Clinical Trials /

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

NCT01804985

Description:

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).

Related Conditions:
  • Chronic Myeloid Leukemia
Recruiting Status:

Unknown status

Phase:

Phase 2

Trial Eligibility

Document

De- Escalation and Stopping Treatment of <span class="go-doc-concept go-doc-intervention">Imatinib</span>, <span class="go-doc-concept go-doc-intervention">Nilotinib</span> or <span class="go-doc-concept go-doc-intervention">sprYcel</span> in Chronic Myeloid Leukaemia

Title

  • Brief Title: De- Escalation and Stopping Treatment of Imatinib, Nilotinib or sprYcel in Chronic Myeloid Leukaemia
  • Official Title: A Trial of De-escalation and Stopping Treatment in Chronic Myeloid Leukaemia Patients With Excellent Responses to Tyrosine Kinase Inhibitor Therapy
  • Clinical Trial IDs

    NCT ID: NCT01804985

    ORG ID: 4203

    Trial Conditions

    Chronic Myeloid Leukaemia

    Trial Interventions

    Drug Synonyms Arms
    Imatinib Glivec or Gleevec De-escalated Treatment
    nilotinib Tasigna De-escalated Treatment
    dasatinib Sprycel De-escalated Treatment

    Trial Purpose

    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).

    Detailed Description

    The next definitive UK phase III trial in chronic myeloid leukaemia (CML) will be SPIRIT3,
    which will open in Summer 2014. This will incorporate a de-escalation and stopping strategy
    for patients who achieve excellent responses after at least 3 years of treatment with a
    tyrosine kinase inhibitor (TKI).

    DESTINY is to act as a pilot for this strategy in SPIRIT3, by defining the proportion of
    patients that relapse during 12 months of TKI de-escalation followed by 24 months of
    cessation. DESTINY also includes scientific bolt-on studies, quality of life assessments and
    health economic evaluation.

    Trial Arms

    Name Type Description Interventions
    De-escalated Treatment Experimental Imatinib, nilotinib or dasatinib; de-escalated to half the standard dose for 12 months Imatinib, nilotinib, dasatinib

    Eligibility Criteria

    Inclusion Criteria:

    - 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, 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, 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.

    Exclusion Criteria:

    - Age under 18

    - Life expectancy predicted to be less than 37 months because of intercurrent illness
    (e.g. heart, renal, respiratory or active malignant disease) that might preclude
    completion of the study

    - 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.

    - Treatment with higher than standard TKI doses ('standard' is defined as imatinib
    400mg daily, nilotinib 400mg twice daily or dasatinib 100mg daily)

    - Patients who switched previous licensed TKI treatment (imatinib, nilotinib or
    dasatinib) twice or more because of intolerance.

    - Patients who switched previous licensed TKI treatment (imatinib, nilotinib or
    dasatinib) because of resistance.

    - 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.

    - 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.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    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.

    Secondary Outcome Measures

    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

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

    Quality of Life

    Health Economic Assessment

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

    Trial Keywords