Vyxeos + Gilteritinib for Acute Myeloid Leukemia

Overseen by Onyee Chan, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Investigational agents

Disqualifiers: CNS involvement, GI abnormalities, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial combines Vyxeos, a chemotherapy drug, and Gilteritinib, a targeted therapy, for patients with a specific type of acute myeloid leukemia. Vyxeos attacks cancer cells using a combination of drugs, while Gilteritinib blocks a protein that helps these cancer cells grow. The goal is to see if this combination can help patients who have not responded to other treatments.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on other investigational drugs. If you are using hydroxyurea to control white blood cell counts, you can continue it until the study treatment starts.

What data supports the effectiveness of the drug combination Vyxeos and Gilteritinib for treating Acute Myeloid Leukemia?

Gilteritinib has shown effectiveness in treating patients with a specific type of Acute Myeloid Leukemia (AML) that has a mutation in the FLT3 gene, leading to higher response rates and longer survival compared to standard chemotherapy. Vyxeos, a combination of daunorubicin and cytarabine, has been effective in improving survival and remission rates in older adults with high-risk AML, making it a promising option when combined with Gilteritinib for treating AML. ^{1 2 3 4 5}

Is the combination of Vyxeos and Gilteritinib safe for treating acute myeloid leukemia?

Gilteritinib has been associated with side effects like anemia, fever, and low platelet counts, but these are generally manageable with dose adjustments. Vyxeos has a similar safety profile to standard chemotherapy, with common side effects including rash, fever, and fatigue. Both treatments have been used safely in adults with acute myeloid leukemia, but patients should be monitored for specific adverse effects. ^{3 6 7 8 9}

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

Vyxeos is a unique drug because it combines two chemotherapy agents, daunorubicin and cytarabine, in a special liposomal formulation 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 for certain high-risk types of acute myeloid leukemia. ^{2 3 7 9 10}

Research Team

Onyee Chan, MD

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

This trial is for adults with a specific mutation in their leukemia cells (FLT3) who have seen their disease return or not respond to treatment. They must be able to perform daily activities with some limitations, take oral meds, and use effective birth control if applicable. People can't join if they've had certain complications like severe graft versus host disease after a stem cell transplant or AML progression on gilteritinib.

Inclusion Criteria

Provision of signed and dated informed consent form

I had a stem cell transplant and my graft-versus-host disease is under control.

Breastfeeding mothers must agree to discontinue nursing

Exclusion Criteria

My digestive system can properly absorb medications.

Patients may not be receiving any other investigational agents

My body cannot handle the usual strong cancer drugs.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Participants receive Vyxeos on days 1, 3, and 5, and Gilteritinib on days 6-19

3 weeks

Consolidation Therapy

Participants in complete remission proceed to consolidation therapy with Vyxeos and Gilteritinib

Variable, based on remission status

Maintenance Therapy

Participants not proceeding to stem cell transplant enter maintenance phase with daily Gilteritinib

Up to 18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

• Gilteritinib (Tyrosine Kinase Inhibitor)
• Vyxeos (Chemotherapy)

Trial Overview The study tests combining Vyxeos (chemotherapy) and Gilteritinib (targeted therapy) in patients whose acute myeloid leukemia has returned or resisted treatment. It involves initial intense therapy followed by maintenance using Gilteritinib alone for those ineligible for stem cell transplant.

Participant Groups

Group I: Dose Expansion Arm Experimental Treatment 2 Interventions

Participants will receive intravenous Vyxeos on days 1, 3 and 5 and Gilteritinib will be given on days 6-19 of induction therapy in the dose determined in the dose escalation arm.

Group II: Dose Escalation Arm Experimental Treatment 2 Interventions

Participants will receive intravenous Vyxeos on days 1, 3 and 5 and Gilteritinib will be given on days 6-19 of induction therapy. The induction and reinduction dose of Vyxeos is 44mg/m2 daunorubicin and 100mg/m2 of cytarabine with each infusion. Dose level 1: Vyxeos + 120 mg Gilertinib In the event of a dose-limiting toxicity (DLT) at the initial dose level, a dose level minus (-) 1 is permitted Dose Level -1: Vyxeos + 80 mg Gilertinib

Gilteritinib is already approved in Japan for the following indications:

Approved in Japan as Xospata for:

• Acute myeloid leukemia (AML) with FLT3 mutation

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Patrick Hwu

H. Lee Moffitt Cancer Center and Research Institute

Chief Executive Officer since 2020

MD from The Medical College of Pennsylvania

Wade J. Sexton

H. Lee Moffitt Cancer Center and Research Institute

Chief Medical Officer

MD

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

Findings from Research

Gilteritinib fumarate is a highly selective oral FLT3 inhibitor that has shown significant efficacy in treating relapsed or refractory FLT3-mutated acute myeloid leukemia (AML), with clinical trials indicating higher response rates and longer overall survival compared to traditional salvage chemotherapy.

The drug was well tolerated in clinical trials, with dose-proportional plasma concentrations observed at doses ranging from 20 to 450 mg/day, supporting its safety profile for patients in Japan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacological and clinical profile of gilteritinib (Xospata® tablets 40 mg), a therapeutic agent for relapsed or refractory FLT3-mutated acute myeloid leukemia]. Mori, M., Hidaka, K.[2021]

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]

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, 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]

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]

Gilteritinib significantly improves overall survival and response rates in adults with relapsed or refractory acute myeloid leukaemia (AML) with FLT3 mutations, as demonstrated in the phase III ADMIRAL trial.

While gilteritinib is effective, it can cause serious side effects like anaemia and febrile neutropenia, but these are generally manageable with dose adjustments, highlighting the importance of monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gilteritinib: A Review in Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukaemia. Kang, C., Blair, HA.[2021]

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]

Gilteritinib has been approved in the EU as a monotherapy for adult patients with relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation, showing a significant improvement in overall survival (9.3 months) compared to salvage chemotherapy (5.6 months) in a phase III study with 371 participants.

The safety profile of gilteritinib is considered manageable, with common side effects including increases in liver enzymes and creatine phosphokinase, as well as gastrointestinal and general symptoms like fatigue and nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency Review of Gilteritinib (Xospata) for the Treatment of Adult Patients with Relapsed or Refractory Acute Myeloid Leukemia with an FLT3 Mutation. Tzogani, K., Røshol, H., Olsen, HH., et al.[2021]

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 (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]

References

1. Japan pubmed.ncbi.nlm.nih.gov

[Pharmacological and clinical profile of gilteritinib (Xospata® tablets 40 mg), a therapeutic agent for relapsed or refractory FLT3-mutated acute myeloid leukemia]. [2021]

2. 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]

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

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

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

Reformulating acute myeloid leukemia: liposomal cytarabine and daunorubicin (CPX-351) as an emerging therapy for secondary AML. [2020]

5. Switzerland pubmed.ncbi.nlm.nih.gov

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

6. France pubmed.ncbi.nlm.nih.gov

Gilteritinib: A Review in Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukaemia. [2021]

7. England 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. [2022]

8. England pubmed.ncbi.nlm.nih.gov

The European Medicines Agency Review of Gilteritinib (Xospata) for the Treatment of Adult Patients with Relapsed or Refractory Acute Myeloid Leukemia with an FLT3 Mutation. [2021]

9. United States 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. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

CPX-351 (vyxeos) in AML. [2021]