Chemotherapy Combination for Leukemia

Overseen By Gautam Borthakur

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Pregnancy, Lactation

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: 11

270 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining chemotherapy drugs with a targeted therapy for treating newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). The treatment includes chemotherapy drugs such as Cytarabine and Fludarabine Phosphate, which kill cancer cells, and a targeted therapy, Gemtuzumab Ozogamicin, which specifically attacks cancer cells with certain markers. The study aims to assess the efficacy of these treatments together and identify any side effects. Individuals who have not yet received treatment for AML or high-risk MDS, particularly those with specific genetic markers, may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

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

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

Research has shown that each drug in this chemotherapy combination for leukemia has specific safety outcomes from previous studies.

Studies indicate that filgrastim-sndz is generally safe and helps reduce infection risk during chemotherapy by increasing white blood cells. The most common side effect is bone pain.

Fludarabine phosphate has been used in over 3,000 cancer patients and has a known safety record, though some serious side effects, such as complications after chemotherapy, have been reported.

Cytarabine-based treatments are well-established for leukemia. Studies have shown they can safely lead to remission (when cancer disappears) in many patients. They are often well-tolerated but can cause side effects like nausea.

Gemtuzumab ozogamicin is a targeted therapy for leukemia. Research has shown it is generally safe, with some risks. It can cause liver issues, similar to other treatments.

Overall, these treatments have known safety records, but they can cause side effects, some of which can be serious. Potential trial participants should discuss these risks with their doctors. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this chemotherapy combination for leukemia because it integrates multiple powerful agents, including Gemtuzumab Ozogamicin, which uniquely targets CD33, a protein often found on leukemia cells. This targeting mechanism allows it to deliver chemotherapy directly to cancer cells, potentially reducing damage to healthy cells compared to traditional treatments like anthracyclines or standalone chemotherapy. Additionally, the combination of Cytarabine and Fludarabine Phosphate enhances the overall effectiveness by attacking cancer cells at different stages of their life cycle. This multi-pronged approach could offer a more effective and possibly less toxic alternative to the current standard of care.

What evidence suggests that this trial's chemotherapy combination could be effective for acute myeloid leukemia or high-risk myelodysplastic syndrome?

Research has shown that a combination of specific drugs yields promising results for treating acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome. In this trial, participants will receive fludarabine phosphate, cytarabine, filgrastim-sndz, gemtuzumab ozogamicin, and idarubicin hydrochloride. Studies have found a high remission rate of 95% in patients using similar treatments, indicating that most patients experienced a significant reduction in their cancer. This combination, known as FLAG-GO, has helped many patients live without their cancer returning. Gemtuzumab ozogamicin is particularly noteworthy because it targets specific receptors on cancer cells, delivering a powerful drug directly to kill them. These findings suggest this treatment could be a strong option for fighting these aggressive blood cancers. ^{6 7 8 9 10}

Who Is on the Research Team?

Gautam Borthakur, M.D.

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. It's open to those with certain organ dysfunctions, who may receive adjusted doses. Participants must be able to consent and use effective contraception. Those with up to one prior treatment cycle are included if initial good-risk cytogenetics were missed.

Inclusion Criteria

Patients must provide written consent

I have had only one round of initial cancer treatment.

Patients of childbearing potential should practice effective methods of contraception

Exclusion Criteria

Pregnant and lactating females

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Remission Induction

Patients receive filgrastim-sndz, fludarabine phosphate, cytarabine, and gemtuzumab ozogamicin. Patients not in remission may repeat induction therapy.

5 days

Daily visits for 5 days

Post-Remission Therapy

Patients receive a combination of filgrastim-sndz, fludarabine phosphate, cytarabine, gemtuzumab ozogamicin, and idarubicin hydrochloride. Treatment repeats every 4-6 weeks for up to 6 courses.

4-6 weeks per course

Further Modification of Post-Remission Therapy

Patients older than 60 or with significant comorbidities may receive decitabine. Treatment repeats every 4-6 weeks for up to 12 courses.

4-6 weeks per course

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

2 years

Every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Cytarabine
• Decitabine
• Filgrastim-sndz
• Fludarabine Phosphate
• Gemtuzumab Ozogamicin

Trial Overview The study tests a combination of chemotherapy drugs (fludarabine phosphate, cytarabine, idarubicin hydrochloride) and a targeted therapy (gemtuzumab ozogamicin), plus filgrastim-sndz to boost the immune system after chemo. The goal is to see how well these treatments work together in killing cancer cells or stopping their growth.

How Is the Trial Designed?

Group I: Treatment (filgrastim, fludara, cytara, gemtuzu, idarubicin) Experimental Treatment 7 Interventions

See Detailed Description

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

Approved in United States as Cytosar-U for:

• Acute myeloid leukemia
• Acute lymphocytic leukemia
• Chronic myeloid leukemia
• Meningeal leukemia

Approved in European Union as Depocyt for:

• Lymphomatous meningitis

Approved in Canada as Cytosar-U for:

• Acute myeloid leukemia
• Acute lymphocytic leukemia
• Chronic myeloid leukemia

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 study involving 53 elderly patients with poor-prognosis acute myeloid leukemia (AML), the combination therapy of gemtuzumab ozogamicin, cytarabine, and growth factors (G-AraMy) achieved an overall response rate of 57%, indicating its efficacy in this challenging population.

The treatment was associated with manageable side effects, primarily myelosuppression, and resulted in a median overall survival of 9 months, suggesting that G-AraMy is a viable option for elderly patients with untreated or refractory AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemtuzumab ozogamicin, cytosine arabinoside, G-CSF combination (G-AraMy) in the treatment of elderly patients with poor-prognosis acute myeloid leukemia. Fianchi, L., Pagano, L., Leoni, F., 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]

In a study of 188 patients with acute myeloid leukemia (AML) in first relapse, gemtuzumab ozogamicin led to a remission rate of 30%, indicating its efficacy as a targeted therapy for leukemia cells expressing CD33.

The treatment was generally safe, with manageable side effects; however, it did result in high rates of neutropenia (98%) and thrombocytopenia (99%), while serious complications like veno-occlusive disease occurred in only 2% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute and long-term toxicities associated with gemtuzumab ozogamicin (Mylotarg) therapy of acute myeloid leukemia. Leopold, LH., Berger, MS., Feingold, J.[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]

In a phase II pilot study involving 30 patients under 65 years old with acute myeloid leukemia (AML), the combination of gemtuzumab-ozogamicin (GO) with fludarabine, intermediate dose cytarabine, and idarubicin (FLAI-GO) achieved a high complete response rate of 90%.

The treatment was well tolerated, with only transient infusion-related side effects reported, and after a median follow-up of 16 months, 80% of patients remained alive, indicating promising efficacy and safety for this regimen in CD33 positive AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemtuzumab-ozogamicin in combination with fludarabine, cytarabine, idarubicin (FLAI-GO) as induction therapy in CD33-positive AML patients younger than 65 years. Candoni, A., Martinelli, G., Toffoletti, E., et al.[2019]

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]

Mylotarg (gemtuzumab ozogamicin) is an FDA-approved treatment for older patients (60+) with CD33-positive acute myeloid leukemia who cannot undergo standard chemotherapy, showing a 30% overall response rate in a study of 142 patients.

While Mylotarg can cause some side effects like myelosuppression and elevated liver enzymes, it has a lower incidence of severe mucositis and infections compared to traditional chemotherapy, indicating a potentially safer profile for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mylotarg: antibody-targeted chemotherapy comes of age. Sievers, EL., Linenberger, M.[2019]

In a compassionate-use study of six pediatric patients with refractory/relapsed CD33+ acute myeloid leukemia (AML) treated with gemtuzumab ozogamicin (GO), one patient achieved remission and another is alive after hematopoietic stem cell transplantation, indicating some potential efficacy in this population.

However, the treatment was associated with significant side effects, including a high incidence of veno-occlusive disease (VOD) in three patients, suggesting that GO should be used with caution in pediatric patients due to these serious complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of gemtuzumab ozogamicin in the treatment of pediatric relapsed/ refractory Acute Myeloid Leukemia. Ünal, E., Sahdev, I.[2016]

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 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]

Citations

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Gemtuzumab ozogamicin with fludarabine, cytarabine, and ... Forty-five patients were enrolled (median age 48 years). Remission rate was 95% with 5% induction deaths. The overall survival (OS) and relapse free survival ( ...

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Effect of fludarabine, cytarabine, filgrastim, and ... FLAG-GO is a highly effective regimen and has resulted in high rate of relapse-free survival in pts with newly diagnosed CBF AML.

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Clinical Trial: NCT00801489 Giving fludarabine phosphate, cytarabine, filgrastim-sndz, gemtuzumab ozogamicin, and idarubicin hydrochloride may kill more cancer cells.

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Gemtuzumab Ozogamicin for Relapsed/Refractory AML Here we take a look at the drug, gemtuzumab ozogamicin, and its efficacy on relapsed or refractory AML.

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The Clinical Safety and Efficacy of Cytarabine ... Results: CPX-351 exhibited an adverse event profile that was comparable to that of conventional chemotherapy. It resulted in complete remission rates of 18%-41% ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2017.77.6112

CPX-351 (cytarabine and daunorubicin) Liposome for ... CPX-351 treatment is associated with significantly longer survival compared with conventional 7+3 in older adults with newly diagnosed sAML.

8. ashpublications.org ashpublications.org/ashclinicalnews/news/8741/Intermediate-Dose-of-Cytarabine-as-Effective-as

Intermediate Dose of Cytarabine as Effective as Higher Dose ... Cytarabine-based induction therapy of AML results in remission rates of 60% to 80%; however, the remissions are short-lived. Intensification ...

9. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.70024

Outpatient cytarabine consolidation in acute myeloid leukemia ... Outpatient cytarabine consolidation for select patients is safe and cost-effective without an increased risk of major treatment ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12063066/

The Clinical Safety and Efficacy of Cytarabine ... For newly diagnosed individuals, CPX‐351 led to complete remission rates of 41%–58%, surpassing the 14%–40% associated with standard ...