MEGO Therapy for Acute Myeloid Leukemia

Overseen By Linda Fukas, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Robert Redner, MD

Must not be taking: Mitoxantrone, Etoposide, GO

Disqualifiers: APL, Relapsed leukemia, 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

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of a combination of three drugs—mitoxantrone, etoposide, and gemtuzumab ozogamicin—for patients with acute myeloid leukemia (AML) who did not improve after their first treatment. Researchers seek to understand both the effectiveness and any side effects of this drug combination. Suitable candidates have AML or a related condition, have not responded to initial treatments, and have a specific type of leukemia cell present in their bone marrow. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Research has shown that a combination of three drugs—mitoxantrone, etoposide, and gemtuzumab ozogamicin—was tested in patients with acute myeloid leukemia who did not respond to initial treatments. Studies have found that most patients tolerated this treatment well. Some experienced side effects, which are common with cancer treatments. These side effects included low blood cell counts and infections, but they were mostly manageable with medical care.

Importantly, other studies have used this combination, indicating it can be safe for many patients. Since this is a phase 2 trial, researchers have some evidence that the treatment is safe enough for further testing. However, everyone reacts differently, so careful monitoring during treatment is essential. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of mitoxantrone, etoposide, and gemtuzumab ozogamicin for treating Acute Myeloid Leukemia (AML) because it brings together a unique blend of mechanisms that aren't typically used together in current standard treatments like cytarabine and daunorubicin. Gemtuzumab ozogamicin, in particular, stands out as it is an antibody-drug conjugate, which specifically targets leukemia cells by honing in on the CD33 antigen present on these cells and delivering a potent toxin directly to them. This targeted approach could potentially increase effectiveness while minimizing damage to healthy cells, offering hope for better outcomes in AML treatment.

What evidence suggests that this combination therapy could be effective for acute myeloid leukemia?

In this trial, participants will receive a combination of mitoxantrone, etoposide, and gemtuzumab ozogamicin to treat acute myeloid leukemia (AML) that hasn't responded to initial treatments. Research has shown that this combination can be effective, particularly against cancer cells with the CD33 protein, which is common in leukemia. Patients who received similar treatments in past studies experienced positive results, such as lower leukemia cell counts. This approach leverages each drug's unique method of attacking cancer cells, potentially leading to better outcomes when used together. Overall, evidence suggests this combination could offer new hope for patients with difficult-to-treat AML. ^{1 2 5 6 7}

Who Is on the Research Team?

Redner Robert, MD

Principal Investigator

UPMC Hillman Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) who didn't respond to initial therapy. They must have certain blood and organ function levels, not be pregnant, agree to use contraception, and can't have other active cancers or severe diseases.

Inclusion Criteria

Alanine aminotransferase (ALT) ≤ 2.5 x upper normal limit

Total bilirubin ≤ 2 x upper normal limit

Aspartate aminotransferase (AST) ≤ 2.5 x upper normal limit

Exclusion Criteria

My acute leukemia has returned after treatment.

My leukemia shows two types of cells.

I have previously been treated with mitoxantrone, etoposide, or GO.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mitoxantrone and etoposide on days 1-5 and gemtuzumab ozogamicin on day 6

1 week

Inpatient treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

Long-term follow-up

Participants are monitored for progression-free survival and overall survival

Up to five years

What Are the Treatments Tested in This Trial?

Interventions

• Etoposide
• Gemtuzumab Ozogamicin
• Mitoxantrone

Trial Overview The study tests a combination of drugs: mitoxantrone, etoposide, and gemtuzumab ozogamicin (MEGO), in patients whose AML/MDS did not improve after first-line treatment. It's an open-label phase II trial focusing on the effectiveness and safety of this regimen.

How Is the Trial Designed?

Group I: mitoxantrone + etoposide + gemtuzumab ozogamicin Experimental Treatment 1 Intervention

10 mg/m2 mitoxantrone days 1-5 + 100mg/m2 etoposide days 1-5 + 3mg/m2 gemtuzumab ozogamicin on day 6

Etoposide is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Etoposide for:

• Testicular cancer
• Small cell lung cancer
• Non-Hodgkin lymphoma
• Acute myeloid leukemia

Approved in European Union as Etoposide for:

• Testicular cancer
• Small cell lung cancer
• Non-Hodgkin lymphoma
• Acute myeloid leukemia

Approved in Canada as Etoposide for:

• Testicular cancer
• Small cell lung cancer
• Non-Hodgkin lymphoma
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

Robert Redner, MD

Lead Sponsor

Trials

2

Recruited

50+

Konstantinos Lontos

Lead Sponsor

Trials

1

Recruited

20+

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

Citations

1. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/6145/489268/Trial-in-Progress-A-Phase-2-Study-of-Mitoxantrone

Trial-in-Progress: A Phase 2 Study of Mitoxantrone, Etoposide ... Pre-clinical data suggest that GO is most effective when it saturates CD33 which happens in low-burden disease (Van der Velden et al Leukemia ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00660036

Phase I/II Study of Mitoxantrone, Etoposide and ... The purpose of this study is to investigate the combination of gemtuzumab ozogamicin, mitoxantrone and etoposide as second line therapy in patients with acute ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03839446

Phase II Study of the Combination of Mitoxantrone, ... Combination of Mitoxantrone, Etoposide and Gemtuzumab Ozogamicin (MEGO) for Patients With Acute Myeloid Leukemia Refractory to Initial Standard Induction ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9221325/

Phase 1/2 Trial of CLAG-M with Dose-Escalated ... These data indicate that CLAG-M/GO3 is safe and leads to superior outcomes than CLAG-M alone in favorable-risk AML/high-grade myeloid neoplasm.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0145212624000341

Efficacy and safety of mitoxantrone, etoposide, and ... Research paper. Efficacy and safety of mitoxantrone, etoposide, and cytarabine for treatment of relapsed or refractory acute myeloid leukemia.

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2019-02782

Mitoxantrone, Etoposide, and Gemtuzumab Ozogamicin in ... This phase II trial studies the side effects of mitoxantrone, etoposide, and gemtuzumab ozogamicin and to see how well they work in treating patients acute ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4558626/

A Report From The Children's Oncology Group - PMC Based on these results, an ongoing phase III trial conducted within the Children's Oncology Group is evaluating the effect of GMTZ when added to standard AML ...