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

Trial Summary

What is the purpose of this trial?

This phase II trial studies the side effects and how well fludarabine phosphate, cytarabine, filgrastim-sndz, gemtuzumab ozogamicin, and idarubicin hydrochloride work in treating patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Drugs used in chemotherapy, such as fludarabine phosphate, cytarabine, and idarubicin hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Gemtuzumab ozogamicin is a monoclonal antibody, called gemtuzumab, linked to a antitumor drug, called calicheamicin. 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 calicheamicin to kill them. Colony-stimulating factors, such as filgrastim-sndz, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Giving fludarabine phosphate, cytarabine, filgrastim-sndz, gemtuzumab ozogamicin, and idarubicin hydrochloride may kill more cancer cells.

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.

What data supports the effectiveness of the drug combination including gemtuzumab ozogamicin for leukemia?

Gemtuzumab ozogamicin, when combined with other drugs like daunorubicin and cytarabine, has been shown to improve event-free survival in patients with newly diagnosed acute myeloid leukemia (AML), increasing it from 8.8 months to 13.6 months. This suggests that the drug combination can be more effective than some standard treatments for AML. ^{1 2 3 4 5}

Is gemtuzumab ozogamicin (Mylotarg) generally safe for humans?

Gemtuzumab ozogamicin (Mylotarg) has been studied in patients with acute myeloid leukemia and is generally considered safe, but it can cause side effects like nausea, fever, and low blood cell counts. Some serious side effects include liver problems and veno-occlusive disease (a liver condition), but these are less common. ^{3 4 6 7 8}

What makes the chemotherapy combination of Cytarabine, Fludarabine Phosphate, and Gemtuzumab Ozogamicin unique for treating leukemia?

This treatment is unique because it combines Gemtuzumab Ozogamicin, a targeted therapy that attaches to a specific protein (CD33) on leukemia cells, with other chemotherapy drugs, potentially improving outcomes for patients with CD33-positive acute myeloid leukemia (AML). Gemtuzumab Ozogamicin is an antibody-drug conjugate that delivers a potent toxin directly to cancer cells, which may enhance the effectiveness of the chemotherapy regimen. ^{1 2 9 10 11}

Research Team

Gautam Borthakur, M.D.

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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]

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]

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 (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]

References

1. 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]

2. England 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. [2019]

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

Mylotarg: antibody-targeted chemotherapy comes of age. [2019]

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

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

5. Turkey pubmed.ncbi.nlm.nih.gov

Use of gemtuzumab ozogamicin in the treatment of pediatric relapsed/ refractory Acute Myeloid Leukemia. [2016]

6. 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]

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

Acute and long-term toxicities associated with gemtuzumab ozogamicin (Mylotarg) therapy of acute myeloid leukemia. [2019]

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

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

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

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

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

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

11. England 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. [2020]