Niclosamide for Pediatric Acute Myeloid Leukemia

Recruiting at 1 trial location

Overseen By Nancy Sweeters

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Stanford University

Must not be taking: Investigational agents

Disqualifiers: Acute promyelocytic leukemia, CNS leukemia, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 30 days

16 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for children and young adults with acute myeloid leukemia (AML) who have not responded to other therapies. Researchers are testing niclosamide, a medication traditionally used for infections, alongside a standard drug called cytarabine. The goal is to determine the right dose of niclosamide to help fight AML. Children and young adults with AML that has returned or not improved after at least two rounds of treatment might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment approach.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot have received anticancer therapy within 2 weeks before starting the study treatment. Hydroxyurea is allowed to control high white blood cell counts.

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

Research has shown that niclosamide has been tested on cancer cells from children with acute myeloid leukemia (AML) and proved effective against these cells. In earlier studies with mice, niclosamide significantly slowed the disease and even extended the mice's lifespan, suggesting potential effectiveness in humans.

This trial tests niclosamide with another drug, cytarabine. The FDA has already approved niclosamide for treating tapeworm infections, indicating its prior safe use in humans. However, this trial is in an early stage, focusing on determining the right dose and monitoring for side effects. Researchers are still collecting safety information. Participants will be closely monitored to ensure they tolerate the treatment well. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about niclosamide for pediatric acute myeloid leukemia (AML) because it offers a fresh approach compared to traditional chemotherapy. Most treatments for AML work by killing rapidly dividing cells indiscriminately, but niclosamide targets a specific pathway called the Wnt/β-catenin signaling pathway, which is crucial for cancer cell survival. This unique mechanism could mean fewer side effects and more precise targeting of cancer cells. Additionally, niclosamide is an oral medication, potentially making treatment easier and more comfortable for young patients.

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

Research has shown that niclosamide may help treat acute myeloid leukemia (AML). In studies with mice that had human AML, niclosamide slowed the disease and extended the mice's lifespan. This treatment appears to work by inducing natural cell death in cancer cells and enhancing the effects of chemotherapy. Early results also suggest that niclosamide makes AML cells in children more responsive to treatment. These findings offer hope that niclosamide could be a viable option for treating AML in children. Participants in this trial will receive different dosages of niclosamide to evaluate its effectiveness and safety. ^{1 3 4 5 6}

Who Is on the Research Team?

Kathleen Sakamoto, M.D., Ph.D

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for pediatric patients aged 2-25 with relapsed/refractory acute myeloid leukemia (AML) who have failed previous therapies. Participants must have adequate liver and kidney function, a minimum expected lifespan of 4 weeks, and be able to take oral or nasogastric medications. They should not be pregnant or breastfeeding and must agree to use contraception.

Inclusion Criteria

Life expectancy of greater than 4 weeks

My kidney function is within the required range for the study.

I am between 2 and 25 years old.

Exclusion Criteria

I have side effects from cancer treatment that haven't fully gone away, except for hair loss.

My leukemia has spread to my brain but may be treatable with specific chemotherapy.

I have an ongoing, untreated infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive niclosamide in combination with cytarabine with dose escalation to determine dose-limiting toxicity

30 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Niclosamide

Trial Overview The study tests the effects of increasing doses of Niclosamide combined with cytarabine in young patients with AML that has returned after treatment or hasn't responded to at least two chemotherapy cycles. The goal is to find an effective dose for this specific condition.

How Is the Trial Designed?

Group I: Niclosamide 800 mg/m2 /day divided BID Experimental Treatment 1 Intervention

Group II: Niclosamide 500 mg/m2 /day divided BID Experimental Treatment 1 Intervention

Group III: Niclosamide 250 mg/m2 /day divided BID Experimental Treatment 1 Intervention

Group IV: Niclosamide 1200 mg/m2 /day divided BID Experimental Treatment 1 Intervention

Niclosamide is already approved in European Union for the following indications:

Approved in European Union as Niclosamide for:

• Tapeworm infections

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

The Leukemia and Lymphoma Society

Collaborator

Trials

87

Recruited

26,200+

Pediatric Cancer Research Foundation (PCRF)

Collaborator

CURE Childhood Cancer, Inc.

Collaborator

Trials

5

Recruited

230+

Published Research Related to This Trial

In a study involving 36 children undergoing chemotherapy, dexamethasone was found to be the most effective antiemetic, preventing vomiting in 54% of chemotherapy cycles and reducing its intensity in others.

Other antiemetic drugs like Fenactil, Torecan, Aviomarin, and Primperan showed similar efficacy to placebo, indicating they may not be effective in preventing chemotherapy-induced vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Assessment of the efficacy of drugs used in prevention of vomiting during anticancer therapy in children]. Gadomski, A., Zmudzka, I., Wójtowicz, H.[2008]

Venetoclax, an oral BCL-2 inhibitor, has shown promising efficacy in treating acute myeloid leukemia (AML) in elderly patients who cannot undergo intensive chemotherapy, with complete remission rates of 66.4% and 48% in phase III trials.

The introduction of venetoclax-based therapies has significantly improved treatment options for these patients, but further studies are needed to evaluate the long-term durability of responses and to explore its effectiveness compared to traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax for the treatment of elderly or chemotherapy-ineligible patients with acute myeloid leukemia: a step in the right direction or a game changer? Agarwal, S., Kowalski, A., Schiffer, M., et al.[2022]

In a study involving 9 patients with acute leukemia undergoing induction chemotherapy, the combination of amikacin (AMK) and cephapirin (CEPR) showed varying levels of effectiveness, with 1 case being markedly effective and 2 cases effective.

No adverse effects were observed from the treatment, suggesting that AMK and CEPR can be safely used as a first-line option for managing infections during chemotherapy in acute leukemia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Experience in combination therapy with amikacin and cephapirin for infections complicated with acute leukemia during induction chemotherapy]. Hasegawa, S., Nakao, I.[2016]

Lenvatinib demonstrated a dose-dependent inhibition of acute myeloid leukemia (AML) cell growth in vitro, suggesting its potential as an effective treatment option.

In vivo studies showed that lenvatinib significantly restricted the growth of AML tumors in mice, indicating its efficacy in a living organism model.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The multiple-kinase inhibitor lenvatinib inhibits the proliferation of acute myeloid leukemia cells. Feng, F., Li, X., Li, R., et al.[2023]

Acute myeloid leukemia (AML) remains challenging to treat due to high rates of drug resistance, with about 60% of patients initially responding to standard chemotherapy but most eventually relapsing or developing resistance.

New strategies to combat chemoresistance to the standard drug cytarabine (Ara-C) include using synergistic agents like MNKI-8e and metformin, as well as treatments that minimize damage to healthy cells, which could improve outcomes for AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibitors of Chemoresistance Pathways in Combination with Ara-C to Overcome Multidrug Resistance in AML. A Mini Review. Fajardo-Orduña, GR., Ledesma-Martínez, E., Aguiñiga-Sánchez, I., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5796975/

Niclosamide suppresses acute myeloid leukemia cell ... Niclosamide significantly inhibited the progression of disease in AML patient-derived xenograft (PDX) mice, and prolonged survival of PDX mice. Niclosamide also ...

2. bloodcancerunited.org bloodcancerunited.org/research/award/niclosamide-treatment-relapsedrefractory-pediatric-acute-myeloid-leukemia

Niclosamide for the Treatment of Relapsed/Refractory ... Our preliminary data demonstrated that AML cells from children are sensitive to niclosamide alone and enhances the effects of chemotherapy. Our ...

3. intechopen.com intechopen.com/chapters/1198561

Repurposing Niclosamide for Treatment of Acute Myeloid ... In acute myelogenous leukemia (AML), NIC has been shown to induce caspase-dependent apoptosis by inhibiting the NF-kβ and increasing ROS levels [34]. In ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10119960/

Emerging drugs targeting cellular redox homeostasis to ... The aim of this review is to discuss some drugs that induce oxidative stress to direct new goals for future research focusing on redox imbalance as an ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1471489225000426

Precision medicine and immunotherapeutic approaches for ... Event-free survival (EFS) and overall survival (OS) of paediatric patients with acute myeloid leukaemia (AML) has increased due to chemotherapy intensification, ...

6. trialx.com trialx.com/clinical-trials/listings/258067/niclosamide-in-pediatric-patients-with-relapsed-and-refractory-aml/?&geo_lat=37.36883&geo_lng=-122.0363496&radius=10&place=Sunnyvale&user_country=United%20States

Niclosamide in Pediatric Patients With Relapsed and ... Clinical trial for Acute Myeloid Leukemia (AML) , Niclosamide in Pediatric Patients With Relapsed and Refractory AML.