Niclosamide for Pediatric Acute Myeloid Leukemia

Recruiting at1 trial location

Overseen by Kathleen Sakamoto, M.D., Ph.D

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Stanford University

Must not be taking: Investigational agents

Disqualifiers: Acute promyelocytic leukemia, CNS leukemia, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of two drugs, niclosamide and cytarabine, to treat children with a type of leukemia that has come back or hasn't responded to other treatments. The goal is to see if niclosamide can help cytarabine work better by making cancer cells easier to destroy. Niclosamide is being tested to see if it can help destroy cancer cells more effectively.

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.

How is the drug Niclosamide unique in treating pediatric acute myeloid leukemia?

Niclosamide is unique because it is being explored for its potential to overcome drug resistance in acute myeloid leukemia (AML), which is a major challenge with current treatments. It may work synergistically with existing chemotherapy drugs like cytarabine to enhance their effectiveness. ^{1 2 3 4 5}

Research Team

Kathleen Sakamoto, M.D., Ph.D

Principal Investigator

Stanford University

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Niclosamide (Anti-helminthic)

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.

Participant Groups

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

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Dr. Richard A. Miller

Stanford University

Chief Executive Officer since 2023

Stanford University, MD

Dr. Robert Schott

Stanford University

Chief Medical Officer since 2021

University of Michigan, MD

Findings from Research

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]

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 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]

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]

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]

References

1. Japan pubmed.ncbi.nlm.nih.gov

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

2. England 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? [2022]

3. Poland pubmed.ncbi.nlm.nih.gov

[Assessment of the efficacy of drugs used in prevention of vomiting during anticancer therapy in children]. [2008]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Inhibitors of Chemoresistance Pathways in Combination with Ara-C to Overcome Multidrug Resistance in AML. A Mini Review. [2021]

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

The multiple-kinase inhibitor lenvatinib inhibits the proliferation of acute myeloid leukemia cells. [2023]