Niclosamide in Pediatric Patients With Relapsed and Refractory AML

NCT05188170 | Recruiting Phase 1 FDA Drug

• 5 other identifiers: IRB-61916PEDSHEMAML00076410956587-20NCI-2022-09974
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Protocol is designed to evaluate a niclosamide dose escalation scale in combination with cytarabine as a therapeutic modality for pediatric subjects with relapsed/refractory acute myeloid leukemia.

Conditions

Acute Myeloid Leukemia (AML)

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicity

  Dose-limiting toxicities (DLTs) are defined as any events ≥ Grade 3 that are at least possibly, probably, or definitely related to niclosamide treatment

  30 days

Secondary Outcomes (1)

• Efficacy of niclosamide treatment clinical response

  8 weeks

Study Arms (4)

Niclosamide 250 mg/m2 /day divided BID

EXPERIMENTAL

Drug: Niclosamide

Niclosamide 500 mg/m2 /day divided BID

EXPERIMENTAL

Drug: Niclosamide

Niclosamide 800 mg/m2 /day divided BID

EXPERIMENTAL

Drug: Niclosamide

Niclosamide 1200 mg/m2 /day divided BID

EXPERIMENTAL

Drug: Niclosamide

Interventions

Niclosamide DRUG

Niclosamide will be administered orally for 14 days. Each dose will be followed by backbone chemotherapy

Niclosamide 1200 mg/m2 /day divided BID; Niclosamide 250 mg/m2 /day divided BID; Niclosamide 500 mg/m2 /day divided BID; Niclosamide 800 mg/m2 /day divided BID

Eligibility Criteria

• Age: 2 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• \. Prior morphologically-confirmed diagnosis of AML based on WHO Criteria 2. Has previously failed all available and suitable therapies for AML. Disease relapse or the presence of refractory disease after ≥ 2 cycles of intensive chemotherapy; or ≥ 4 cycles of non-intensive chemotherapy or hypomethylating agents (HMAs) must be documented by bone marrow (BM) examination demonstrating ≥ 5% blasts in the BM by morphology or ≥ 1% blasts by flow cytometry,
• % blasts in the peripheral blood (confirmed by flow cytometry, cytogenetics or FISH), ≥ 1% MRD
• \+ by flow cytometry, FISH, PCR or NGS, and not attributable to another cause (EXCEPTION: subjects with frank disease progression in the face of treatment with HMA with or without venetoclax will be considered eligible regardless of treatment cycles administered if they meet the other eligibility criteria). No prior treatment with niclosamide. 3. Age ≥ 2 and ≤ 30 years 4. Body surface area (BSA) ≤ 2.10 m2
• , calculated per the Mostellar formula 5. Must be able to tolerate po or ng medications. 6. Performance status: Subject ≤ 16 years old: Lansky ≥ 50 Subject \> 16 years old: Karnofsky ≥ 50% 7. Life expectancy of greater than 4 weeks 8. Platelets ≥ 10,000/mm3 (for subjects with platelets \< 10,000/mm3 at baseline, platelet transfusion support is allowed) 9. Measured or calculated creatinine clearance
• mL/min/1.73 m2 (by the Cockcroft-Gault method) within 14 days prior to treatment initiation 10. Total bilirubin ≤ 2.0 x institutional upper limit of normal (ULN) within 14 days prior to treatment initiation (EXCEPTION: Subjects with Gilbert's syndrome may be included if the total bilirubin is
• x ULN) 11. SGOT (AST) ≤ 3.0 x ULN and SGPT (ALT)
• x ULN within 14 days prior to treatment initiation 12. Patients must have received their last dose of anti-cancer therapy (chemotherapy, immunotherapy, targeted agents, radiotherapy or investigational therapy) at least 2 weeks or 3 half-lives prior to the start of study treatment, whichever is longer. 13. For patients who have received prior hematopoietic stem cell transplants (HSCT), no evidence of GvHD and must be \> 60 days since the HSCT. HSCT recipients must have completed their last course of tacrolimus, cyclosporine, or mycophenolate \> 4 weeks before initiation of niclosamide 14. Females of reproductive potential (WOCBP) must have a negative pregnancy test within 14 days prior to study treatment. WOCBP must agree to use adequate contraception (eg, hormonal or barrier methods of birth control; abstinence; sterilized partner) from date of consent through the treatment period, and for 30 days after completion of niclosamide administration 15. Men only: Men must agree to use adequate contraception (eg, hormonal or barrier methods of birth control; abstinence; sterilized partner) from date of consent through the treatment period, and for 30 days after completion of niclosamide administration 16. Ability to understand the purpose and risks of the study and the willingness to sign a written informed consent document containing an authorization to use protected health information (in accordance with national and local subject privacy regulations

You may not qualify if:

• Received anticancer therapy (chemotherapy, immunotherapy, radiotherapy, or investigational therapy) within 2 weeks prior to starting study treatment. Administration of hydroxyurea 10 to 20 mg/kg/day PO (maximum 1000 mg PO BID) to control high WBC \> 50 x 103
• /mm3 is permitted at MD discretion (however, hydroxyurea should be stopped at least 24 hours prior to protocol therapy start).
• Receiving any other investigational agents, including niclosamide.
• Acute promyelocytic leukemia (French-American-British Class M3-AML)
• Known active central nervous system (CNS) leukemia; subjects can enroll on study if CNS disease can be cleared with intrathecal chemotherapy, in the judgement of the treating physician
• Known congenital bleeding disorders, including but not limited to hemophilia
• Known active uncontrolled systemic infection
• 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
• Inability to receive administration of niclosamide in the available formulation(s)
• Uncontrolled intercurrent illness including, but not limited to, uncontrolled active infection, or psychiatric illness/social situations that would limit compliance with study requirements
• Lactating or pregnant female
• Known active hepatitis C

Sponsors & Collaborators

• Stanford University: lead
• The Leukemia and Lymphoma Society: collaborator
• Pediatric Cancer Research Foundation (PCRF): collaborator
• CURE Childhood Cancer, Inc.: collaborator

Study Sites (1)

Stanford University

Palo Alto, California, 94305, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Niclosamide

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Salicylanilides; Anilides; Amides; Organic Chemicals; Salicylamides; Aniline Compounds; Amines

Study Officials

• Kathleen M Sakamoto, MD, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nancy Sweeters

CONTACT

650-724-4042; nks2016@stanford.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2021
• First Posted: January 12, 2022
• Study Start: November 21, 2022
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)