Gemtuzumab Ozogamicin for Acute Myeloid Leukemia

Recruiting at 1 trial location

Overseen By Mary-Elizabeth Percival

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Washington

Must not be taking: Investigational agents

Disqualifiers: Chemotherapy, Radiation, Uncontrolled illness, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 5 weeks

36 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies the how well fractionated gemtuzumab ozogamicin works in treating measurable residual disease in patients with acute myeloid leukemia. Gemtuzumab ozogamicin is a monoclonal antibody, called gemtuzumab, linked to a chemotherapy drug, called ozogamicin. Gemtuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD33 receptors, and delivers a chemotherapy known as calicheamicin to kill them.

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, you cannot have had chemotherapy or radiation therapy within 14 days before starting the study, and you cannot be on other investigational drugs.

What data supports the effectiveness of the drug Gemtuzumab Ozogamicin (Mylotarg) for treating acute myeloid leukemia?

Research shows that Gemtuzumab Ozogamicin can lead to complete remission (when cancer symptoms disappear) or partial remission in about 25% of adults with a specific type of leukemia (CD33-positive AML) who have relapsed. It is especially useful for patients over 60 who cannot undergo other chemotherapy treatments. ^{1 2 3 4 5}

Is Gemtuzumab Ozogamicin safe for humans?

Gemtuzumab Ozogamicin, also known as Mylotarg, has been associated with some serious side effects, including liver problems and a condition called veno-occlusive disease (a liver condition that can block blood flow). However, it is generally well tolerated by most patients, and its safety has been supported by various studies, leading to its approval for certain types of leukemia. ^{1 3 5 6 7}

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

Gemtuzumab Ozogamicin is unique because it combines a monoclonal antibody with a powerful cancer-killing agent, specifically targeting the CD33 protein found on leukemia cells. This targeted approach allows it to be used in patients who are not eligible for other chemotherapy options, especially those over 60 years old with relapsed acute myeloid leukemia. ^{1 3 4 8 9}

Research Team

Mary-Elizabeth Percival

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

This trial is for people aged 2 and older with Acute Myeloid Leukemia (AML) who have already had at least one round of standard chemo. They must show minimal remaining disease, be in good enough health to perform daily activities, and not have certain types of AML like APL. Pregnant women can't join, and those able to conceive must test negative for pregnancy.

Inclusion Criteria

My bilirubin levels are within twice the normal range, or I have Gilbert's disease.

My child's bilirubin levels are within the normal range for their age, or they have Gilbert's disease.

My kidney function is good, with a creatinine level of 2.0 mg/dL or less.

Exclusion Criteria

I have not had chemotherapy or radiation in the last 14 days.

Subjects may not be receiving other investigational agents.

I do not have any severe illnesses that would stop me from following the study's requirements.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive gemtuzumab ozogamicin intravenously on days 1, 4, 7. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.

5 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Gemtuzumab Ozogamicin

Trial Overview The trial tests fractionated Gemtuzumab Ozogamicin (GO), a targeted antibody-chemo combo that seeks out cancer cells by attaching to CD33 receptors on their surface. It's given to patients whose AML isn't fully gone after treatment but is low ('measurable residual disease').

Participant Groups

Group I: Treatment (gemtuzumab ozogamicin) Experimental Treatment 2 Interventions

Patients receive gemtuzumab ozogamicin IV on days 1, 4, 7. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity. Responders and non-responders, without significant adverse events during the first course, may receive a second course of gemtuzumab ozogamicin within 60 days after course 1.

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?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

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

Findings from Research

In a study of 142 patients with CD33-positive acute myeloid leukemia (AML) in first relapse, 30% achieved remission after treatment with Mylotarg (gemtuzumab ozogamicin), indicating its efficacy as a targeted chemotherapy agent.

While Mylotarg was associated with some adverse effects, such as myelosuppression and elevated liver enzymes, it had a favorable safety profile overall, with low incidences of severe nausea, vomiting, and no significant cardiotoxicity or hair loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. Sievers, EL., Larson, RA., Stadtmauer, EA., et al.[2022]

Gemtuzumab ozogamicin (GO) was effective in treating CD33-positive acute myeloid leukemia (AML), achieving a 26% remission rate among 277 patients, with a median recurrence-free survival of 6.4 months for those who achieved complete remission.

The safety profile of GO was generally acceptable, with high rates of expected side effects like neutropenia (98%) and thrombocytopenia (99%), but relatively low incidences of severe infections such as sepsis (17%) and pneumonia (8%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence. Larson, RA., Sievers, EL., Stadtmauer, EA., et al.[2022]

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]

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

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

Spotlight on gemtuzumab ozogamicin in acute myeloid leukaemia. Fenton, C., Perry, CM.[2018]

Gemtuzumab ozogamicin, the first antibody-drug conjugate approved for CD33-positive acute myeloid leukemia (AML), was initially withdrawn from the market due to lack of clinical benefit, but later studies with new dosing regimens demonstrated its efficacy.

Pharmacokinetic modeling revealed significant relationships between drug exposure and clinical outcomes, leading to its full FDA approval in 2017 for both newly diagnosed and relapsed AML in adults and children aged 2-17 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic/Pharmacodynamic Modeling to Support the Re-approval of Gemtuzumab Ozogamicin. Fostvedt, LK., Hibma, JE., Masters, JC., et al.[2020]

Gemtuzumab ozogamicin (Mylotarg) is an effective treatment for relapsed acute myeloid leukemia (AML), targeting CD33 on leukemic cells and using a potent cytotoxic agent to induce cell death, with promising results from early phase I/II studies.

While it shows significant efficacy, there are concerns about potential adverse effects, including veno-occlusive disease and increased liver toxicity, which are important considerations as it is being tested in new patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early phase I/II trials with gemtuzumab ozogamicin (Mylotarg) in acute myeloid leukemia. Nabhan, C., Tallman, MS.[2019]

Gemtuzumab ozogamicin is a targeted chemotherapy agent that effectively treats relapsed acute myeloid leukemia (AML) by specifically targeting the CD33 antigen on leukemic cells, which helps reduce overall toxicity compared to conventional chemotherapy.

This treatment has shown particular efficacy and tolerability in older patients (60 years and above) with relapsed AML, providing a crucial option for those who often have limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nursing implications of mylotarg: a novel antibody-targeted chemotherapy for CD33+ acute myeloid leukemia in first relapse. Shannon-Dorcy, K.[2012]

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]

Gemtuzumab ozogamicin is an effective treatment option for relapsed acute myeloid leukemia (AML), as demonstrated in Phase II trials, showing promising results in patients with poor prognosis.

While gemtuzumab ozogamicin has an acceptable safety profile as a standalone treatment, there is a significant risk of veno-occlusive disease of the liver when used in combination with chemotherapy or during hematopoietic stem cell transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemtuzumab ozogamicin in the treatment of acute myeloid leukemia. Stadtmauer, EA.[2019]

References

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

Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. [2022]

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

Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence. [2022]

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

Gemtuzumab ozogamicin: a review of its use in acute myeloid leukaemia. [2022]

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

Spotlight on gemtuzumab ozogamicin in acute myeloid leukaemia. [2018]

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

Pharmacokinetic/Pharmacodynamic Modeling to Support the Re-approval of Gemtuzumab Ozogamicin. [2020]

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

Early phase I/II trials with gemtuzumab ozogamicin (Mylotarg) in acute myeloid leukemia. [2019]

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

Nursing implications of mylotarg: a novel antibody-targeted chemotherapy for CD33+ acute myeloid leukemia in first relapse. [2012]

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

Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia. [2022]

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

Gemtuzumab ozogamicin in the treatment of acute myeloid leukemia. [2019]