CPX-351 + Gilteritinib for Acute Myeloid Leukemia

Recruiting at 183 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

Trial Summary

What is the purpose of this trial?

This phase III trial compares standard chemotherapy to therapy with liposome-encapsulated daunorubicin-cytarabine (CPX-351) and/or gilteritinib for patients with newly diagnosed acute myeloid leukemia with or without FLT3 mutations. Drugs used in chemotherapy, such as daunorubicin, cytarabine, and gemtuzumab ozogamicin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. CPX-351 is made up of daunorubicin and cytarabine and is made in a way that makes the drugs stay in the bone marrow longer and could be less likely to cause heart problems than traditional anthracycline drugs, a common class of chemotherapy drug. Some acute myeloid leukemia patients have an abnormality in the structure of a gene called FLT3. Genes are pieces of DNA (molecules that carry instructions for development, functioning, growth and reproduction) inside each cell that tell the cell what to do and when to grow and divide. FLT3 plays an important role in the normal making of blood cells. This gene can have permanent changes that cause it to function abnormally by making cancer cells grow. Gilteritinib may block the abnormal function of the FLT3 gene that makes cancer cells grow. The overall goals of this study are, 1) to compare the effects, good and/or bad, of CPX-351 with daunorubicin and cytarabine on people with newly diagnosed AML to find out which is better, 2) to study the effects, good and/or bad, of adding gilteritinib to AML therapy for patients with high amounts of FLT3/ITD or other FLT3 mutations and 3) to study changes in heart function during and after treatment for AML. Giving CPX-351 and/or gilteritinib with standard chemotherapy may work better in treating patients with acute myeloid leukemia compared to standard chemotherapy alone.

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.

What data supports the effectiveness of the drug CPX-351 for treating acute myeloid leukemia?

Research shows that CPX-351 significantly improves survival and remission rates in older adults with high-risk acute myeloid leukemia compared to traditional chemotherapy. It also has a similar safety profile and lower early mortality rates. ^{1 2 3 4 5}

Is CPX-351 safe for treating acute myeloid leukemia?

CPX-351, also known as Vyxeos, has been shown to have a safety profile comparable to conventional chemotherapy in older adults with acute myeloid leukemia. Common side effects include febrile neutropenia (fever with low white blood cell count), pneumonia, and sepsis, but early mortality rates were lower compared to standard treatment. ^{1 2 4 6 7}

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

CPX-351 is unique because it combines two drugs, daunorubicin and cytarabine, in a special liposomal form that helps them work better together, and it is specifically approved for certain types of acute myeloid leukemia (AML) that are therapy-related or have myelodysplasia-related changes. This drug has shown improved survival rates compared to the traditional 7+3 chemotherapy regimen, especially in older adults with high-risk AML. ^{1 2 3 7 8}

Research Team

Todd M Cooper

Principal Investigator

Children's Oncology Group

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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]

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 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]

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]

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. Netherlands pubmed.ncbi.nlm.nih.gov

Real-world experience with CPX-351 in high-risk acute myeloid leukemia. [2023]

4. United States 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. [2022]

5. Netherlands 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. [2020]

6. 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]

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

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

8. 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]