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

NCT07022743 | Active Not Recruiting Phase 2

• 2 other identifiers: IMART TrialIRB/IEC/Z0004553
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief 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:

• 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.

Conditions

Chronic Myeloid Leukemia (CML)

Keywords

IMART Trial; Imatinib and artesunate; Chronic myeloid leukemia

Outcome Measures

Primary Outcomes (1)

• Major molecular remission

  The primary endpoint will be the achievement of Major Molecular remission (MMR/MR3) with bcr/abl-1 gene transcript ≤0.1 and deep molecular response (MR4) with bcr/abl-1 gene transcript ≤0.01 at 12 months.

  12 months

Secondary Outcomes (3)

• Plasma Imatinib levels

  3 months, 6 months and 12 months

• Disease progression

  3 months, 6 months, 12 months

• Adverse events relating to long-term use of artesunate

  Accessed after each cycle every month through the 12 months follow-up

Study Arms (3)

Group A: Imatinib alone in newly diagnosed CML patients

ACTIVE COMPARATOR

Imatinib (Glivec) at a dose of 400mg to newly diagnosed CML patients

Drug: Imatinib

Group B: Imatinib and artesunate combination therapy

EXPERIMENTAL

Imatinib (Glivec) at a dose of 400mg daily and artesunate at a dose of 4mg/kg (not exceeding 200mg) daily in newly diagnosed CML patients

Drug: Imatinib; Drug: Artesunate

Group C: Imatinib and artesunate in CML patients

EXPERIMENTAL

Imatinib (Glivec) 400mg and artesunate 400mg in CML patients with documented sub-optimal response to Imatinib, patients will be monitored monthly and reviewed after 3 months

Drug: Imatinib; Drug: Artesunate

Interventions

Imatinib DRUG

Imatinib is a first-line tyrosine kinase inhibitor which is used in the management of chronic myeloid leukaemia. It will be used by all the patients in the 3 arms of the study (Groups A, B and C)

Also known as: Glivec

Group A: Imatinib alone in newly diagnosed CML patients; Group B: Imatinib and artesunate combination therapy; Group C: Imatinib and artesunate in CML patients

Artesunate DRUG

Artesunate has been established to reverse resistance to some chemotherapeutic agents. patients in 2 arms of the study (Groups B and C) will be given artesunate at 4mg/kg (not exceeding 200mg daily) in combination with imatinib

Also known as: Tab Artesunate 50mg

Group B: Imatinib and artesunate combination therapy; Group C: Imatinib and artesunate in CML patients

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed chronic phase CML patients
• Patients with sub-optimal response to imatinib therapy
• Ages between 18 years and 85 years with written informed consent

You may not qualify if:

• Patients with documented hypersensitivity to artesunate
• Patients with cardiovascular disease, pregnancy and inability to give consent will be excluded.
• Patients currently on any medication(s) that may interact with imatinib or affect its pharmacokinetics parameters (like rifampicin and ketoconazole) will be excluded.

Sponsors & Collaborators

• Obafemi Awolowo University: lead

Study Sites (1)

Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife

Ile-Ife, Osun State, 3408, Nigeria

Location

Related Publications (8)

• 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.

  PMID: 21070142 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.

  PMID: 26137537 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.

  PMID: 21776199 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.

  PMID: 25738364 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.

  PMID: 20678585 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.

  PMID: 32734668 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.

  PMID: 26435715 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.

  PMID: 25921389 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Imatinib Mesylate; Artesunate

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Sesquiterpenes; Terpenes

Study Officials

• Prof. R. A. Bolarinwa

  Obafemi Awolowo University, Ile-Ife

  STUDY DIRECTOR

• Dr. B. A. Adeagbo

  Obafemi Awolowo University, Ile-Ife

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Mrs.

Model Details: Group A: Imatinib naive patients placed on Imatinib alone Group B: Imatinib naive patients placed on Imatinib and artesunate Group C: Patients with sub-optimal response to imatinib placed on Imatinib and artesunate

Study Record Dates

• First Submitted: June 7, 2025
• First Posted: June 15, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: September 5, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

NG (1)