Niclosamide in Pediatric Patients With Relapsed and Refractory AML

Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age2-25
SponsorStanford University

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

5% blasts in the peripheral blood (confirmed by flow cytometry, cytogenetics or FISH), ≥ 1% MRD

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

Disqualifiers

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

Receiving any other investigational agents, including niclosamide.

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/exclusion criteria with the exception of alopecia

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

Trial design

Design model

Sequential

Treatments tested in this trial

  • Niclosamide

    Drug

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

Treatment groups

16 Participants
are divided into 4 treatment groups
Group A: Niclosamide 250 mg/m2 /day divided BIDExperimental treatment 1 intervention
Group B: Niclosamide 500 mg/m2 /day divided BIDExperimental treatment 1 intervention
Group C: Niclosamide 800 mg/m2 /day divided BIDExperimental treatment 1 intervention
Group D: Niclosamide 1200 mg/m2 /day divided BIDExperimental treatment 1 intervention

Trial outcomes

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

Time frame
30 days

Secondary outcomes

1

Efficacy of niclosamide treatment clinical response

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

Time frame
8 weeks

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Stanford University

Lead sponsor

The Leukemia and Lymphoma Society

Collaborator

Pediatric Cancer Research Foundation (PCRF)

Collaborator

CURE Childhood Cancer, Inc.

Collaborator