Improving Treatment Outcomes in Chronic Myeloid Leukaemia Patients Using Imatinib and Artesunate Combination Therapy

Summary

Chronic myeloid leukaemia (CML) is a blood cancer with an annual worldwide incidence of 1/100,000 population. Imatinib is used for the treatment of CML and has significantly improved the management of the disease. However, the incidence of treatment failure due to imatinib resistance has become a considerable burden (Sherbenou et al., 2007). Artesunate, an antimalarial drug, is reported to have anti-neoplastic effect either singly or in synergy with already established anti-neoplastic agents (Krishna et al., 2015). The aim of the study is to evaluate the clinical effectiveness of an Imatinib-artesunate combination compared to imatinib alone and its possibility as an alternative option in the management of sub-optimal response in CML patients especially in low- and middle- income country like Nigeria where second line tyrosine kinase inhibitor may be out of reach. The specific objectives are to: 1. Assess the safety of artesunate use beyond its traditional antimalarial dosing period in CML patients. 2. Compare treatment outcomes between patients on imatinib alone and patients on imatinib plus artesunate at 3, 6 and 12-months of follow-up. 3. Determine the effect of imatinib and artesunate combination on the achievement of major molecular remission in CML patients with sub-optimal response to imatinib. 4. Determine the effect of artesunate on imatinib pharmacokinetics following co-administration of the two drugs. The main questions it aims to answer is: * Does the use of artesunate in combination with imatinib in newly diagnosed CML patient give a better therapeutic outcome than using imatinib alone? * Does combining artesunate with imatinib in CML patients with sub-optimal response to imatinib improve patients' response to imatinib? * Does combining artesunate with imatinib in CML patients affect the pharmacokinetic parameter of imatinib? * Is it safe to take artesunate at 4mg/day (not exceeding 200mg/day) for a 14day cycle in CML patients as demonstrated in other forms of cancer? Participants will be assigned to one of the groups of the study and continue imatinib medication irrespective of the group assigned and come to clinic once a month for follow-up. Clinic visits will be immediately after a cycle of artesunate for groups B and C.

Timeline

Start

2025-07-01

Primary completion

2026-07

Completion

2026-12

Publications

• Background Bethell D, Se Y, Lon C, Socheat D, Saunders D, Teja-Isavadharm P, Khemawoot P, Darapiseth S, Lin J, Sriwichai S, Kuntawungin W, Surasri S, Lee SJ, Sarim S, Tyner S, Smith B, Fukuda MM. Dose-dependent risk of neutropenia after 7-day courses of artesunate monotherapy in Cambodian patients with acute Plasmodium falciparum malaria. Clin Infect Dis. 2010 Dec 15;51(12):e105-14. doi: 10.1086/657402. Epub 2010 Nov 11.
• Background Krishna S, Ganapathi S, Ster IC, Saeed ME, Cowan M, Finlayson C, Kovacsevics H, Jansen H, Kremsner PG, Efferth T, Kumar D. A Randomised, Double Blind, Placebo-Controlled Pilot Study of Oral Artesunate Therapy for Colorectal Cancer. EBioMedicine. 2014 Nov 15;2(1):82-90. doi: 10.1016/j.ebiom.2014.11.010. eCollection 2015 Jan.
• Background White WL. Erratum to: Why I hate the index finger. Hand (N Y). 2011 Jun;6(2):233. doi: 10.1007/s11552-011-9321-0. Epub 2011 Mar 18.
• Background Kim C, Lee JH, Kim SH, Sethi G, Ahn KS. Artesunate suppresses tumor growth and induces apoptosis through the modulation of multiple oncogenic cascades in a chronic myeloid leukemia xenograft mouse model. Oncotarget. 2015 Feb 28;6(6):4020-35. doi: 10.18632/oncotarget.3004.
• Background Mander AP, Thompson SG. Two-stage designs optimal under the alternative hypothesis for phase II cancer clinical trials. Contemp Clin Trials. 2010 Nov;31(6):572-8. doi: 10.1016/j.cct.2010.07.008. Epub 2010 Aug 1.
• Background Smith G, Apperley J, Milojkovic D, Cross NCP, Foroni L, Byrne J, Goringe A, Rao A, Khorashad J, de Lavallade H, Mead AJ, Osborne W, Plummer C, Jones G, Copland M; British Society for Haematology. A British Society for Haematology Guideline on the diagnosis and management of chronic myeloid leukaemia. Br J Haematol. 2020 Oct;191(2):171-193. doi: 10.1111/bjh.16971. Epub 2020 Jul 30. No abstract available.
• Background Oyekunle AA, Bolarinwa RA, Oyelese AT, Salawu L, Durosinmi MA. Determinants of Overall and Progression-Free Survival of Nigerian Patients with Philadelphia-Positive Chronic Myeloid Leukemia. Adv Hematol. 2015;2015:908708. doi: 10.1155/2015/908708. Epub 2015 Sep 7.
• Background Morotti A, Fava C, Saglio G. Milestones and monitoring. Curr Hematol Malig Rep. 2015 Jun;10(2):167-72. doi: 10.1007/s11899-015-0258-1.

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