De- Escalation and Stopping Treatment of Imatinib, Nilotinib or sprYcel in Chronic Myeloid Leukaemia

NCT01804985 | Completed Phase 2 DMC

• 1 other identifier: 4203
• Study Type: interventional
• Target: 174
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate whether some patients with excellent responses to chronic myeloid leukaemia (CML) treatment are being overtreated, and can remain well on either a lower dose of treatment or without treatment at all. The dose of imatinib (Glivec), nilotinib (Tasigna) or dasatinib (Sprycel) treatment will initially be cut to half the standard dose for 12 months, and then treatment will be stopped completely for a further two years. The trial information will also help to develop a de-escalation and stopping strategy for future newly diagnosed CML patients in the next British national CML study (to be known as SPIRIT3).

Conditions

Chronic Myeloid Leukaemia

Outcome Measures

Primary Outcomes (1)

• • The proportion of patients who can first de-escalate their treatment (to half the standard dose of their TKI) for 12 months, and then stop treatment completely for a further 2 years, without losing MMR.

  • The proportion of patients who can first de-escalate their treatment (to half the standard dose of their TKI) for 12 months, and then stop treatment completely for a further 2 years, without losing MMR.

  37months

Secondary Outcomes (5)

• • Proportion of patients who can successfully de-escalate their treatment (to half the standard dose of their TKI), but who then lose MMR on complete TKI cessation

  37 months

• • Proportion of patients who lose their MMR on de-escalation/stopping and regain MMR on resumption of their TKI

  37 months

• • Quality of Life

  37 months

• • Health Economic Assessment

  37 months

• • Lab studies to define subsets of patients who are more likely to relapse on de-escalation / cessation.

  37 months

Study Arms (1)

De-escalated Treatment

EXPERIMENTAL

Imatinib, nilotinib or dasatinib; de-escalated to half the standard dose for 12 months

Drug: Imatinib; Drug: nilotinib; Drug: dasatinib

Interventions

Imatinib DRUG

Imatinib, nilotinib or dasatinib; de-escalated to half the standard dose for 12 months. If on imatinib, the dose should be decreased to 200mg daily;

Also known as: Glivec or Gleevec

De-escalated Treatment

nilotinib DRUG

Imatinib, nilotinib or dasatinib; de-escalated to half the standard dose for 12 months. if on nilotinib to 200mg twice daily (which is half the standard dose for second line use, since it is anticipated that the vast majority of nilotinib entrants will be receiving 400mg twice daily because of prior imatinib intolerance);

Also known as: Tasigna

De-escalated Treatment

dasatinib DRUG

Imatinib, nilotinib or dasatinib; de-escalated to half the standard dose for 12 months. If on dasatinib then to 50 mg daily.

Also known as: Sprycel

De-escalated Treatment

Eligibility Criteria

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

You may qualify if:

• CML in first chronic phase.
• Demonstration of BCR-ABL1 positivity at/shortly after original diagnosis.
• Written Informed Consent
• Must have received TKI treatment for at least 3 years.
• At least 3 molecular results over the preceding 12 months, that fit either of the following groups (results from any UK lab are acceptable):
• (MR4 group) all the available BCR-ABL1 molecular results over the preceding 12 months are in MR4 (MR4 is defined as a BCR-ABL1/ABL1 ratio of zero, (reported to International Standards (IS) where possible; with at least 10,000 ABL1 control transcripts).
• (MMR group) some or all BCR-ABL1 molecular results are in major molecular response (MMR), defined here as a BCR-ABL1/ABL1 ratio of 0.1% or less, (reported to International Standard (IS) where possible), but not zero, with at least 10,000 ABL1 control transcripts. If the results over the preceding 12 months are a mix of MMR and undetectable BCR-ABL1, then the patient is eligible for the MMR but not the MR4 group.

You may not qualify if:

• Age under 18
• Life expectancy predicted to be less than 37 months because of intercurrent illness
• Presence of serious concomitant illness (e.g. heart, renal, respiratory or active malignant disease) that might preclude completion of the trial
• CML in accelerated phase or blast crisis at any time
• Any molecular result during the preceding 12 months that is not in either MMR or MR4.
• Patients who switched previous licensed TKI treatment (imatinib, nilotinib or dasatinib) twice or more because of intolerance
• Treatment with higher than standard TKI doses ('standard' is defined as imatinib 400mg daily, nilotinib 400mg twice daily or dasatinib 100mg daily). However, an exception is made for patients who at original diagnosis commenced on either 800mg of imatinib on the SPIRIT1 study, or 140mg (or 70mg b.d) of dasatinib in the Bristol-Myers Squibb 034 study. In each case these latter patients ARE eligible provided they fulfil other molecular criteria, since they do not demonstrate resistant disease.
• Patients who switched previous licensed TKI treatment (imatinib, nilotinib or dasatinib) because of resistance. Patients treated with lower (but at least 50%) than the standard TKI doses (as defined in previous criterion) for tolerance reasons may be included, but will de-escalate to the same doses as for standard dose patients and will be analysed separately, as they could be seen as undertreated.
• Previous treatment with ponatinib or bosutinib. Patients who received interferon prior to commencing TKI (even if resistant to their interferon) are eligible, provided their response to TKI fits the entry criteria.
• Pregnant or lactating women
• Women of childbearing potential (including women whose last menstrual period was less than one year prior to screening) who are unable or unwilling to use adequate contraception from study start to one year after the last dose of protocol therapy. Adequate contraception is defined as hormonal birth control, intrauterine device, double barrier method or total abstinence.

Sponsors & Collaborators

• University of Liverpool: lead
• Newcastle University: collaborator
• Imperial College London: collaborator
• University of Glasgow: collaborator

Study Sites (1)

University of Liveprool

Liverpool, L69 3GL, United Kingdom

Location

Related Publications (2)

• Clark RE, Polydoros F, Apperley JF, Milojkovic D, Rothwell K, Pocock C, Byrne J, de Lavallade H, Osborne W, Robinson L, O'Brien SG, Read L, Foroni L, Copland M. De-escalation of tyrosine kinase inhibitor therapy before complete treatment discontinuation in patients with chronic myeloid leukaemia (DESTINY): a non-randomised, phase 2 trial. Lancet Haematol. 2019 Jul;6(7):e375-e383. doi: 10.1016/S2352-3026(19)30094-8. Epub 2019 Jun 12.

  PMID: 31201085 DERIVED

• Clark RE, Polydoros F, Apperley JF, Milojkovic D, Pocock C, Smith G, Byrne JL, de Lavallade H, O'Brien SG, Coffey T, Foroni L, Copland M. De-escalation of tyrosine kinase inhibitor dose in patients with chronic myeloid leukaemia with stable major molecular response (DESTINY): an interim analysis of a non-randomised, phase 2 trial. Lancet Haematol. 2017 Jul;4(7):e310-e316. doi: 10.1016/S2352-3026(17)30066-2. Epub 2017 May 26.

  PMID: 28566209 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Imatinib Mesylate; nilotinib; Dasatinib

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; Thiazoles; Sulfur Compounds; Azoles

Study Officials

• Richard E Clark, MA MD

  University of Liverpool

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2013
• First Posted: March 5, 2013
• Study Start: December 1, 2013
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: March 14, 2025

Record last verified: 2018-09

Locations

GB (1)