Tyrosine Kinase Inhibitor Withdrawal Syndrome in CML Patients: Observatory Trial Studying the Biological Factors.

NCT03996096 | Completed

• 1 other identifier: 18-206
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Patients who suffer from chronic myeloid leukemia are treated by tyrosin kinase inhibitors (TKI) saying imatinib, nilotinib, dasatinib, bosutinib and ponatinib. These drugs are highly efficient with excellent response allowing some patients to definitely stop their cancer treatment. However, in 30% of cases, when the treatment is stopped, pains could arise in shoulders, hips, joints… These symptoms occurring after the withdrawal of a drug are odd and biologically unexplained so far. This study seeks to discover the biological factors behind these symptoms called 'TKI withdrawal syndrome' by the scientific community.

Conditions

Chronic Myeloid Leukemia; Tyrosine Kinase Inhibitor; Withdrawal Syndrome

Outcome Measures

Primary Outcomes (11)

• Measurement of cytokines:

  Measurement of cytokines: A variation of 20% in a given marker will be significant if it is observed in the group with "TKI WS" but not in the group without "TKI WS". Of note, the patient will be his own witness. . In picogram/milliliter (pg/ml): IL2,IL 6, IL10, IL15, TGFβ,TNFα, IFNγ, VEGF, PDGFβ,

  at diagnosis and every month during 3 months

• Measurement of cytokines:

  In nanogram/milliliter (ng/ml) : Osteoprotegerin

  at diagnosis and every month during 3 months

• Measurement of cytokines:

  • In microgram/liter (µg/l): Tryptase

  at diagnosis and every month during 3 months

• Inflammatory markers:

  C reactive protein (milligramme/liter)

  at diagnosis and every month during 3 months

• Inflammatory markers:

  In international Unit/ liter (IU/l) Rheumatoid factor,

  at diagnosis and every month during 3 months

• Inflammatory markers:

  In international Unit/ liter (IU/l) Creatinine phosphokinase

  at diagnosis and every month during 3 months

• bone metabolism markers

  In microgram/ liter : Cross-laps

  at diagnosis and every month during 3 months.

• bone metabolism markers

  In microgram/ liter : Procollagen 1

  at diagnosis and every month during 3 months.

• bone metabolism markers

  PTH (ParaTHormon) (nanogram/Liter)

  at diagnosis and every month during 3 months.

• bone metabolism markers

  In millimole/Liter: Phosphates

  at diagnosis and every month during 3 months.

• bone metabolism markers

  In millimole/Liter: Calcium.

  at diagnosis and every month during 3 months.

Secondary Outcomes (3)

• Brief Pain Inventory (BPI) questionnaire

  12 months

• QDSA questionnaire

  12 months

• QLQ C-30 questionnaire

  12 months

Study Arms (2)

Group with the TKI withdrawal syndrome

There is no intervention. Patients will stop their tyrosine kinase inhibitor yielding to 2 subsets: patients with or without the TKI withdrawal syndrome.

Group without the TKI withdrawal syndrome

As abovementioned.

Eligibility Criteria

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

Study Population

This study concerns patients suffering from Chronic myeloid leukemia treated with TKI (Imatinib, Nilotinib, dasatinib, bosutinib or Ponatinib) for at least 5 years with deep molecular response (MR4) for at least 2 years who agree to stop their drug. Other situation of TKI discontinuation. Five cities are participating in the study: CHU de Caen, CHU d'Amiens, CHU de Clermont-Ferrand, Centre Henri Becquerel de Rouen et le CH de Valenciennes.

You may qualify if:

• Adult CML patient candidate for TKI discontinuation.
• Performans status : 0-2
• Patient provided with information

You may not qualify if:

• Patient unable to fulfill the questionnaires
• Patient suffering from demantia
• Patient treated with any cytokine antagonist

Sponsors & Collaborators

• University Hospital, Caen: lead

Study Sites (1)

University hospital

Caen, 14033, France

Location

Related Publications (4)

• Mahon FX, Rea D, Guilhot J, Guilhot F, Huguet F, Nicolini F, Legros L, Charbonnier A, Guerci A, Varet B, Etienne G, Reiffers J, Rousselot P; Intergroupe Francais des Leucemies Myeloides Chroniques. Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol. 2010 Nov;11(11):1029-35. doi: 10.1016/S1470-2045(10)70233-3. Epub 2010 Oct 19.

  PMID: 20965785 BACKGROUND

• Rousselot P, Charbonnier A, Cony-Makhoul P, Agape P, Nicolini FE, Varet B, Gardembas M, Etienne G, Rea D, Roy L, Escoffre-Barbe M, Guerci-Bresler A, Tulliez M, Prost S, Spentchian M, Cayuela JM, Reiffers J, Chomel JC, Turhan A, Guilhot J, Guilhot F, Mahon FX. Loss of major molecular response as a trigger for restarting tyrosine kinase inhibitor therapy in patients with chronic-phase chronic myelogenous leukemia who have stopped imatinib after durable undetectable disease. J Clin Oncol. 2014 Feb 10;32(5):424-30. doi: 10.1200/JCO.2012.48.5797. Epub 2013 Dec 9.

  PMID: 24323036 BACKGROUND

• Richter J, Soderlund S, Lubking A, Dreimane A, Lotfi K, Markevarn B, Sjalander A, Saussele S, Olsson-Stromberg U, Stenke L. Musculoskeletal pain in patients with chronic myeloid leukemia after discontinuation of imatinib: a tyrosine kinase inhibitor withdrawal syndrome? J Clin Oncol. 2014 Sep 1;32(25):2821-3. doi: 10.1200/JCO.2014.55.6910. Epub 2014 Jul 28. No abstract available.

  PMID: 25071107 BACKGROUND

• Galimberti S, Fontanelli G, Barsotti S, Ricci F, Guerrini F, Barate C. Increased values of the circulating PDGFbeta sustains the "withdrawal syndrome" after tyrosine kinase inhibitor discontinuation in patients affected by chronic myeloid leukemia. Blood Cells Mol Dis. 2015 Oct;55(3):211-2. doi: 10.1016/j.bcmd.2015.06.010. Epub 2015 Jun 23. No abstract available.

  PMID: 26227847 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma samples, if not used, will be kept frozen for further exploration if necessary. An amendment is produced and approved by ethics commitee in 2021/03/03. It relates to the KIR genes polymorphism and HLA class study in Caen patients in whom NK cell phenotype is available.

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Substance Withdrawal Syndrome

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; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• Hyacinthe JOHNSON-ANSAH, Dr

  UNIVERSITY HOSPITAL of CAEN

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 23, 2019
• First Posted: June 24, 2019
• Study Start: April 23, 2019
• Primary Completion: March 16, 2023
• Study Completion: March 16, 2023
• Last Updated: February 14, 2024

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)