Clinical Trials /

KISS Study: Kinase Inhibition With Sprycel Start up

NCT03193281

Description:

Chronic myeloid leukaemia (CML) is due to a chromosomal abnormality in white blood cells which results in abnormal multiplication. CML in its earlier, slower growing chronic phase (CP) is well controlled by the tyrosine kinase inhibitor (TKI) drug imatinib, which targets the consequences of the chromosomal abnormality, inducing a response and subsequent remission (as measured using molecular techniques on patient blood or bone marrow samples in the lab). Dasatinib, a newer TKI drug, similar in design to imatinib, gives a more rapid molecular response, however the long term side-effects are less known than imatinib. This study will investigate the efficacy and safety of a treatment plan for patients with newly diagnosed CML-CP, where dasatinib will be used to more rapidly induce a molecular response (MR3.0) within 12 months, after which imatinib will be used to maintain the CML in that remission. It is hypothesised that imatinib is safe and effective in maintaining MR3.0 in patients with CML who achieve MR3.0 at 12 months following initial induction therapy with dasatinib.

Related Conditions:
  • Chronic Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: KISS Study: Kinase Inhibition With Sprycel Start up
  • Official Title: KISS Study: A Phase II Study of Dasatinib Followed by Imatinib in Newly Diagnosed, Previously Untreated Patients With Chronic Phase CML

Clinical Trial IDs

  • ORG STUDY ID: CTNZ-2012-08
  • NCT ID: NCT03193281

Conditions

  • Chronic Myeloid Leukemia

Interventions

DrugSynonymsArms
DasatinibSprycelDasatinib
ImatinibImatinib-AFTDasatinib

Purpose

Chronic myeloid leukaemia (CML) is due to a chromosomal abnormality in white blood cells which results in abnormal multiplication. CML in its earlier, slower growing chronic phase (CP) is well controlled by the tyrosine kinase inhibitor (TKI) drug imatinib, which targets the consequences of the chromosomal abnormality, inducing a response and subsequent remission (as measured using molecular techniques on patient blood or bone marrow samples in the lab). Dasatinib, a newer TKI drug, similar in design to imatinib, gives a more rapid molecular response, however the long term side-effects are less known than imatinib. This study will investigate the efficacy and safety of a treatment plan for patients with newly diagnosed CML-CP, where dasatinib will be used to more rapidly induce a molecular response (MR3.0) within 12 months, after which imatinib will be used to maintain the CML in that remission. It is hypothesised that imatinib is safe and effective in maintaining MR3.0 in patients with CML who achieve MR3.0 at 12 months following initial induction therapy with dasatinib.

Detailed Description

      The KISS Study is a Phase II, multicentre, open-label, prospective non-randomised study of
      treatment modification in response to maintenance of MR3.0 at 12 months. Patients must be
      newly diagnosed with chronic phase CML (CML-CP) (<3 months) and previously untreated with the
      exception of hydroxyurea.

      Patients will be recruited from hospital haematology clinics. The majority of patients will
      have been referred to a haematologist due to suspected CML. Written informed consent will be
      ensured before any study-specific procedures are undertaken or study data collected, however
      the majority of assessments carried out for this study are based on standard of care.

      Patients' eligibility will be determined by the usual procedures carried out for CML
      diagnosis. Results from both diagnostic procedures and confirmatory screening procedures will
      constitute baseline data. Once a patient has had their eligibility confirmed and has signed
      informed consent, they will be enrolled into the trial.

      The trial consists of two stages:

      Stage 1: The first 12 months after recruitment (before the possible switch to imatinib).

      Stage 2: Months 13 - 37.

      The following measurements/data will be recorded throughout the trial at protocol specified
      time points:

        -  Haematology and biochemistry.

        -  PB Q-PCR for BCR-ABL1.

        -  Chest x-ray, ECG, ECHO.

        -  Medical assessment including physical exam, ECOG performance, weight, vital signs,
           assessment of extra medullary disease (liver, lymph nodes and spleen), spleen
           measurement below left costal margin, adverse events and concomitant medications.

        -  Haematological and molecular response assessments.

        -  Treatment adherence assessment.

        -  Patient questionnaire (MDASI-CML).

      All patients will commence dasatinib (Sprycel®) 100 mg daily. Molecular monitoring of blood
      BCR-ABL1 transcripts to measure molecular response will occur 3 monthly by Q-PCR as per
      standard of care procedures. Patients who achieve a BCR-ABL1 level of ≤ 0.1% (MR3.0) by 12
      months on treatment will switch treatment to imatinib 400 mg daily if MR3.0 is confirmed at
      13 months (and they give their consent to switch). Those patients who do not achieve MR3.0 at
      12 months or MR3.0 is not confirmed at 13 months, will remain on dasatinib. Patients with
      confirmed MR3.0 who choose not to switch to imatinib will continue on dasatinib. Patients
      that are intolerant of dasatinib in the first 12 months, those that switch to imatinib at 12
      months and then lose MR3.0 or those intolerant of imatinib will be treated off study.
    

Trial Arms

NameTypeDescriptionInterventions
DasatinibOtherAll patients will begin the study on dasatinib treatment (Sprycel® 100mg once daily oral administration). Those who reach MR3.0 at 12 months (end of Study Stage 1) and achieve a confirmed result at 13 months, will switch to imatinib treatment (Imatinib-AFT 400mg once daily oral administration) for the next 24 months (Study Stage 2). Patients who do not achieve a confirmed MR3.0 result at 13 months will not be eligible to switch to imatinib treatment and will remain on dasatinib treatment, as per Study Stage 1. Patients will be assessed on a 3-monthly basis throughout the study. Those who discontinue dasatinib treatment during the study for reasons other than the planned treatment switch to imatinib at 13 months, will also be followed up every 3 months.
  • Dasatinib
  • Imatinib

Eligibility Criteria

        INCLUSION CRITERIA:

          1. Male or female patients ≥ 18 years of age.

          2. ECOG performance status score of 0-2.

          3. Patients must have all of the following:

               1. Be enrolled within 3 months of initial diagnosis of CML-CP (date of initial
                  diagnosis is the date of first cytogenetic analysis).

               2. Cytogenetic or molecular confirmation of Ph+ or variants of (9;22)
                  translocations.

                  patients may have secondary chromosomal abnormalities in addition to the Ph+.

               3. Documented chronic phase CML as defined by:

                    -  < 15% blasts in peripheral blood and bone marrow.

                    -  < 30% blasts plus promyelocytes in peripheral blood and bone marrow.

                    -  < 20% basophils in peripheral blood.

                    -  ≥ 100 x 109/L platelets (unless considered related to hydroxyurea).

                    -  no evidence of extramedullary leukaemic involvement, with the exception of
                       hepatosplenomegaly.

               4. BCR-ABL1 transcript that can be monitored by Q-PCR.

               5. Baseline full blood count (within 14 days of enrolment) remains consistent with
                  chronic phase CML criteria.

          4. Voluntary written informed consent.

        EXCLUSION CRITERIA:

          1. Any prior treatment for CML with other than hydroxyurea.

          2. Patients with the following laboratory values:

               1. serum bilirubin > 2.0 x the institutional upper limit of the normal range (ULN).

               2. ALT > 2.0 x the institutional upper limit of the normal range (ULN).

               3. creatinine > 2.0 x the institutional upper limit of the normal range (ULN).

               4. International normalised ratio (INR) or partial thromboplastin time (PTT) > 1.5 x
                  ULN, with the exception of patients on treatment with oral anticoagulants.

          3. Patients with uncontrolled medical disease such as diabetes mellitus, thyroid
             dysfunction, neuropsychiatric disorders or infection.

          4. Patients with:

               1. Grade 3/4 cardiac problems as defined by the New York Heart Association Criteria.

               2. Uncontrolled hypertension.

               3. Grade 3/4 respiratory dysfunction.

               4. Past or current history of pleural effusions or pulmonary arterial hypertension.

          5. Patients with known positivity for human immunodeficiency virus (HIV); baseline
             testing for HIV is not required.

          6. Patients who have undergone major surgery within 4 weeks of study Day 0, or who have
             not recovered from prior major surgery.

          7. Patients who are:

               1. pregnant.

               2. breast feeding.

               3. of childbearing potential without a negative pregnancy test on/prior to Day 0.

               4. male or female of childbearing potential unwilling to use barrier contraceptive
                  precautions throughout the trial (postmenopausal women must be amenorrhoeic for
                  at least 12 months to be considered of non-childbearing potential).

          8. Patients with another uncontrolled malignancy with the exception of basal cell skin
             carcinoma or cervical carcinoma in situ.

          9. Patients with positivity for hepatitis B antigen and / or hepatitis B core antibody
             (unless receiving prophylactic therapy with lamivudine or more potent agent)

         10. Patients with a history of non-compliance to medical regimens or who are considered
             potentially unreliable.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To estimate the proportion of patients who remain in MR3.0 for the duration of 2 years following a change of therapy from dasatinib to imatinib at 13 months.
Time Frame:2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:To estimate progression free survival (PFS), failure free survival (FFS) and overall survival (OS) for patients that switch to imatinib at 13 months.
Time Frame:3 years
Safety Issue:
Description:
Measure:To estimate the proportion of patients who regain MR3.0 on dasatinib or another TKI therapy after having a confirmed loss of MR3.0 on imatinib, for patients that switch to imatinib at 13 months.
Time Frame:3 years
Safety Issue:
Description:
Measure:To estimate time to MR3.0, MR4.5 and MR5.0 for patients that switch to imatinib at 13 months.
Time Frame:3 years
Safety Issue:
Description:
Measure:To describe adverse event profiles on Stage 1 and Stage 2 of the study and overall for patients that switch to imatinib at 13 months.
Time Frame:3 years
Safety Issue:
Description:
Measure:To describe the quality of life on Stage 1 and Stage 2 of the study and overall for those that switch to imatinib at 13 months.
Time Frame:3 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Auckland, New Zealand

Trial Keywords

  • Dasatinib
  • Imatinib

Last Updated

March 31, 2020