CPX-351 + Quizartinib for Acute Myeloid Leukemia

Overseen By Musa Yilmaz

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: CYP3A4 inducers, QT prolongers

Disqualifiers: Cardiovascular disease, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: 30

52 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take certain drugs that affect heart rhythm or strong CYP3A4 inducers. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug CPX-351 + Quizartinib for Acute Myeloid Leukemia?

Research shows that CPX-351, a combination of two drugs in a special delivery system, significantly improved survival in older adults with a specific type of acute myeloid leukemia compared to traditional chemotherapy. This suggests it could be an effective option for treating this condition. ^{1 2 3 4 5}

Is CPX-351 safe for humans?

CPX-351, also known as Vyxeos, has been shown to have a safety profile similar to traditional chemotherapy in studies with older adults with high-risk acute myeloid leukemia. It is generally considered to have an acceptable tolerability profile, meaning it is reasonably safe for use in humans. ^{1 2 5 6 7}

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

CPX-351 is unique because it combines two chemotherapy drugs, daunorubicin and cytarabine, in a special liposome (a tiny bubble-like structure) that helps deliver the drugs more effectively to cancer cells. This combination has shown improved survival rates compared to the traditional 7+3 chemotherapy regimen, especially in older adults with high-risk acute myeloid leukemia. ^{5 6 8 9 10}

What is the purpose of this trial?

This phase I/II trial studies the side effects and best dose of CPX-351 in combination with quizartinib for the treatment of acute myeloid leukemia and high risk myelodysplastic syndrome. CPX-351, composed of chemotherapy drugs daunorubicin and cytarabine, works 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. Quizartinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The goal of this study is to learn if the combination of CPX-351 and quizartinib can help to control acute myeloid leukemia and myelodysplastic syndrome.

Research Team

Musa Yilmaz

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with Acute Myeloid Leukemia (AML) or high-risk Myelodysplastic Syndrome (MDS), who have either not received chemotherapy or have had up to four prior treatments. Participants must be over 60 years old for the frontline cohort, and at least 18 for the relapsed/refractory cohort. They should have adequate organ function, no severe concurrent illnesses, and women of childbearing potential must use contraception.

Inclusion Criteria

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

I have been diagnosed with AML or high-risk MDS, not including APL.

I have AML or MDS and have had 1-4 treatments for it.

Exclusion Criteria

Sustained heart rate of < 50/minute on pre-entry ECG

I do not have major stomach or intestine problems that affect medication absorption.

Atrial fibrillation documented within 2 weeks prior to first dose of study drug

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive CPX-351 IV on days 1, 3, and 5 and quizartinib PO on days 6-19. Treatment repeats every 28 days for up to 2 cycles.

Up to 8 weeks

Multiple visits for IV administration and monitoring

Consolidation

Patients receive CPX-351 IV on days 1 and 3 and quizartinib PO on days 4-28. Treatment repeats every 28 days for 2 cycles.

8 weeks

Multiple visits for IV administration and monitoring

Maintenance

Patients receive quizartinib PO on days 1-28 in the absence of disease progression or unacceptable toxicity.

Variable, based on patient response

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Up to 5 years

Follow-up at 30 days, then every 3-6 months

Treatment Details

Interventions

• Liposome-encapsulated Daunorubicin-Cytarabine
• Quizartinib

Trial Overview The trial is testing CPX-351 (a combination of daunorubicin and cytarabine encapsulated in liposomes) alongside quizartinib to see if they can effectively control AML and MDS. It's a phase I/II study that aims to determine the best dose while monitoring side effects when these drugs are used together.

Participant Groups

Group I: Treatment (CPX-351, quizartinib) Experimental Treatment 2 Interventions

INDUCTION: Patients receive CPX-351 IV over 90 minutes on days 1, 3 and 5 and quizartinib PO on days 6-19. Patients who do not respond to treatment during cycle 1 receive CPX-351 IV on days 1 and 3 and quixartinib PO on days 6-19 during cycle 2. Treatment repeats every 28 days for up 2 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients receive CPX-351 over 90 minutes on days 1 and 3 and quizartinib PO on days 4-28 of cycle 1. Treatment with CPX-351 repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive quizartinib PO on days 1-28 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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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 (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]

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]

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 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 liposomal formulation of cytarabine and daunorubicin, shows superior cytotoxicity compared to standard daunorubicin and cytarabine combinations in cytarabine-resistant leukemia cells, indicating its potential effectiveness in treating high-risk acute myeloid leukemia (AML).

In primary AML patient samples, CPX-351 demonstrated a rapid increase in intracellular ara-CTP levels, particularly in patients who later experienced treatment failure, suggesting that Flu-CPX may improve patient outcomes by enhancing drug activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CPX-351 exhibits hENT-independent uptake and can be potentiated by fludarabine in leukaemic cells lines and primary refractory AML. Anderson, E., Mehta, P., Heywood, J., et al.[2022]

CPX-351, a liposomal formulation of daunorubicin and cytarabine, significantly improves overall survival in older adults (ages 60-75) with newly diagnosed high-risk or secondary acute myeloid leukemia (AML), showing a median survival of 9.56 months compared to 5.95 months with standard chemotherapy.

Preliminary evidence suggests that combining CPX-351 with FLT3 inhibitors may offer a promising treatment strategy for patients with FLT3 mutation-positive AML, which is associated with poorer outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CPX-351 in FLT3-mutated acute myeloid leukemia. Andrews, C., Pullarkat, V., Recher, C.[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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

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

2. New Zealand pubmed.ncbi.nlm.nih.gov

CPX-351: a nanoscale liposomal co-formulation of daunorubicin and cytarabine with unique biodistribution and tumor cell uptake properties. [2020]

3. United States 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. [2021]

4. 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]

5. 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]

6. 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]

7. England pubmed.ncbi.nlm.nih.gov

CPX-351 exhibits hENT-independent uptake and can be potentiated by fludarabine in leukaemic cells lines and primary refractory AML. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

CPX-351 in FLT3-mutated acute myeloid leukemia. [2023]

9. 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]

10. Netherlands pubmed.ncbi.nlm.nih.gov

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