CPX-351 + Glasdegib for Acute Myeloid Leukemia

Not currently recruiting at 4 trial locations

Overseen By Chao Family Comprehensive Cancer Center University of California, Irvine

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, Irvine

Must not be taking: Glasdegib, CPX-351, Cytarabine, Daunorubicin

Disqualifiers: Neurologic disorder, HIV, Hepatitis, 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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with acute myeloid leukemia (AML), particularly those whose AML developed from earlier blood disorders or previous cancer treatments. The trial combines two drugs, CPX-351 (a chemotherapy drug) and Glasdegib (a hedgehog pathway inhibitor), to assess their effectiveness together in treating this type of leukemia. It suits individuals who have not received treatment for AML before but developed it from conditions like myelodysplastic syndrome, a bone marrow disorder that can progress to leukemia. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, certain treatments like leukapheresis, corticosteroids, and hydroxyurea are allowed for managing high white blood cell counts. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that the combination of CPX-351 and Glasdegib is likely to be safe for humans?

Research has shown that CPX-351 is generally easier for patients to handle compared to standard chemotherapy. One study found it to have a similar safety level, although 69% of patients experienced serious non-blood-related side effects during treatment. Despite this, the treatment appears promising and could be a good option for some people.

Glasdegib, an FDA-approved drug for certain types of leukemia, has a well-understood safety profile for those conditions. The combination of CPX-351 and Glasdegib is currently under study, but both drugs have demonstrated safety individually. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CPX-351 combined with Glasdegib for treating Acute Myeloid Leukemia (AML) because it brings a fresh approach compared to traditional therapies like anthracycline and cytarabine. CPX-351 is a liposomal formulation that delivers a fixed-dose combination of two chemotherapy drugs, potentially enhancing their effectiveness and reducing toxicity. Glasdegib, on the other hand, inhibits the Hedgehog signaling pathway, which can be involved in cancer cell survival, offering a novel mechanism that targets cancer cells in a unique way. This combination could improve outcomes for patients who might not respond well to standard treatments.

What evidence suggests that CPX-351 and Glasdegib could be effective for acute myeloid leukemia?

Research has shown that CPX-351 effectively treats certain types of acute myeloid leukemia (AML), outperforming traditional chemotherapy, particularly in older adults with high-risk AML. CPX-351 has been associated with longer survival and better outcomes in real-world situations.

In this trial, participants will receive a combination of CPX-351 and Glasdegib. While CPX-351 has strong evidence of effectiveness, results for Glasdegib have been mixed. When combined with standard treatments like azacitidine, Glasdegib has shown some promise, with patients living about 9 months on average. However, adding Glasdegib to other chemotherapy options did not significantly improve survival in previous trials. ^{6 7 8 9 10}

Who Is on the Research Team?

Deepa Jeyakumar

Principal Investigator

Chao Family Comprehensive Cancer Center

Are You a Good Fit for This Trial?

Adults over 18 with newly diagnosed, untreated Acute Myelogenous Leukemia (AML) that's related to prior therapy or myelodysplastic syndromes. Participants must have good heart function and organ health, not be pregnant or breastfeeding, agree to use birth control, and cannot have certain heart conditions, uncontrolled infections, other active cancers requiring treatment, or a history of severe medical disorders.

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.

I am a woman who could potentially become pregnant.

AST, ALT and alkaline phosphatase < 3 times the upper limit of normal, unless considered due to leukemic involvement

Exclusion Criteria

Baseline QT corrected interval based on Fridericia's formula (QTcF) interval > 450 ms

I have had a heart attack or severe heart issue in the last year.

I am HIV positive.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Subjects receive CPX-351 and Glasdegib with specific dosing schedules

4 weeks

Multiple visits for IV administration and monitoring

Re-induction (if needed)

Subjects receive adjusted doses of CPX-351 and Glasdegib

4 weeks

Multiple visits for IV administration and monitoring

Consolidation

Subjects receive lower doses of CPX-351 and Glasdegib

4 weeks

Multiple visits for IV administration and monitoring

Maintenance

Subjects receive Glasdegib daily for up to one year

Up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CPX-351
• Glasdegib

Trial Overview The trial is testing the effectiveness of combining two drugs: CPX-351 (a chemotherapy drug) and Glasdegib (a targeted therapy), in treating AML. It's an open-label study where all participants receive the same treatment without a comparison group.

How Is the Trial Designed?

Group I: CPX-351 and Glasdegib Experimental Treatment 2 Interventions

In Induction, subjects receive 44mg/m2/100mg/m2 IV on days 1, 3 and 5 and Glasdegib 100mg PO daily on days 6 to 28. If re-induction is needed: Subjects receive 44mg/m2/100mg/m2 IV on days 1 and 3 and Glasdegib 100mg PO daily on days 4 to 28. In consolidation: Subjects receive 29mg/m2/65mg/m2 IV on days 1 and 3 and Glasdegib 100mg PO daily on days 4 to 28. If maintenance is required, Subjects receive Glasdegib 100mg PO daily for up to one year

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?

University of California, Irvine

Lead Sponsor

Trials

580

Recruited

4,943,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

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

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]

Vyxeos (CPX-351) received FDA approval for treating adults with newly diagnosed therapy-related acute myeloid leukemia (t-AML) or acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), based on a study involving 309 patients aged 60-75 that showed improved overall survival (9.6 months vs. 5.9 months with standard treatment).

The safety profile of Vyxeos was comparable to the standard treatment, but it was associated with longer periods of neutropenia and thrombocytopenia, highlighting the need for careful monitoring and a warning against switching between different formulations of daunorubicin and cytarabine during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: (Daunorubicin and Cytarabine) Liposome for Injection for the Treatment of Adults with High-Risk Acute Myeloid Leukemia. Krauss, AC., Gao, X., Li, L., et al.[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]

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 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]

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]

Citations

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

The Role of CPX-351 in the Acute Myeloid Leukemia ... The important clinical trial that led to the approval of CPX-351 showed that CPX-351 works better than traditional chemotherapy for patients ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6520

V-RULES: Real-world effectiveness and safety of CPX-351 ... These results highlight the effectiveness and safety of CPX-351 for the treatment of t-AML and AML-MRC in the US RW setting, consistent with the pivotal trial ...

3. 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).

4. ashpublications.org ashpublications.org/bloodadvances/article/9/4/752/525800/Long-term-real-world-evidence-of-CPX-351-of-high

Long-term real-world evidence of CPX-351 of high-risk ... Long-term real-world evidence of CPX-351 of high-risk patients with AML identified high rate of negative MRD and prolonged OS.

5. 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) ...

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 ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.7510

Five-year final results of a phase III study of CPX-351 ... After 5 y of follow-up, improved OS was maintained in this phase 3 study, supporting that CPX-351 has the ability to produce or contribute to long-term ...

8. nature.com nature.com/articles/s41408-021-00558-5

Real-world experience of CPX-351 as first-line treatment ... With 69% of patients developing grade III/IV non-hematologic toxicity following induction and a day 30-mortality of 8% the safety profile was ...

9. tandfonline.com tandfonline.com/doi/full/10.1080/10428194.2019.1660970

Full article: CPX-351 (vyxeos) in AML CPX-351 is a liposomal formulation of cytarabine and daunorubicin encapsulated at a preclinically identified optimally synergistic 5:1 ratio.

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11450557/

Phase II Trial of CPX-351 in Patients with Acute Myeloid ... CPX-351 at 75 units/m2 has favorable safety and efficacy for AML patients at high risk of induction mortality with some tolerating the standard dose of 100 ...