De-escalation and stopping treatment of imatinib, nilotinib or sprycel in chronic myeloid leukaemia

Phase 2

Completed

• Conditions: Topic: National Cancer Research Network; Subtopic: Haematological Oncology; Disease: Leukaemia (chronic); Cancer; Chronic myelogenous leukaemia

• Registration Number: ISRCTN74084226
• Lead Sponsor: niversity of Liverpool (UK)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-06-12
• Last Update Posted: 3 July 2017

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 168

Inclusion Criteria

1. CML in first chronic phase
2. Demonstration of BCR-ABL1 positivity at or shortly after original diagnosis*
3. Written informed consent
4. Must have received TKI treatment for at least 3 years
5. At least 3 molecular results over the preceding 12 months, that fit either of the following groups (results from any UK lab are acceptable):
5.1. (MR4 group) all the available BCR-ABL1 molecular results over the preceding 12 months are in MR4 (MR4 is defined as a BCRABL1/ABL1 ratio of zero, with at least 10,000 ABL1 control transcripts)
5.2. (MMR group) some or all BCR-ABL1 molecular results are in MMR (BCRABL1/ ABL1 ratio of 0.1% or less, 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.
*Patients who are Philadelphia chromosome (Ph) negative (or whose Ph status is not known) are eligible. Patients who do not have a standard BCR-ABL1 fusion transcript (i.e. other than e13a2 or e14a2, also known as b2a2 and b3a2) are eligible, but before screening the patient, contact should be made with Prof Foroni at Imperial College (see contacts) since specialised quantitative molecular assessment will be required.
Target Gender: Male & Female; Lower Age Limit 18 years

Exclusion Criteria

1. Age under 18
2. Life expectancy is predicted to be less than 37 months because of intercurrent illness
3. Presence of serious concomitant illness (e.g. heart, renal, respiratory or active malignant disease) that might preclude completion of the study
4. CML in accelerated phase or blast crisis at any time
5. Any molecular result during the preceding 12 months that is not in either MMR or MR4
6. Treatment with higher than standard TKI doses (?standard? is defined as imatinib 400mg daily, nilotinib 400mg twice daily or dasatinib 100mg daily)
7. Patients who switched previous licensed TKI treatment (imatinib, nilotinib or dasatinib) twice or more because of intolerance
8. Patients who switched previous licensed TKI treatment (imatinib, nilotinib or dasatinib) because of resistance
9. Patients treated with lower than standard TKI doses (imatinib 400mg daily, nilotinib 400mg twice daily or dasatinib 100mg daily) 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
10. 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.
11. Pregnant or lactating women
12. Women of childbearing potential, including women whose last menstrual period was less than one year prior to screening, 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

Study & Design

• Study Type: Interventional
• Study Design: Not specified