Azacitidine + Gemtuzumab for Acute Myeloid Leukemia

Recruiting at 204 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Azacitidine, Gemtuzumab ozogamicin

Disqualifiers: CNS involvement, Prior malignancy, 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

133 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial is studying the side effects of giving azacitidine together with gemtuzumab ozogamicin to see how well it works in treating older patients with previously untreated acute myeloid leukemia. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Azacitidine may also stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as gemtuzumab ozogamicin, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving azacitidine together with gemtuzumab ozogamicin may kill more cancer cells.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it does mention that prior treatment with certain drugs like azacitidine, decitabine, or gemtuzumab ozogamicin is not allowed, and there should be at least 30 days since prior therapy for myelodysplastic syndrome (MDS) before joining the trial.

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

Research shows that Gemtuzumab Ozogamicin, when combined with other drugs like azacitidine, can be effective in treating certain types of acute myeloid leukemia, especially in older patients or those with specific genetic profiles. In one study, a combination of Gemtuzumab Ozogamicin and azacitidine showed a 41.9% overall response rate in patients with relapsed or difficult-to-treat leukemia. ^{1 2 3 4 5}

What safety information is available for Azacitidine and Gemtuzumab Ozogamicin in treating acute myeloid leukemia?

Gemtuzumab Ozogamicin (Mylotarg) has been associated with serious side effects like veno-occlusive disease (a liver condition) and increased risk of bleeding and low blood cell counts. However, it is generally considered to have an acceptable safety profile when used alone, though caution is advised when combined with other chemotherapy drugs. ^{4 6 7 8 9}

What makes the drug combination of Azacitidine and Gemtuzumab Ozogamicin unique for treating acute myeloid leukemia?

This drug combination is unique because it combines azacitidine, which modifies DNA to stop cancer cell growth, with gemtuzumab ozogamicin, an antibody-drug conjugate that specifically targets and kills CD33-positive leukemia cells. This approach aims to enhance the effectiveness of treatment by using two different mechanisms to attack the cancer. ^{2 3 4 8 10}

Research Team

Sucha Nand

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

This trial is for older patients with untreated acute myeloid leukemia (AML) who haven't had prior AML chemotherapy, except hydroxyurea. They should not be allergic to the study drugs or have a history of certain other cancers within the last 2 years. HIV+ patients can join if they meet specific criteria. Participants must have functioning major organs and no central nervous system involvement by cancer.

Inclusion Criteria

I am not allergic to azacitidine, mannitol, hydroxyurea, or gemtuzumab ozogamicin.

Consent to submit specimens to SWOG repository

Complete remission (CR) or CRi documented within 42 days before registration

Exclusion Criteria

My leukemia is either acute promyelocytic or in a blastic phase of chronic myelogenous.

I've had intense chemotherapy or stem cell support for myelodysplastic syndrome.

I have been treated with azacitidine, decitabine, or gemtuzumab ozogamicin.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Remission Induction Therapy

Patients receive azacitidine IV or SC on days 1-7 and gemtuzumab ozogamicin IV on day 8. A second course may be given if residual leukemia is present.

4 weeks

Consolidation Therapy

Patients receive one course of azacitidine and gemtuzumab ozogamicin as in induction therapy.

4 weeks

Maintenance Therapy

Patients receive azacitidine SC on days 1-7, repeating every 28 days for 4 courses.

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Up to 5 years

Treatment Details

Interventions

• Azacitidine
• Gemtuzumab Ozogamicin

Trial Overview The trial tests azacitidine and gemtuzumab ozogamicin's effectiveness in treating AML when given together. Azacitidine interferes with cell growth enzymes, while gemtuzumab ozogamicin is an antibody that targets and kills cancer cells or delivers toxins to them.

Participant Groups

Group I: Treatment (azacitidine, gemtuzumab) Experimental Treatment 2 Interventions

See Detailed Description

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

Approved in European Union as Vidaza for:

• Acute myeloid leukemia
• Chronic myelomonocytic leukemia
• Myelodysplastic syndromes

Approved in United States as Vidaza for:

• Myelodysplastic syndromes
• Chronic myelomonocytic leukemia

Approved in Canada as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 237 older patients with acute myeloid leukemia, treatment with gemtuzumab ozogamicin (GO) significantly improved overall survival (OS) compared to best supportive care, with a median OS of 4.9 months for GO versus 3.6 months for BSC.

The treatment was well-tolerated, showing similar rates of serious adverse events between the GO and BSC groups, indicating that GO can be a safe and effective first-line therapy for patients unsuitable for intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemtuzumab Ozogamicin Versus Best Supportive Care in Older Patients With Newly Diagnosed Acute Myeloid Leukemia Unsuitable for Intensive Chemotherapy: Results of the Randomized Phase III EORTC-GIMEMA AML-19 Trial. Amadori, S., Suciu, S., Selleslag, D., et al.[2022]

In a phase I/II trial involving 52 adults with acute myeloid leukemia, the combination of vorinostat, azacitidine, and gemtuzumab ozogamicin showed a promising overall response rate of 41.9%, with 10 patients achieving complete remission.

Patients who achieved complete remission had a significantly longer median overall survival of 224.5 days compared to 95 days for those who did not respond to the treatment, highlighting the potential efficacy of this combination therapy in a challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemtuzumab ozogamicin in combination with vorinostat and azacitidine in older patients with relapsed or refractory acute myeloid leukemia: a phase I/II study. Walter, RB., Medeiros, BC., Gardner, KM., et al.[2021]

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, 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 (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 (GO) combined with cytarabine showed promising results in two pediatric patients with relapsed acute myeloid leukemia (AML), significantly reducing minimal residual disease to unprecedented levels.

The treatment had a relatively mild toxicity profile, although it did cause severe but manageable myelosuppression, indicating a need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular response in two children with relapsed acute myeloid leukemia treated with a combination of gemtuzumab ozogamicin and cytarabine. Brethon, B., Auvrignon, A., Cayuela, JM., et al.[2019]

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 (Mylotarg) is an FDA-approved treatment for older patients (60+) with CD33+ acute myeloid leukemia (AML) who cannot undergo chemotherapy, targeting the CD33 antigen found on over 80% of AML cases.

The treatment has shown clinical remissions in patients, although it can cause side effects like fever, chills, and low blood cell counts, indicating the need for careful monitoring during administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mylotarg approved for patients with CD33+ acute myeloid leukemia. Sorokin, P.[2012]

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]

References

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

Gemtuzumab Ozogamicin Versus Best Supportive Care in Older Patients With Newly Diagnosed Acute Myeloid Leukemia Unsuitable for Intensive Chemotherapy: Results of the Randomized Phase III EORTC-GIMEMA AML-19 Trial. [2022]

2. Italy pubmed.ncbi.nlm.nih.gov

Gemtuzumab ozogamicin in combination with vorinostat and azacitidine in older patients with relapsed or refractory acute myeloid leukemia: a phase I/II study. [2021]

3. 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]

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

FDA Approval: Gemtuzumab Ozogamicin for the Treatment of Adults with Newly Diagnosed CD33-Positive Acute Myeloid Leukemia. [2019]

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

Mutational profile and benefit of gemtuzumab ozogamicin in acute myeloid leukemia. [2021]

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

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

7. Italy pubmed.ncbi.nlm.nih.gov

Molecular response in two children with relapsed acute myeloid leukemia treated with a combination of gemtuzumab ozogamicin and cytarabine. [2019]

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

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

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

Mylotarg approved for patients with CD33+ acute myeloid leukemia. [2012]

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

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