new drug combination. Researchers compare standard chemotherapy with a new treatment using CPX-351, a special form of chemotherapy, and gilteritinib, which targets specific gene changes in leukemia cells. Individuals newly diagnosed with AML and possessing certain genetic features in their cancer may be suitable for this study. This trial is for those who have not received other cancer treatments and have specific genetic markers linked to AML. As a Phase 3 trial, it represents the final step before potential FDA approval, offering participants a chance to contribute to groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are taking strong inducers of CYP3A4 or P-glycoprotein, you may need to avoid them if you receive gilteritinib during the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that CPX-351 has a safety profile similar to traditional chemotherapy for treating acute myeloid leukemia (AML). Patients often tolerate it well, with side effects comparable to standard treatments. The FDA has approved CPX-351 for some types of AML, indicating its safety.

Research involving 319 patients with relapsed or refractory AML showed that gilteritinib was generally well-tolerated, with manageable side effects. The FDA has also approved gilteritinib for certain AML cases, suggesting its safety for human use.

Both treatments have undergone testing in various settings, and substantial research supports their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because CPX-351 and Gilteritinib Fumarate offer unique advantages for treating acute myeloid leukemia (AML). Unlike traditional chemotherapy, CPX-351 is a liposomal formulation, which means it delivers drugs directly into cancer cells more efficiently, potentially reducing side effects. Gilteritinib Fumarate targets specific mutations in cancer cells, particularly FLT3 mutations, which are present in many AML patients and associated with poor prognosis. Together, these treatments could offer a more targeted approach, improving outcomes for patients who have limited options with existing therapies.

What evidence suggests that this trial's treatments could be effective for acute myeloid leukemia?

Research has shown that CPX-351, a combination of daunorubicin and cytarabine, significantly improves survival rates for individuals with acute myeloid leukemia (AML). Studies indicate it more than doubles the 5-year survival rate compared to standard chemotherapy for older adults with high-risk AML. In this trial, some participants will receive CPX-351. Meanwhile, gilteritinib, another treatment option in this trial, targets patients with a specific genetic change called the FLT3 mutation in AML. This drug demonstrated promising results, with an average survival time of 11 months and notable survival rates at 1 and 3 years. Both treatments are effective, each addressing different aspects of AML. ^{1 3 6 7 8}

Who Is on the Research Team?

Todd M Cooper

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for patients under 22 years old newly diagnosed with acute myeloid leukemia (AML), either with or without FLT3 gene mutations. They must have certain levels of cancer cells in their blood or bone marrow and agree to use contraception if of reproductive potential. Excluded are those with specific genetic syndromes, prior significant cancer treatments, pregnant or breastfeeding women, and those not using effective contraception.

Inclusion Criteria

I am at least 5 years old.

I have been recently diagnosed with a type of leukemia called AML.

All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria

I am currently pregnant.

I do not have a genetic heart rhythm disorder or congenital heart block.

I have been diagnosed with Shwachman Diamond syndrome.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction 1

Patients receive initial chemotherapy treatment with various drugs including cytarabine, daunorubicin, and gemtuzumab ozogamicin, with or without gilteritinib, depending on the arm and risk group.

4-6 weeks

Multiple visits for chemotherapy administration

Induction 2

Continuation of chemotherapy treatment with adjustments based on CNS status and risk group, including additional drugs like CPX-351 and gilteritinib.

4-6 weeks

Multiple visits for chemotherapy administration

Intensification

Patients receive high-dose chemotherapy to further reduce leukemia cells, with drugs such as high-dose cytarabine and etoposide, and possibly gilteritinib.

4-6 weeks per cycle

Multiple visits for chemotherapy administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments for minimal residual disease and cardiac function.

Up to 3 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• CPX-351
• Gilteritinib Fumarate

Trial Overview

The study compares standard chemotherapy against therapy combining CPX-351 (liposome-encapsulated daunorubicin-cytarabine) and/or gilteritinib in AML patients. It aims to see if these new therapies are more effective or cause fewer heart problems than traditional treatments, especially for those with FLT3 mutations.

How Is the Trial Designed?

Group I: Arm BD Low Risk Group 2 Experimental Treatment 18 Interventions

Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)

Group II: Arm BD High Risk Group Experimental Treatment 16 Interventions

Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)

Group III: Arm BC Low Risk Group 2 Experimental Treatment 18 Interventions

Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)

Group IV: Arm BC High Risk Group Experimental Treatment 16 Interventions

Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)

Group V: Arm B Low Risk Group 2 Experimental Treatment 15 Interventions

Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)

Group VI: Arm B Low Risk Group 1 Experimental Treatment 15 Interventions

Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)

Group VII: Arm B High Risk Group Experimental Treatment 15 Interventions

Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)

Group VIII: Arm AD Low Risk Group 2 Experimental Treatment 18 Interventions

Arm AD Low Risk Group 2: See Detailed Description.

Group IX: Arm AD High Risk Group Experimental Treatment 17 Interventions

Arm AD High Risk Group: See Detailed Description.

Group X: Arm AC Low Risk Group 2 Experimental Treatment 18 Interventions

Arm AC Low Risk Group 2: See Detailed Description.

Group XI: Arm AC High Risk Group Experimental Treatment 17 Interventions

Arm AC High Risk Group: See Detailed Description.

Group XII: Arm A Low Risk Group 2 Experimental Treatment 17 Interventions

Arm A Low Risk Group 2: See Detailed Description.

Group XIII: Arm A Low Risk Group 1 Experimental Treatment 16 Interventions

Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)

Group XIV: Arm A High Risk Group Experimental Treatment 16 Interventions

Arm A High Risk Group: See Detailed Description.

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?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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]

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]

In a phase III trial involving 309 patients aged 60 to 75 with newly diagnosed high-risk secondary acute myeloid leukemia (sAML), CPX-351 significantly improved median overall survival compared to the standard 7+3 chemotherapy regimen, with a median survival of 9.56 months versus 5.95 months.

The overall remission rate was also higher with CPX-351 (47.7%) compared to 7+3 (33.3%), while the safety profile was comparable between the two treatments, indicating that CPX-351 is both more effective and similarly safe for older adults with sAML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemia. Lancet, JE., Uy, GL., Cortes, JE., et al.[2022]

The introduction of CPX-351, a liposomal formulation of daunorubicin and cytarabine, has significantly improved overall survival in patients aged 60-75 with newly diagnosed secondary and therapy-related acute myeloid leukemia (AML) compared to the traditional '7 + 3' regimen.

CPX-351 received FDA approval in August 2017, marking a significant advancement in AML treatment after decades of stagnation in therapy options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daunorubicin-cytarabine liposome (CPX-351) in the management of newly diagnosed secondary AML: A new twist on an old cocktail. Maakaron, JE., Mims, AS.[2020]

CPX-351, a combination of daunorubicin and cytarabine, has been shown to improve survival and remission rates in adults with newly diagnosed therapy-related acute myeloid leukemia (AML) compared to standard chemotherapy, with comparable safety profiles.

Real-world studies have expanded the understanding of CPX-351's effectiveness in diverse patient populations, including younger adults and those with specific genetic mutations, helping healthcare providers make better-informed treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with CPX-351 in high-risk acute myeloid leukemia. Lemoli, RM., Montesinos, P., Jain, A.[2023]

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]

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]

Citations

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pmc.ncbi.nlm.nih.gov

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

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

These protective effects and confirmed effectiveness in everyday practice mean CPX-351 is a safe and effective treatment option for people with ...

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vyxeospro.com

vyxeospro.com/clinical-data/efficacy

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

Outcomes by number of induction cycles with CPX-351 vs 7+3 chemotherapy in older adults with newly diagnosed high-risk/secondary acute myeloid leukemia (sAML).

3.

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) ...

4.

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.

5.

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 ...

6.

vyxeospro.com

vyxeospro.com/

VYXEOS® | A Treatment for sAML

... acute myeloid leukemia. Safety. The safety profile of VYXEOS in the Phase 3 study was comparable with 7+3, with similar types and severity of adverse reactions.

7.

clinical-lymphoma-myeloma-leukemia.com

clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(19)30843-2/fulltext

Pooled Clinical Safety Analysis of CPX-351 Versus ...

Across studies comprising the CPX-351 clinical development program, CPX-351 demonstrated a safety profile comparable to conventional chemotherapy in adults with ...

8.

aetna.com

aetna.com/cpb/medical/data/900_999/0921.html

Daunorubicin-Cytarabine Liposome (Vyxeos)

U.S. Food and Drug Administration (FDA)-Approved Indications. Vyxeos is indicated for the treatment of newly-diagnosed therapy-related acute myeloid leukemia (t ...