Acute Myeloid Leukemia (AML)
Conditions
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.
Interventions
DRUGNiclosamide
Niclosamide will be administered orally for 14 days. Each dose will be followed by backbone chemotherapy
Sponsors
The Leukemia and Lymphoma Society
Pediatric Cancer Research Foundation (PCRF)
CURE Childhood Cancer, Inc.
Stanford University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 25 Years
Healthy volunteers
No
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 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 * 60 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 * 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 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
Exclusion criteria
1. 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). 2. Receiving any other investigational agents, including niclosamide. 3. Unresolved toxicities due to prior anticancer therapy, defined as not having resolved to Grade 0 or 1 (by CTCAE version 5 criteria), unless otherwise defined in the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting toxicity | 30 days | Dose-limiting toxicities (DLTs) are defined as any events ≥ Grade 3 that are at least possibly, probably, or definitely related to niclosamide treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of niclosamide treatment clinical response | 8 weeks | Clinical response is defined as any of the following. * Complete response (CR) = \< 5% blasts in BM, with no evidence of extramedullary disease. * Partial response (PR) = ≥ 5% to ≤ 25% blasts in BM with decrease in BM blast percentage by 50%, and no evidence of extramedullary disease. * Resistant disease with clinical benefit (RD-CB) = either ≥ 5% to ≤ 25% blasts in BM OR a decrease in blast percentage by 50%, either with no evidence of extramedullary disease. No response (NR) is defined as BM disease that does not fall into the above categories |
Countries
United States
Contacts
Primary ContactNancy Sweeters
Outcome results
None listed