Niclosamide in Pediatric Patients With Relapsed and Refractory AML

Inclusion Criteria:

• Prior morphologically confirmed diagnosis of AML based on WHO Criteria

• Has previously failed all available and suitable therapies for AML Disease relapseor the presence of refractory disease after ≥ 2 cycles of chemotherapy must bedocumented by bone marrow (BM) examination demonstrating > 5% blasts in the BM notattributable 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.

• Age ≥ 2 and ≤ 25 years

• Body surface area (BSA) ≤ 2.10 m2, calculated per the Mostellar formula

• Must be able to tolerate po or ng medications.

• Performance status:

• Subject age

≤ 16 years old: Lansky score ≥ 50 > 16 years old: Karnofsky score ≥ 50%

• Life expectancy of greater than 4 weeks

• Platelets ≥ 10,000/mm3 (for subjects with platelets < 10,000/mm3 at baseline,platelet transfusion support is allowed)

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

• Total bilirubin ≤ 2.0 x Institutional upper limit of normal (ULN) within 14 daysprior to treatment initiation, unless the elevation is due primarily to elevatedunconjugated hyperbilirubinemia secondary to Gilbert's syndrome or hemolysis or nonhepatic origin, and not to liver dysfunction

• SGOT (AST) ≤ 3.0 x ULN and SGPT (ALT) ≤ 3.0 x ULN within 14 days prior to treatmentinitiation

• 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 ofbirth control; abstinence; sterilized partner) for the duration of studyparticipation

• Men only: Men must agree to use adequate contraception (eg, hormonal or barriermethods of birth control; abstinence; sterilized partner) prior to the studytreatment (from date of consent), for the duration of study participation, and 30days after completion of niclosamide administration

• Ability to understand the purpose and risks of the study and the willingness to signa written informed consent document containing an authorization to use protectedhealth information (in accordance with national and local subject privacyregulations

Exclusion Criteria:

• 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 is permitted.

• Receiving any other investigational agents.

• 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

• Acute promyelocytic leukemia (French American British Class M3 AML)

• 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

• Prior bone marrow transplant presenting with active uncontrolled graft versus hostdisease (GvHD)

• 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 inflammatorybowel disease or ulcerative colitis, or partial or complete bowel obstruction, atthe time of study entry

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

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

• Lactating or pregnant female

• Known active hepatitis C