Flotetuzumab for Acute Myeloid Leukemia

Not currently recruiting at 21 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Children's Oncology Group

Must not be taking: Investigational drugs, Anti-cancer agents, GVHD agents

Disqualifiers: Pregnancy, FAB M3 leukemia, Uncontrolled infection, others

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

Compensation: Varies

Number of Visits: 3

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates the safety and effectiveness of flotetuzumab, a new immunotherapy for treating acute myeloid leukemia (AML) that has returned or resisted other treatments. The study aims to determine the best dose and understand how the treatment interacts with the immune system. It is open to patients with AML whose disease has returned more than once or has not responded to at least two rounds of chemotherapy. Participants will receive a combination of flotetuzumab and another drug, cytarabine, to assess if it can better manage their condition. As a Phase 1 trial, this research focuses on understanding how flotetuzumab works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that flotetuzumab is likely to be safe for humans?

Research has shown that flotetuzumab has been tested in patients with acute myeloid leukemia (AML) who did not respond to treatment or whose cancer returned after treatment. One study found that flotetuzumab was promising and generally well-tolerated. Some patients experienced mild cytokine release syndrome (CRS), a common immune response that can cause fever and tiredness. Another study reported that the side effects were manageable, meaning they were not too severe for most patients. Overall, flotetuzumab has been shown to be safe at certain doses, with some mild side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Flotetuzumab is unique because it targets leukemia cells differently than current treatments. While most therapies for acute myeloid leukemia (AML) focus on killing cells directly, flotetuzumab is a bispecific antibody that engages the body's immune system, specifically recruiting T-cells to attack the cancer. This innovative approach could potentially enhance the body's natural defenses against leukemia, offering a novel way to combat the disease. Researchers are particularly excited about its potential to provide benefits for patients who may not respond to existing chemotherapy options.

What evidence suggests that flotetuzumab might be an effective treatment for acute myeloid leukemia?

Research has shown that flotetuzumab may benefit patients with difficult-to-treat acute myeloid leukemia (AML). One study found that patients with this type of AML who achieved complete remission lived for a median of 10.2 months, meaning half lived longer than 10.2 months after treatment. Another study reported a 16.7% complete remission rate with flotetuzumab. In this trial, participants will receive a combination of flotetuzumab and cytarabine. Flotetuzumab targets specific markers on cancer cells, aiding the immune system in attacking them. These findings suggest that flotetuzumab could be a promising treatment for those with limited options. ^{2 3 5 6 7}

Who Is on the Research Team?

Adam J Lamble

Principal Investigator

Pediatric Early Phase Clinical Trial Network

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7885824/

Flotetuzumab as salvage immunotherapy for refractory ... In PIF/ER AML patients who achieved CR or CRh, the median OS was 10.2 months, with 6- and 12-month survival rates of 75% and 50%, respectively. The observation ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04582864

Flotetuzumab for Relapsed Acute Myeloid Leukemia (AML) ... The investigators hypothesize that flotetuzumab for relapsed AML following allo-HCT will be safe, tolerable and may facilitate preferential immune effector ...

3. ashpublications.org ashpublications.org/ashclinicalnews/news/3678/Preliminary-Results-Show-Flotetuzumab-Well

Preliminary Results Show Flotetuzumab Well-Tolerated and ... Flotetuzumab is a bispecific antibody that targets both CD3 and CD123, which has been shown to be highly expressed on AML leukemic blasts and ...

4. ir.macrogenics.com ir.macrogenics.com/news-releases/news-release-details/macrogenics-announces-publication-flotetuzumab-interim-phase-12

Press Release This PIF/ER AML subset of patients showed a 16.7% (5/30) complete remission (CR) rate and a combined CR and complete remission with partial hematological ...

5. aml-hub.com aml-hub.com/medical-information/safety-and-efficacy-of-flotetuzumab-in-patients-with-rr-aml

Safety and efficacy of flotetuzumab in patients with R/R AML Flotetuzumab is a promising treatment option for patients with PIF/ER AML who have poor prognosis and limited treatment options.

6. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/6209/487206/Safety-and-Activity-of-Flotetuzumab-in-Pediatric

Safety and Activity of Flotetuzumab in Pediatric and Young ... Despite the frequent occurrence of mild CRS and CLS, flotetuzumab was determined to be safe and tolerable at the RP2D of 500 ng/kg/day (DL1) ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0006497119811539

Preliminary Results of a Phase 1 Study of Flotetuzumab ... Flotetuzumab in R/R AML and MDS demonstrated evidence of anti-leukemic activity (ORR 43%) with a manageable safety profile. This program advances an immune- ...