Flotetuzumab for Acute Myeloid Leukemia

Recruiting at 19 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Children's Oncology Group

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 6 months

16 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial studies the side effects, best dose of flotetuzumab and how well it works in treating patients with acute myeloid leukemia (AML) that has come back (recurrent) or has not responded to treatment (refractory). This study also determines the safest dose of flotetuzumab to use in children with AML. As an immunotherapy, flotetuzumab may also cause changes in the body's normal immune system, which are also under study in this trial.

Will I have to stop taking my current medications?

The trial requires that you stop taking other anti-cancer agents and certain medications like cyclosporine or tacrolimus before starting the study, except for hydroxyurea, which can be continued until 24 hours before the trial begins. If you're on steroids, you need to stop them at least 7 days before enrolling, unless they're for hormone replacement.

How is the drug Flotetuzumab unique for treating acute myeloid leukemia?

Flotetuzumab is unique because it is a type of immunotherapy that uses a bispecific antibody to engage the immune system to target and destroy leukemia cells, which is different from traditional chemotherapy that directly kills cancer cells. ^{1 2 3 4 5}

Research Team

Adam J Lamble

Principal Investigator

Pediatric Early Phase Clinical Trial Network

Eligibility Criteria

This trial is for children with acute myeloid leukemia (AML) that has returned or hasn't responded to treatment. They must weigh at least 17 kg, have recovered from previous treatments' side effects, and not been treated with flotetuzumab before. Patients should have a certain level of organ function and blood counts, no history of certain genetic syndromes (except Down syndrome), and not be on specific medications that could interfere with the study.

Inclusion Criteria

My condition did not improve after 2 or more chemotherapy cycles.

I weigh at least 17 kilograms.

Shortening fraction of >/= 27% by echocardiogram, or ejection fraction of >/= 50% by gated radionuclide study

Exclusion Criteria

I am not on any cancer treatments, except possibly hydroxyurea.

I do not have any infections that are currently uncontrolled.

Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Pre-Treatment

Patients receive cytarabine intrathecally on days -6 to 0 prior to cycle 1

1 week

1 visit (in-person)

Treatment

Patients receive flotetuzumab IV continuously for 28 days. Treatment repeats every 29 days for up to 6 cycles

6 months

Continuous monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

1 visit (in-person)

Treatment Details

Interventions

• Flotetuzumab

Trial Overview The trial is testing the safety and optimal dose of flotetuzumab in pediatric patients. Flotetuzumab is an immunotherapy drug designed to target AML cells. The study will also observe how well it works against recurrent or refractory AML in children, as well as its impact on the immune system.

Participant Groups

Group I: Treatment (cytarabine, flotetuzumab) Experimental Treatment 2 Interventions

Patients receive cytarabine IT on days -6 to 0 prior to cycle 1. Patients may receive additional doses of cytarabine on day 1 of subsequent cycles per physician discretion. Patients also receive flotetuzumab IV continuously for 28 days. Treatment repeats every 29 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Acute myeloid leukemia (AML) has the lowest survival rate among leukemias, particularly affecting elderly patients, highlighting the urgent need for new treatment strategies.

Emerging therapies such as Gemtuzumab ozogamicin for CD33-positive AML and selective FLT3 inhibitors show promise in improving survival rates, indicating potential advancements in the management of this challenging disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidemiology and clinical burden of acute myeloid leukemia. Redaelli, A., Lee, JM., Stephens, JM., et al.[2007]

Midostaurin, when combined with standard chemotherapy (cytarabine and daunorubicin), significantly improves event-free survival, disease-free survival, and overall survival in patients with newly diagnosed FLT3-mutated acute myeloid leukemia (AML), based on a phase III trial.

The treatment with midostaurin is considered safe, showing no significant difference in overall toxicity compared to placebo, although it was associated with a higher incidence of grade 3 to 5 anemia and rash.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Midostaurin in Combination With Standard Chemotherapy for Treatment of Newly Diagnosed FMS-Like Tyrosine Kinase 3 (FLT3) Mutation-Positive Acute Myeloid Leukemia. Kim, M., Williams, S.[2019]

The combination of ficlatuzumab, an anti-HGF antibody, with cytarabine showed a favorable safety profile in a phase Ib trial with 17 patients, establishing 20 mg/kg as the recommended dose and achieving a 53% overall response rate with all complete remissions.

The treatment effectively suppressed the p-MET pathway, and high-dimensional analyses revealed that interferon response genes could predict adverse outcomes, highlighting the potential for personalized treatment strategies in acute myeloid leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of MET Signaling with Ficlatuzumab in Combination with Chemotherapy in Refractory AML: Clinical Outcomes and High-Dimensional Analysis. Wang, VE., Blaser, BW., Patel, RK., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Epidemiology and clinical burden of acute myeloid leukemia. [2007]

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

Randomized phase IIb study of low-dose cytarabine and lintuzumab versus low-dose cytarabine and placebo in older adults with untreated acute myeloid leukemia. [2022]

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

Integration of monoclonal antibodies and immunoconjugates into the treatment of acute myeloid leukemia. [2008]

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

Midostaurin in Combination With Standard Chemotherapy for Treatment of Newly Diagnosed FMS-Like Tyrosine Kinase 3 (FLT3) Mutation-Positive Acute Myeloid Leukemia. [2019]

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

Inhibition of MET Signaling with Ficlatuzumab in Combination with Chemotherapy in Refractory AML: Clinical Outcomes and High-Dimensional Analysis. [2022]