Vyxeos + Gemtuzumab Ozogamicin for Acute Myeloid Leukemia

Overseen By Lisa Nardelli

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Investigational drugs

Disqualifiers: APL, CNS leukemia, Severe liver disease, others

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

Compensation: Varies

Number of Visits: Unknown

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on testing a new treatment combination for individuals with newly diagnosed acute myeloid leukemia (AML). The aim is to determine the safety and optimal dose levels of combining two drugs: Vyxeos, a chemotherapy drug, and gemtuzumab ozogamicin (Mylotarg), an antibody-drug conjugate. The trial examines how these drugs can work together to combat the disease. Individuals with AML who have specific characteristics, such as CD33-positive myeloblasts, and who have not yet received certain treatments for AML, may be suitable candidates for this trial. As a Phase 1 trial, the research seeks to understand how the treatment functions in participants, offering them the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does allow the use of hydroxyurea until the first day of study treatment. If you are on other medications, it's best to discuss with the study team to see if they are compatible with the trial.

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

Research has provided some information about the safety of using Vyxeos and gemtuzumab ozogamicin (GO) together to treat acute myeloid leukemia. Previous studies tested this combination and found that patients can tolerate it, though side effects may occur.

Vyxeos contains cytarabine and daunorubicin and has proven effective in treating older adults, though it can cause common side effects like low blood cell counts. GO targets specific cancer cells but can also lead to side effects such as liver issues and low blood cell counts.

When combined, studies have shown that patients can tolerate the treatment, but monitoring for side effects is crucial. The research aims to determine the right dose that is both effective and safe.

Overall, while the combination appears promising, the study remains in the early stages to better understand its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Vyxeos combined with Gemtuzumab Ozogamicin for treating acute myeloid leukemia because this combination has the potential to bring new hope to patients. Unlike traditional chemotherapy drugs, Vyxeos is a liposomal formulation of two chemotherapy agents, which helps deliver the drugs more directly to the cancer cells, potentially increasing effectiveness and reducing side effects. Gemtuzumab Ozogamicin, on the other hand, is an antibody-drug conjugate that specifically targets cancer cells by binding to a protein called CD33, which is commonly found on leukemia cells. This targeted approach can lead to more precise treatment, sparing healthy cells and potentially improving outcomes for patients.

What evidence suggests that Vyxeos + Gemtuzumab Ozogamicin could be effective for acute myeloid leukemia?

This trial will explore the combination of Vyxeos (CPX-351) with gemtuzumab ozogamicin for treating acute myeloid leukemia (AML). Research shows that this combination may be effective, as earlier studies have indicated benefits for some patients whose AML had returned or was resistant to previous treatments. This combination has been linked to longer survival compared to standard treatments, particularly in older adults with newly diagnosed secondary AML. Vyxeos, which includes two chemotherapy drugs, has demonstrated better results, such as increasing the chances of stem cell transplants. Early evidence suggests that adding gemtuzumab ozogamicin might enhance these benefits. Participants in this trial will undergo dose escalation to determine the maximum tolerated dose of this combination. ^{2 3 5 6 7}

Who Is on the Research Team?

Onyee Chan, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

Adults aged 18-70 with newly diagnosed AML that's not high-risk, who can undergo intensive chemo and have CD33-expressing myeloblasts. They must be willing to use effective contraception, have no severe liver disease or heart failure, and cannot be pregnant or breastfeeding. Prior treatment for non-AML conditions is okay if it was over two weeks ago.

Inclusion Criteria

I am willing and able to follow all study rules and attend all appointments.

My organs are functioning well.

I can use hydroxyurea for cytoreduction until my study treatment starts.

Exclusion Criteria

My AML is classified as high-risk according to ELN 2017.

I have an active hepatitis B or C infection.

Treatment with another investigational drug within 14 days

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Dose escalation to determine the maximum tolerated dose (MTD) of CPX-351 in combination with Gemtuzumab Ozogamicin in participants with newly diagnosed acute myeloid leukemia.

Up to 18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Gemtuzumab Ozogamicin
• Vyxeos

Trial Overview The trial tests combining Vyxeos (CPX-351) with Gemtuzumab Ozogamicin for treating AML. It aims to find the safest dose of GO when used with a fixed dose of CPX-351 and determine how well patients tolerate this combination therapy.

How Is the Trial Designed?

Group I: Dose Escalation Experimental Treatment 2 Interventions

Dose escalation to determine the maximum tolerated dose (MTD) of CPX-351 in combination with Gemtuzumab Ozogamicin in participants with newly diagnosed acute myeloid leukemia. Participants will be treated in cohorts of size three to six and the dosage will be escalated if the clinical toxicity is acceptable. A total of 3 dose levels will be used.

Gemtuzumab Ozogamicin is already approved in United States, European Union for the following indications:

Approved in United States as Mylotarg for:

• Acute myeloid leukemia (AML)

Approved in European Union as Mylotarg for:

• Acute myeloid leukemia (AML)

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

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

The combination treatment of gemtuzumab ozogamicin, intermediate-dose cytarabine, and mitoxantrone (MIDAM) resulted in a 63% overall response rate in 62 patients with refractory or relapsed CD33(+) acute myeloid leukemia, with 50% achieving complete remission.

While the MIDAM regimen showed promising efficacy, it also had safety concerns, including a 16% rate of severe hyperbilirubinemia and four early toxic deaths, highlighting the need for further randomized trials to establish its safety and effectiveness as a standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term disease-free survival after gemtuzumab, intermediate-dose cytarabine, and mitoxantrone in patients with CD33(+) primary resistant or relapsed acute myeloid leukemia. Chevallier, P., Delaunay, J., Turlure, P., et al.[2019]

CPX-351, a liposomal-encapsulated combination of daunorubicin and cytarabine, has been approved for treating therapy-related acute myeloid leukemia (tAML) and AML with myelodysplasia-related changes (AML-MRCs), showing improved overall survival and remission rates in older patients compared to the traditional '7 + 3' treatment.

In a Phase III trial involving patients aged 60-75, CPX-351 demonstrated higher rates of complete remission and event-free survival, suggesting that its fixed 5:1 drug ratio may enhance efficacy in these challenging subgroups of AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reformulating acute myeloid leukemia: liposomal cytarabine and daunorubicin (CPX-351) as an emerging therapy for secondary AML. Chen, EC., Fathi, AT., Brunner, AM.[2020]

Vyxeos, a liposomal formulation combining daunorubicin and cytarabine, significantly improves overall survival in patients aged 60-75 with untreated high-risk acute myeloid leukemia (AML), showing a median survival of 9.56 months compared to 5.95 months with standard chemotherapy.

The study demonstrated that Vyxeos not only enhances survival rates but also increases the likelihood of patients undergoing hematopoietic stem cell transplantation, which is crucial for potentially curing AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EMA Review of Daunorubicin and Cytarabine Encapsulated in Liposomes (Vyxeos, CPX-351) for the Treatment of Adults with Newly Diagnosed, Therapy-Related Acute Myeloid Leukemia or Acute Myeloid Leukemia with Myelodysplasia-Related Changes. Tzogani, K., Penttilä, K., Lapveteläinen, T., et al.[2022]

Gemtuzumab ozogamicin (Mylotarg) is being studied in ongoing trials for its safety and efficacy in treating acute myeloid leukemia (AML) patients, both newly diagnosed and those with relapsed or refractory disease.

While gemtuzumab ozogamicin shows an acceptable toxicity profile as a standalone treatment, there is a notable risk of veno-occlusive disease when used in combination with chemotherapy, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trials with gemtuzumab ozogamicin (Mylotarg) combined with chemotherapy regimens in acute myeloid leukemia. Stadtmauer, EA.[2019]

Gemtuzumab ozogamicin (GO) has shown moderate effectiveness as a single agent in treating acute myeloid leukemia (AML), but it demonstrates promising results when combined with intensive chemotherapy, particularly in patients with relapsed AML defined by specific genetic mutations.

Recent Phase III trials did not show overall survival benefits for GO in newly diagnosed AML, but there is potential for improved outcomes in genetically defined subgroups, highlighting the importance of personalized therapy in AML treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemtuzumab ozogamicin in non-acute promyelocytic acute myeloid leukemia. Hütter, ML., Schlenk, RF.[2019]

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]

Gemtuzumab ozogamicin is an effective treatment for older patients (≥60 years) with CD33-positive acute myeloid leukaemia (AML) in first relapse, achieving complete remission in about 25% of cases.

While it has a tolerability profile that is generally acceptable, serious side effects like hepatotoxicity can occur, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemtuzumab ozogamicin: a review of its use in acute myeloid leukaemia. Fenton, C., Perry, CM.[2022]

In the phase III ALFA-0701 trial involving 271 adults aged 50-70 with de novo acute myeloid leukemia (AML), the addition of a reduced dose of gemtuzumab ozogamicin to standard chemotherapy significantly improved event-free survival (EFS) by 34% compared to chemotherapy alone.

While overall survival (OS) favored the gemtuzumab ozogamicin group, it was not statistically significant, and the main safety concern was prolonged thrombocytopenia, with some cases of veno-occlusive disease observed, indicating a favorable benefit/risk ratio for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Lambert, J., Pautas, C., Terré, C., et al.[2020]

Gemtuzumab ozogamicin, when combined with daunorubicin and cytarabine, significantly improved event-free survival in adults with newly diagnosed CD33-positive acute myeloid leukemia (AML), with a median EFS of 13.6 months compared to 8.8 months for the standard treatment alone.

As a monotherapy, gemtuzumab ozogamicin also showed improved overall survival (4.9 months) compared to best supportive care (3.6 months), although serious side effects like hemorrhage and prolonged thrombocytopenia were more common with the combination treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval: Gemtuzumab Ozogamicin for the Treatment of Adults with Newly Diagnosed CD33-Positive Acute Myeloid Leukemia. Jen, EY., Ko, CW., Lee, JE., et al.[2019]

Gemtuzumab ozogamicin (GO) is effective in treating pediatric patients with relapsed/refractory acute myeloid leukemia, as demonstrated by the two cases where patients achieved remission after treatment.

Despite its efficacy, GO can lead to severe acute left ventricular dysfunction, highlighting the need for monitoring cardiac function during treatment, although both patients recovered with medical therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Left Ventricular Dysfunction Following Gemtuzumab Ozogamicin in Two Pediatric AML Patients. McNerney, KO., Oranges, K., Seif, AE., et al.[2023]

Gemtuzumab ozogamicin (Mylotarg) has been approved for treating acute myeloid leukemia (AML) in patients aged 15 and older, showing significant improvements in event-free survival and reduced relapse risk based on a meta-analysis of 3,325 patients.

While Mylotarg is effective, it is associated with common side effects such as hemorrhage and infection, particularly when used in combination with other chemotherapy drugs like daunorubicin and cytarabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The EMA Review of Mylotarg (Gemtuzumab Ozogamicin) for the Treatment of Acute Myeloid Leukemia. Ali, S., Dunmore, HM., Karres, D., et al.[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]

Gemtuzumab ozogamicin is an effective treatment for patients with CD33 positive acute myeloid leukemia (AML) in first relapse, showing an overall response rate of 30% in Phase 2 trials involving 142 patients, with a complete response rate of 16%.

While it offers a potentially better tolerability profile compared to conventional chemotherapy, it carries risks of significant side effects, including myelosuppression, hepatotoxicity, and severe allergic reactions, necessitating careful patient monitoring and management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia. Bross, PF., Beitz, J., Chen, G., et al.[2022]

Citations

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Liposomal Cytarabine and Daunorubicin (CPX-351) in ... INTRODUCTION: The outcome of patients (pts) with R/R AML or MDS after failing HMA and/or BCL-2 inhibitor combinations is poor. CPX-351 (Vyxeos™) is a dual ...

2. ashpublications.org ashpublications.org/blood/article/134/Supplement_1/2642/423255/Liposomal-Cytarabine-and-Daunorubicin-CPX-351-in

Liposomal Cytarabine and Daunorubicin (CPX-351) in ... INTRODUCTION: The outcome of patients (pts) with relapsed or refractory AML (R/R AML) or MDS after failing hypomethylating agents (HMA) is poor.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7485353/

EMA Review of Daunorubicin and Cytarabine ... Secondary endpoints support the primary outcome, in particular an increased rate of hematopoietic stem cell transplantation, which is potentially the only ...

4. tandfonline.com tandfonline.com/doi/full/10.1080/10428194.2024.2438809

CPX-351 plus gemtuzumab ozogamicin for relapsed ... In this multicenter phase Ib trial, we investigated the combination of CPX-351 and gemtuzumab ozogamicin (GO) in relapsed/refractory acute myeloid leukemia (AML) ...

5. 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.

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/2903/533109/Combination-of-CPX-351-and-Gemtuzumab-Ozogamicin

Combination of CPX-351 and Gemtuzumab Ozogamicin (GO ... We present the updated results of the single-arm pilot study (NCT03672539) of CPX351- GO combination therapy in pts with CD33 positive R/R AML ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03878927?term=Cholesterol%20AND%20blast&viewType=Table&checkSpell=&rank=3

CPX-351+GO in Subjects 55 Years Old, or Older, With AML ... This is an open label study to assess the safety and efficacy of CPX-351 in combination with gemtuzumab ozogamicin (GO) as first intensive therapy in older ...