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.
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
Interventions
Drug | Synonyms | Arms |
---|
Dasatinib | Sprycel | Dasatinib |
Imatinib | Imatinib-AFT | Dasatinib |
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
Name | Type | Description | Interventions |
---|
Dasatinib | Other | All 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. | |
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
Last Updated
March 12, 2021