Niclosamide in Pediatric Patients With Relapsed and Refractory AML

Inclusion Criteria:

1. 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,

• 5% blasts in the peripheral blood (confirmed by flow cytometry, cytogenetics orFISH), ≥ 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 withHMA with or without venetoclax will be considered eligible regardless of treatmentcycles administered if they meet the other eligibility criteria). No prior treatmentwith 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 ngmedications. 6. Performance status: Subject ≤ 16 years old: Lansky ≥ 50 Subject > 16years 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, platelettransfusion support is allowed) 9. Measured or calculated creatinine clearance

• 60 mL/min/1.73 m2 (by the Cockcroft-Gault method) within 14 days prior to treatmentinitiation 10. Total bilirubin ≤ 2.0 x institutional upper limit of normal (ULN)within 14 days prior to treatment initiation (EXCEPTION: Subjects with Gilbert'ssyndrome may be included if the total bilirubin is

• 3.0 x ULN) 11. SGOT (AST) ≤ 3.0 x ULN and SGPT (ALT)

• 3.0 x ULN within 14 days prior to treatment initiation 12. Patients must havereceived their last dose of anti-cancer therapy (chemotherapy, immunotherapy,targeted agents, radiotherapy or investigational therapy) at least 2 weeks or 3half-lives prior to the start of study treatment, whichever is longer. 13. Forpatients who have received prior hematopoietic stem cell transplants (HSCT), noevidence of GvHD and must be > 60 days since the HSCT. HSCT recipients musthave completed their last course of tacrolimus, cyclosporine, or mycophenolate > 4 weeks before initiation of niclosamide 14. Females of reproductivepotential (WOCBP) must have a negative pregnancy test within 14 days prior tostudy treatment. WOCBP must agree to use adequate contraception (eg, hormonalor barrier methods of birth control; abstinence; sterilized partner) from dateof consent through the treatment period, and for 30 days after completion ofniclosamide administration 15. Men only: Men must agree to use adequatecontraception (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 tounderstand the purpose and risks of the study and the willingness to sign awritten informed consent document containing an authorization to use protectedhealth information (in accordance with national and local subject privacyregulations

Exclusion Criteria:

1. Received anticancer therapy (chemotherapy, immunotherapy, radiotherapy, orinvestigational therapy) within 2 weeks prior to starting study treatment.Administration of hydroxyurea 10 to 20 mg/kg/day PO (maximum 1000 mg PO BID) tocontrol 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).

2. Receiving any other investigational agents, including niclosamide.

3. Unresolved toxicities due to prior anticancer therapy, defined as not havingresolved to Grade 0 or 1 (by CTCAE version 5 criteria), unless otherwise defined inthe inclusion/exclusion criteria with the exception of alopecia

4. Acute promyelocytic leukemia (French-American-British Class M3-AML)

5. Known active central nervous system (CNS) leukemia; subjects can enroll on study ifCNS disease can be cleared with intrathecal chemotherapy, in the judgement of thetreating physician

6. Known congenital bleeding disorders, including but not limited to hemophilia

7. Known active uncontrolled systemic infection

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

9. Inability to receive administration of niclosamide in the available formulation(s)

10. Uncontrolled intercurrent illness including, but not limited to, uncontrolled activeinfection, or psychiatric illness/social situations that would limit compliance withstudy requirements

11. Lactating or pregnant female

12. Known active hepatitis C