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

NCT06233890 | Active Not Recruiting

• 1 other identifier: 22HH7973
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (7)

• Fatigue

  Assessed by validated questionnaires (Chalder and Modified Fatigue Impact scale), with scoring as described in eligibility criteria. Control group \< or = 2 for Chalder score and \< or = 33 for the MFIS score.For fatigue group a score \> or = 5 for Chalder score and \> or = 43 for the MFIS score.

  14 days

• Subjective sleep disturbance

  Assessed by Pittsburgh Sleep Quality Index (validated). Scores for each question range from 0 to 3, with higher scores indicating more acute sleep disturbances. The global PSQI score is then calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, where lower scores denote a healthier sleep quality.

  1 day

• Subjective sleep

  Assessed by sleep diary.

  14 days

• Percentage Sleep Efficiency

  Percentage Sleep efficiency assessed using actigraphy accelerometer that can reliably translate physical motion and exerted energy into a numeric representation measured in 30 or 60-second epochs allowing continuous data collection over weeks. Percentage sleep efficiency is assessed, defined as the ratio between the total sleep time, and the total time dedicated to sleep (both sleeping and awake eg attempting to fall asleep or back asleep), measured in hours and minutes.

  14 days

• Sleep fragmentation index

  Calculated by actigraphy using the total number of awakenings from deeper non-rapid eye movement to lighter sleep divided by the total sleep time in hours. Measured in hours and minutes.

  14 days

• Actigraphy variables

  total sleep time (assumed sleep) measured using muscle motion/movement by accelerator in actigraphy monitor, and using algorithms that transform the raw accelerometer data into counts.

  14 days

• Actual wake time (wake after sleep onset)

  Measured using accelerator in actigraphy monitor to assess objectively time to waking, measured in minutes and hours.

  14 days

Secondary Outcomes (2)

• Serum biomarker analysis

  1 day

• Serum biomarker analysis

  1 day

Study Arms (2)

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.

Device: Motion watch

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.

Device: Motion watch

Interventions

Motion watch DEVICE

Actigraphy watch to be worn for 14 days

Fatigue; Non -Fatigue

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

CML- Chronic phase patients in a single centre with significant fatigue on TKIs in group 1. In Group 2, CML chronic phase patients with no significant fatigue.

You may qualify if:

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

You may not qualify if:

• Not currently on treatment with a TKI inhibitor.
• Previous or active other neoplasm.
• Past medical history including diagnosed sleep disorder, depression and on current therapy, sleep apnoea, uncontrolled thyroid dysfunction and neurological disorder
• 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.
• Prior allogeneic SCT
• Have a history of alcohol or substance abuse

Sponsors & Collaborators

• Imperial College Healthcare NHS Trust: lead

Study Sites (1)

Imperial NHS Healthcare Trust

London, W12 0HS, United Kingdom

Location

Related Publications (9)

• 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.

  PMID: 26573423 RESULT

• 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.

  PMID: 21750313 RESULT

• 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.

  PMID: 28302133 RESULT

• 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.

  PMID: 22987089 RESULT

• 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.

  PMID: 27325849 RESULT

• 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.

  PMID: 21237680 RESULT

• 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.

  PMID: 2748771 RESULT

• 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.

  PMID: 32457354 RESULT

• 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.

  PMID: 23971909 RESULT

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase; Fatigue; Parasomnias

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; Signs and Symptoms; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Study Officials

• Dragana Milojkovic, MbChB, PHD

  Imperial NHS Healthcare Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2024
• First Posted: January 31, 2024
• Study Start: May 12, 2023
• Primary Completion: May 12, 2025
• Study Completion (Estimated): May 12, 2026
• Last Updated: January 31, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)