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The Analysis of Fatigue on Tyrosine Kinase Inhibitor Therapy in Chronic Myeloid Leukaemia

NCT ID: NCT06233890

Last Updated: 2024-01-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Total Enrollment

50 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-05-12

Study Completion Date

2026-05-12

Brief Summary

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The goal of this clinical study is to gain essential insights into the relationship between Tyrosine kinase inhibitor (TKI) therapy and profound fatigue and abnormal sleep patterns using rest-activity monitoring (actigraphy) and peripheral blood biomarkers in patients with Chronic myeloid leukaemia in chronic phase. The main aims are to

1. Determine the variance of subjective and objective sleep disturbance
2. Determine the difference in serum biomarkers (activin B and L-carnitine)
3. Determine how thes findings concord/discord between treatment and control groups.

Participants will asked to undergo 2 weeks of actigraphy monitoring and keep a sleep diary during this time. Blood and urine samples will be taken for analysis.

Researchers will compare two groups (patients with fatigue and those without) to assess the differences between groups.

Detailed Description

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The therapeutic landscape of CML has evolved significantly, as a result of targeted TKI therapy, over the past 2 decades with patients now experiencing a near normal life expectancy due to achievement of deep molecular responses. As a consequence, the appropriate management of drug related adverse events to ensure minimal impact on quality of life has never been more vital. Fatigue and sleep disturbance are commonly described and whilst it is evident that there is a strong correlation between fatigue and TKI therapy, the mechanism which drives this remains unknown. In general, the prevalence of TKI induced fatigue and predicting factors is largely unexplored. This exploratory, pilot study aims to examine the rest-activity patterns, blood parameters and fatigue related serum biomarkers of CML patients affected by fatigue on TKI therapy, and aims to provide insight into the association between fatigue and sleep disturbance on treatment. The pilot study aims to recruit 25 patients with profound fatigue on TKI therapy, for a minimum of 6 months with an impact on their activities of daily living. Additionally, we will recruit 25 further patients (age, gender and TKI matched) as a control cohort, who also have a diagnosis of Chronic Phase CML with no symptoms of fatigue. Validated fatigue questionnaires will be used (Chalder fatigue scale and the Fisk fatigue impact scale), these are key diagnostic tools in Fatigue associated disorders. TKI- fatigue syndrome (TKI-FS) symptoms can emulate the clinical pattern of Chronic Fatigue Syndrome (CFS) and this project would delineate congruence between CFS and TKI-FS. The patient cohort will also undergo actigraphy, this will be used in this study as a validated objective sleep measure, this method uses sophisticated analysis of movement to infer sleep/wake patterns. Actigraphy is non-invasive and can be used for several weeks, alongside a daily sleep diary, allowing collection of naturalistic sleep data as a participant goes about their normal activities. In addition, serum biomarkers such as activin B is a member of the activin family of proteins, which belongs to the TGF-β superfamily of growth and differentiation factors; activin B has been shown to be a potential serum biomarker in fatigue related disorders. In addition, L-carnitine is a vital molecular component in many metabolic pathways, the majority of the total body carnitine is located within skeletal muscle. Impairments in L-carnitine synthesis, transport or metabolism can result in primary or secondary deficiencies, which ultimately results in muscle weakness and fatigue. Assessment of both of these serum biomarkers in both the fatigue and control cohort may shed insight on whether there are significant differences between those patients with TKI-FS and the control group.

The aim of the study is to use the above stated modalities in order to gain further insight into the association between fatigue and sleep disturbance in CML patients treated with TKI therapy, which can have a debilitating impact on patients.

Conditions

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Chronic Myeloid Leukemia Chronic Myeloid Leukemia, Chronic Phase Fatigue Sleep Disturbance

Keywords

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Tyrosine kinase inhibitor chronic myeloid leukaemia sleep disturbance fatigue Activin B L-carnitine

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Fatigue

Group 1: Fatigue present for more than 6 months with impairment in daily life activities.

Fatigue will be assessed using two validated fatigue questionnaires completed at the screening visit. The Chalder fatigue scale (CFQ) is an 11 item scale which assesses the severity of fatigue over the last 90 days and the Modified Fatigue Impact scale (MFIS), commonly used to determine the impact of fatigue on quality of life, assesses fatigue over the previous 30 days. Both scales are diagnostic tools in chronic disease associated fatigue. Scores on these scales will determine if patients are eligible. For this group a score \> or = 5 for Chalder score and \> or = 43 for the MFIS score.

Motion watch

Intervention Type DEVICE

Actigraphy watch to be worn for 14 days

Non -Fatigue

Group 2: no significant symptoms of fatigue on TKI therapy. Fatigue will be assessed using two validated fatigue questionnaires completed at the screening visit. The Chalder fatigue scale (CFQ) is an 11 item scale which assesses the severity of fatigue over the last 90 days and the Modified Fatigue Impact scale (MFIS), commonly used to determine the impact of fatigue on quality of life, assesses fatigue over the previous 30 days. Both scales are diagnostic tools in chronic disease associated fatigue. Scores on these scales will determine if patients are eligible. For this group a score \< or = 2 for Chalder score and \< or = 33 for the MFIS score.

Motion watch

Intervention Type DEVICE

Actigraphy watch to be worn for 14 days

Interventions

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Motion watch

Actigraphy watch to be worn for 14 days

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

1. Informed consent
2. Diagnosis of CML on treatment with tyrosine kinase inhibitor.
3. On stable TKI therapy for at least 6 months duration
4. Confirmation of ongoing chronic phase
5. Male or females aged: 18 - 70 years old
6. On-going fatigue for more than 6 months with impairment in daily life activities/ or no fatigue as described in point 7.
7. If recruited to fatigue group then subjects would require both a - Chalder score \> or = 5 and a Modified Fatigue Impact scale score \> or = 43
8. If recruited to control group, then subjects would require both a Chalder score \< or = 2 and a Modified Fatigue Impact Scale score \<33

Exclusion Criteria

1. Not currently on treatment with a TKI inhibitor.
2. Previous or active other neoplasm.
3. Past medical history including diagnosed sleep disorder, depression and on current therapy, sleep apnoea, uncontrolled thyroid dysfunction and neurological disorder
4. Active treatment with any of the following drug groups: anti cholinergic or anti muscarinic drugs, tricyclic antidepressants, serotonin norepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors (SSRIs), Norepinephrine Dopamine Reuptake inhibitor (NDRI), Serotonin antagonist and reuptake inhibitor (SARI), Norepinephrine Antagonist serotonin antagonist (NASA), Monoamine oxidase inhibitors (MAO), regular sedating antihistamine use, regular opioid use, beta blockers, methyldopa, clonidine, benzodiazepines and zopiclone.
5. Prior allogeneic SCT
6. Have a history of alcohol or substance abuse
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Imperial College Healthcare NHS Trust

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Dragana Milojkovic, MbChB, PHD

Role: PRINCIPAL_INVESTIGATOR

Imperial NHS Healthcare Trust

Locations

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Imperial NHS Healthcare Trust

London, , United Kingdom

Site Status

Countries

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United Kingdom

References

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Innes AJ, Milojkovic D, Apperley JF. Allogeneic transplantation for CML in the TKI era: striking the right balance. Nat Rev Clin Oncol. 2016 Feb;13(2):79-91. doi: 10.1038/nrclinonc.2015.193. Epub 2015 Nov 17.

Reference Type RESULT
PMID: 26573423 (View on PubMed)

Efficace F, Baccarani M, Breccia M, Alimena G, Rosti G, Cottone F, Deliliers GL, Barate C, Rossi AR, Fioritoni G, Luciano L, Turri D, Martino B, Di Raimondo F, Dabusti M, Bergamaschi M, Leoni P, Simula MP, Levato L, Ulisciani S, Veneri D, Sica S, Rambaldi A, Vignetti M, Mandelli F; GIMEMA. Health-related quality of life in chronic myeloid leukemia patients receiving long-term therapy with imatinib compared with the general population. Blood. 2011 Oct 27;118(17):4554-60. doi: 10.1182/blood-2011-04-347575. Epub 2011 Jul 12.

Reference Type RESULT
PMID: 21750313 (View on PubMed)

Lidbury BA, Kita B, Lewis DP, Hayward S, Ludlow H, Hedger MP, de Kretser DM. Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study. J Transl Med. 2017 Mar 16;15(1):60. doi: 10.1186/s12967-017-1161-4.

Reference Type RESULT
PMID: 28302133 (View on PubMed)

Cruciani RA, Zhang JJ, Manola J, Cella D, Ansari B, Fisch MJ. L-carnitine supplementation for the management of fatigue in patients with cancer: an eastern cooperative oncology group phase III, randomized, double-blind, placebo-controlled trial. J Clin Oncol. 2012 Nov 1;30(31):3864-9. doi: 10.1200/JCO.2011.40.2180. Epub 2012 Sep 17.

Reference Type RESULT
PMID: 22987089 (View on PubMed)

Bower H, Bjorkholm M, Dickman PW, Hoglund M, Lambert PC, Andersson TM. Life Expectancy of Patients With Chronic Myeloid Leukemia Approaches the Life Expectancy of the General Population. J Clin Oncol. 2016 Aug 20;34(24):2851-7. doi: 10.1200/JCO.2015.66.2866. Epub 2016 Jun 20.

Reference Type RESULT
PMID: 27325849 (View on PubMed)

Sadeh A. The role and validity of actigraphy in sleep medicine: an update. Sleep Med Rev. 2011 Aug;15(4):259-67. doi: 10.1016/j.smrv.2010.10.001. Epub 2011 Jan 14.

Reference Type RESULT
PMID: 21237680 (View on PubMed)

Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193-213. doi: 10.1016/0165-1781(89)90047-4.

Reference Type RESULT
PMID: 2748771 (View on PubMed)

Sharf G, Marin C, Bradley JA, Pemberton-Whiteley Z, Bombaci F, Christensen RIO, Gouimi B, Deekes NB, Daban M, Geissler J. Treatment-free remission in chronic myeloid leukemia: the patient perspective and areas of unmet needs. Leukemia. 2020 Aug;34(8):2102-2112. doi: 10.1038/s41375-020-0867-0. Epub 2020 May 26.

Reference Type RESULT
PMID: 32457354 (View on PubMed)

Luik AI, Zuurbier LA, Hofman A, Van Someren EJ, Tiemeier H. Stability and fragmentation of the activity rhythm across the sleep-wake cycle: the importance of age, lifestyle, and mental health. Chronobiol Int. 2013 Dec;30(10):1223-30. doi: 10.3109/07420528.2013.813528. Epub 2013 Aug 23.

Reference Type RESULT
PMID: 23971909 (View on PubMed)

Other Identifiers

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22HH7973

Identifier Type: -

Identifier Source: org_study_id