What side effects are associated with this type of intervention?

Common treatments for Acute Myeloid Leukemia (AML) include hypomethylating agents like azacitidine and decitabine, as well as cytarabine. These treatments are associated with side effects such as neutropenia, thrombocytopenia, and anemia, which can lead to increased risk of infections and bleeding. Gastrointestinal symptoms like nausea, vomiting, and diarrhea are also common. Fatigue and injection site reactions may occur. Niclosamide, which targets the Wnt/β-catenin pathway, is being studied for its potential to eradicate leukemia stem cells, but its side effect profile in AML is not yet well-established.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of Acute Myeloid Leukemia (AML). Cytarabine, a cornerstone of AML treatment, inhibits DNA synthesis and has been widely used in various chemotherapy regimens. Other notable FDA-approved drugs include Venetoclax, which targets the BCL-2 protein to induce apoptosis, and Gilteritinib, a FLT3 inhibitor used for specific genetic mutations in AML. Additionally, Azacitidine and Decitabine, both hypomethylating agents, have been approved for AML treatment, particularly in patients who are not candidates for intensive chemotherapy. These drugs, while not directly targeting the Wnt/β-catenin pathway like Niclosamide, represent a broad spectrum of mechanisms aimed at disrupting cancer cell proliferation and survival.

What other types of research exist?

Promising novel alternatives for AML treatment include: <ol> <li>Venetoclax (BCL-2 inhibitor) combined with Azacitidine (HMA) - This combination has shown efficacy in patients with poor-risk cytogenetics.</li> <li></li> </ol> Ivosidenib (IDH1 inhibitor) - Effective when combined with HMAs. 3. Gilteritinib (FLT3 inhibitor) - Shows promise when combined with Azacitidine. 4. Chidamide and Apatinib - Synergistic in reducing cell viability and inducing apoptosis in AML stem and progenitor cells. 5. Pan-PIM kinase inhibitors - Demonstrated antiproliferative activity and synergy with Cytarabine in AML models.

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Anti-helminthic

Niclosamide for Pediatric Acute Myeloid Leukemia

Phase 1

Recruiting

Led By Kathleen M Sakamoto, MD, PhD

Research Sponsored by Stanford University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Serum creatinine ≤ 2.0 mg/dL or estimated creatinine clearance ≥ 30 mL/min (Cockcroft Gault) within 14 days prior to treatment initiation

Has previously failed all available and suitable therapies for AML Disease relapse or the presence of refractory disease after ≥ 2 cycles of chemotherapy must be documented by bone marrow (BM) examination demonstrating > 5% blasts in the BM not attributable to another cause. Administration of hydroxyurea 10 to 20 mg/kg/day PO (maximum 1000 mg PO BID) to control high WBC count is permitted.

Must not have

Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, uncontrolled symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction, at the time of study entry

Known active uncontrolled systemic infection

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 30 days

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While the side effects specific to Niclosamide in this context are not detailed here, potential risks may include typical chemotherapy-related issues such as nausea, fatigue, increased risk of infection due to low blood cell counts, liver toxicity, and allergic reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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My AML has not responded to at least 2 chemotherapy treatments, confirmed by a bone marrow test.

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I am between 2 and 25 years old.

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I have been diagnosed with AML according to WHO standards.

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I can take medications by mouth or through a tube.

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My body surface area is 2.10 m2 or less.

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I am under 16 with a Lansky score over 50, or over 16 with a Karnofsky score over 50%.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have major issues with my digestive system that are uncontrolled.

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I have an ongoing, untreated infection.

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I do not have any uncontrolled illnesses or social situations that would stop me from following the study's requirements.

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I cannot take niclosamide in its current forms.

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I am currently pregnant or breastfeeding.

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I have active hepatitis C.

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I have been diagnosed with a specific type of leukemia (APL).

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I had a bone marrow transplant and am currently experiencing severe GvHD symptoms.

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I have a bleeding disorder like hemophilia.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 30 days

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~30 days

This trial's timeline: 3 weeks for screening, Varies for treatment, and 30 days for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Dose-limiting toxicity

Secondary study objectives

Efficacy of niclosamide treatment clinical response

Side effects data

From 2021 Phase 2 trial • 73 Patients • NCT04399356

21%

Nausea

Skin rash

Vomiting

100%

80%

60%

40%

20%

Study treatment Arm

Control Group

Niclosamide- Experimental Group

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups

Experimental Treatment

Group I: Niclosamide 800 mg/m2 /day divided BIDExperimental Treatment1 Intervention

Group II: Niclosamide 500 mg/m2 /day divided BIDExperimental Treatment1 Intervention

Group III: Niclosamide 250 mg/m2 /day divided BIDExperimental Treatment1 Intervention

Group IV: Niclosamide 1200 mg/m2 /day divided BIDExperimental Treatment1 Intervention

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Niclosamide

2017

Completed Phase 3

~2280

0 / 16Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Acute Myeloid Leukemia (AML) include agents that inhibit key cellular pathways critical for cancer cell survival and proliferation. Niclosamide targets the Wnt/β-catenin signaling pathway, which is often dysregulated in AML, leading to uncontrolled cell growth and survival. By inhibiting this pathway, Niclosamide can reduce tumor cell proliferation and induce apoptosis. Cytarabine, on the other hand, inhibits DNA synthesis by incorporating into DNA during replication, causing chain termination and cell death. This is particularly effective in rapidly dividing cells, such as AML cells. These mechanisms are crucial for AML patients as they directly target the cellular processes that allow leukemia cells to grow and survive, thereby potentially improving treatment outcomes and survival rates.

γ-Catenin Overexpression in AML Patients May Promote Tumor Cell Survival via Activation of the Wnt/β-Catenin Axis.Knockdown of TRIM24 suppresses growth and induces apoptosis in acute myeloid leukemia through downregulation of Wnt/GSK-3β/β-catenin signaling.Molecular targeting in acute myeloid leukemia.