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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and assess the effects of combining CPX-351, which contains the chemotherapy drugs daunorubicin and cytarabine, with quizartinib for treating acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). CPX-351 kills cancer cells or stops their growth, while quizartinib (also known as Vanflyta) blocks enzymes that aid tumor cell growth. The trial seeks participants with AML or high-risk MDS who have either never undergone chemotherapy or have tried other treatments but still require assistance. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this combination therapy.

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.

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

Research has shown that CPX-351, when combined with treatments like venetoclax or midostaurin, generally has a manageable safety profile. Most patients can tolerate the side effects, which are usually mild. CPX-351, composed of daunorubicin and cytarabine, has proven safer and more effective than standard chemotherapy for some patients.

Quizartinib blocks enzymes that promote cancer cell growth. While specific safety data for its use with CPX-351 is limited, ongoing studies aim to determine if the combination is well-tolerated. As this trial is in its early stages, researchers focus on understanding side effects and determining optimal dosages. They continue to gather data to ensure the combination's safety for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CPX-351 combined with quizartinib for treating Acute Myeloid Leukemia because this combo targets the cancer in a novel way. CPX-351 is a unique formulation that encapsulates two chemotherapy drugs, daunorubicin and cytarabine, into liposomes, which may enhance drug delivery directly to cancer cells while potentially reducing side effects. Meanwhile, quizartinib is a targeted therapy that specifically inhibits FLT3, a protein often mutated in leukemia cells, which can help in controlling aggressive forms of the disease. This dual approach of combining a targeted inhibitor with an enhanced chemotherapy delivery system could offer more effective treatment outcomes compared to traditional chemotherapy alone.

What evidence suggests that the combination of CPX-351 and quizartinib could be effective for acute myeloid leukemia?

Research has shown that CPX-351, a treatment combining two drugs inside a tiny fat bubble, helps people with acute myeloid leukemia (AML) live longer than with traditional chemotherapy. In this trial, participants will receive a combination of CPX-351 and quizartinib. Studies have found that quizartinib improves survival by blocking certain enzymes that cancer cells need to grow. Together, these treatments aim to be more effective against AML by preventing cancer cells from multiplying and spreading. Early results suggest that this combination could be a promising option for managing AML. ^{6 7 8 9 10}

Who Is on the Research Team?

Musa Yilmaz

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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.

I have not had any major surgery in the last 14 days.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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]

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]

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, 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]

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 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 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]

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]

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 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]

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 ...

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. clinicaltrials.gov clinicaltrials.gov/study/NCT04128748

Study Details | NCT04128748 | Liposomal Cytarabine and ... 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.

7. ashpublications.org ashpublications.org/bloodneoplasia/article/2/4/100123/537598/V-FAST-a-phase-1b-master-trial-to-investigate-CPX

V-FAST: a phase 1b master trial to investigate CPX-351 ... CPX-351 combined with venetoclax or midostaurin demonstrated a manageable safety profile and promising remission rates. These results support further ...

8. 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 ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10691756/

CPX-351 in FLT3-mutated acute myeloid leukemia - PMC Phase III trial data have shown CPX-351 to be significantly more effective than standard-of-care 7 + 3 chemotherapy (7 days cytarabine; 3 days ...

10. sciencedirect.com sciencedirect.com/science/article/pii/S2950328025000585

V-FAST: a phase 1b master trial to investigate CPX-351 ... CPX-351 combined with venetoclax or midostaurin demonstrated a manageable safety profile and promising remission rates. •. These results support further ...