Azacitidine + Gemtuzumab for Acute Myeloid Leukemia

Not currently recruiting at 208 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of combining two drugs, azacitidine (Vidaza) and gemtuzumab ozogamicin (Mylotarg), in treating acute myeloid leukemia (AML) in patients without prior treatments. Azacitidine blocks certain enzymes to stop cancer cell growth, while gemtuzumab ozogamicin targets and kills cancer cells. The trial seeks participants with AML, excluding those with acute promyelocytic leukemia, who have not received significant prior chemotherapy for AML. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that combining azacitidine and gemtuzumab ozogamicin is being studied as a treatment for acute myeloid leukemia (AML) in older adults. Studies suggest that this combination might be safe for patients. One study found that it could serve as a "bridge therapy," helping prepare patients for further treatments like stem cell transplants. This suggests the treatment is manageable enough for key stages of care.

In other research, this combination was tested in patients with AML who had already tried other treatments. The results indicated that the treatment was both safe and possibly effective as a new therapy option. However, side effects can occur because both azacitidine and gemtuzumab are strong cancer-fighting drugs. It is important to discuss potential risks with the trial team to understand what to expect. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Azacitidine combined with Gemtuzumab Ozogamicin for treating Acute Myeloid Leukemia (AML) because it offers a unique approach compared to current standard treatments like chemotherapy and allogeneic stem cell transplantation. Gemtuzumab Ozogamicin is an antibody-drug conjugate that specifically targets CD33, a protein commonly found on leukemia cells, allowing for more precise delivery of the cancer-killing agent directly to the malignant cells. This targeted mechanism potentially reduces damage to healthy cells, which could lead to fewer side effects compared to traditional chemotherapy. Additionally, combining it with Azacitidine, which helps to modify the expression of genes in cancer cells, might enhance its effectiveness and provide a promising new strategy for tackling AML.

What evidence suggests that azacitidine and gemtuzumab ozogamicin might be an effective treatment for acute myeloid leukemia?

Research has shown that using azacitidine with gemtuzumab ozogamicin may help treat acute myeloid leukemia (AML) in older adults. In this trial, participants will receive a combination of azacitidine, which studies have found can stop cancer cells from growing, and gemtuzumab ozogamicin, a special type of medicine that targets and kills cancer cells. Together, these drugs have demonstrated effectiveness in treating difficult cases of AML. Early results suggest this combination might outperform other treatments that have not been successful. ^{1 2 3 6 7}

Who Is on the Research Team?

Sucha Nand

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

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.

My cancer has spread to my brain or spinal cord.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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, 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 (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 (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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3829116/

A phase 2 trial of azacitidine and gemtuzumab ozogamicin ... Data from large studies conducted by SWOG as well as other major oncology groups show very little improvement in the outcomes in elderly patients with AML over ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00766116

Combination 5-azacitidine and Gemtuzumab Ozogamicin ... This study will test an experimental combination of the drugs Mylotarg and 5-azacitidine in the hopes of finding a treatment that may be effective against Acute ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9793740/

Clinical Utility of Azacitidine in the Management of Acute ... The data suggest that oral AZA maintenance is an effective maintenance strategy to prolong survival in high-risk as well as favorable-risk AML ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT00658814

NCT00658814 | Azacitidine and Gemtuzumab Ozogamicin ... 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 ...

5. cttjournal.com cttjournal.com/article/gemtuzumab-ozogamicin-in-combination-with-azacitidine-a-bridge-to-allogeneic-stem-cell

Gemtuzumab ozogamicin in combination with azacitidine ... The combination of gemtuzumab ozogamicin and azacitidine showed therapeutic efficiency in this difficult-to-treat subset of AML patients and can be used as an ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0145212624002042

Combination therapy involving azacitidine for acute ... AZA-Venetoclax Combo Shows 66.4 % Remission in Unfit AML Patients: A significant survival milestone in treating Unfit AML. •. Personalized AML Treatments ...

7. ashpublications.org ashpublications.org/blood/article-abstract/122/20/3432/32112

A phase 2 trial of azacitidine and gemtuzumab ozogamicin ... This trial tested the safety and efficacy of a regimen consisting of hydroxyurea followed by azacitidine, 75 mg/m 2 for 7 days, and gemtuzumab ozogamicin, 3 mg ...