18 Participants Needed

Vyxeos + Gemtuzumab Ozogamicin for Acute Myeloid Leukemia

JE
LN
Overseen ByLisa Nardelli
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

The purpose of the study is to determine the safety of combining the drugs gemtuzumab ozogamicin (GO) with CPX-351 in order to treat the disease, as well as to find the maximum tolerated dose level and recommended Phase 2 dose level of GO with a fixed dose of CPX-351.

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.

What data supports the effectiveness of the drug Vyxeos + Gemtuzumab Ozogamicin for Acute Myeloid Leukemia?

Gemtuzumab ozogamicin, when combined with daunorubicin and cytarabine, showed improved event-free survival in patients with newly diagnosed acute myeloid leukemia (AML), while Vyxeos, a combination of daunorubicin and cytarabine in a liposomal form, demonstrated a significant improvement in overall survival compared to standard chemotherapy in high-risk AML patients.12345

Is Vyxeos + Gemtuzumab Ozogamicin safe for humans?

Vyxeos and Gemtuzumab Ozogamicin have been studied for safety in humans, showing some common side effects like prolonged low blood cell counts, infections, and liver issues. Serious side effects include bleeding and liver disease, but these treatments have been approved for use in certain types of leukemia, indicating a favorable balance between benefits and risks.45678

What makes the drug Vyxeos + Gemtuzumab Ozogamicin unique for treating acute myeloid leukemia?

This drug combination is unique because it targets the CD33 antigen on leukemia cells using Gemtuzumab Ozogamicin, a monoclonal antibody linked to a powerful toxin, and combines it with Vyxeos, a liposomal formulation of two chemotherapy drugs, daunorubicin and cytarabine, which work together to enhance the treatment's effectiveness.910111213

Research Team

Onyee Chan | Moffitt

Onyee Chan, MD

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

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.
See 10 more

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
See 12 more

Timeline

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

Treatment Details

Interventions

  • Gemtuzumab Ozogamicin
  • Vyxeos
Trial OverviewThe 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.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Dose EscalationExperimental Treatment2 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)

Find a Clinic Near You

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 profile image

Bruce C. Cozadd

Jazz Pharmaceuticals

Chief Executive Officer since 2009

BA in Economics from Yale University, MBA from Stanford University

Dr. Austin profile image

Dr. Austin

Jazz Pharmaceuticals

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Findings from Research

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

References

Long-term disease-free survival after gemtuzumab, intermediate-dose cytarabine, and mitoxantrone in patients with CD33(+) primary resistant or relapsed acute myeloid leukemia. [2019]
Reformulating acute myeloid leukemia: liposomal cytarabine and daunorubicin (CPX-351) as an emerging therapy for secondary AML. [2020]
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]
FDA Approval: Gemtuzumab Ozogamicin for the Treatment of Adults with Newly Diagnosed CD33-Positive Acute Myeloid Leukemia. [2019]
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. [2022]
Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. [2020]
The EMA Review of Mylotarg (Gemtuzumab Ozogamicin) for the Treatment of Acute Myeloid Leukemia. [2020]
FDA Approval Summary: (Daunorubicin and Cytarabine) Liposome for Injection for the Treatment of Adults with High-Risk Acute Myeloid Leukemia. [2020]
Trials with gemtuzumab ozogamicin (Mylotarg) combined with chemotherapy regimens in acute myeloid leukemia. [2019]
10.United Statespubmed.ncbi.nlm.nih.gov
Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia. [2022]
Gemtuzumab ozogamicin: a review of its use in acute myeloid leukaemia. [2022]
Gemtuzumab ozogamicin in non-acute promyelocytic acute myeloid leukemia. [2019]
13.United Statespubmed.ncbi.nlm.nih.gov
Acute Left Ventricular Dysfunction Following Gemtuzumab Ozogamicin in Two Pediatric AML Patients. [2023]