Chronic Myeloid LeukemiaPhase 2KISSNCT03193281
KISS Study: Kinase Inhibition With Sprycel Start up
A Phase 2 study testing Dasatinib and Imatinib in people with Chronic Myeloid Leukemia, run by University of Auckland, New Zealand at 9 sites in New Zealand.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Myeloid Leukemia
- What is being tested?
- Dasatinib and Imatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 91 participants
- Where
- 9 sitesNew Zealand
- Study dates
- 17 Jul 2017to 31 Dec 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients ≥ 18 years of age.
- ECOG performance status score of 0-2.
- Patients must have all of the following:
- Be enrolled within 3 months of initial diagnosis of CML-CP (date of initial diagnosis is the date of first cytogenetic analysis).
- Cytogenetic or molecular confirmation of Ph+ or variants of (9;22) translocations.
- patients may have secondary chromosomal abnormalities in addition to the Ph+.
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- 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.
- BCR-ABL1 transcript that can be monitored by Q-PCR.
- Baseline full blood count (within 14 days of enrolment) remains consistent with chronic phase CML criteria.
- Voluntary written informed consent.
Who cannot join
- Any prior treatment for CML with other than hydroxyurea.
- Patients with the following laboratory values:
- serum bilirubin > 2.0 x the institutional upper limit of the normal range (ULN).
- ALT > 2.0 x the institutional upper limit of the normal range (ULN).
- creatinine > 2.0 x the institutional upper limit of the normal range (ULN).
- International normalised ratio (INR) or partial thromboplastin time (PTT) > 1.5 x ULN, with the exception of patients on treatment with oral anticoagulants.
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- Patients with uncontrolled medical disease such as diabetes mellitus, thyroid dysfunction, neuropsychiatric disorders or infection.
- Patients with:
- Grade 3/4 cardiac problems as defined by the New York Heart Association Criteria.
- Uncontrolled hypertension.
- Grade 3/4 respiratory dysfunction.
- Past or current history of pleural effusions or pulmonary arterial hypertension.
- Patients with known positivity for human immunodeficiency virus (HIV); baseline testing for HIV is not required.
- Patients who have undergone major surgery within 4 weeks of study Day 0, or who have not recovered from prior major surgery.
- Patients who are:
- pregnant.
- breast feeding.
- of childbearing potential without a negative pregnancy test on/prior to Day 0.
- 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).
- Patients with another uncontrolled malignancy with the exception of basal cell skin carcinoma or cervical carcinoma in situ.
- Patients with positivity for hepatitis B antigen and / or hepatitis B core antibody (unless receiving prophylactic therapy with lamivudine or more potent agent)
- Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
New Zealand9 sites
Auckland City Hospital
Auckland
Middlemore Hospital
Auckland
Christchurch Hospital
Christchurch
Dunedin Hospital
Dunedin
Waikato Hospital
Hamilton, 3204
Taranaki Base Hospital
New Plymouth, 4310
Palmerston North Hospital
Palmerston North
North Shore Hospital
Takapuna, 0622
Wellington Hospital
Wellington
About this study
Official title: KISS Study: A Phase II Study of Dasatinib Followed by Imatinib in Newly Diagnosed, Previously Untreated Patients With Chronic Phase CML
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.
Read the 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.
- Conditions
- Chronic Myeloid Leukemia
- Being tested
- Dasatinib, Imatinib
- Keywords
- Dasatinib, Imatinib
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DasatinibDrug
Also called Sprycel
In order to test the study hypothesis patients need to stay on dasatinib (Sprycel) treatment for the first 12 months of the study (Stage 1).
Patients who do not reach MR3.0 at 12 months will remain on dasatinib treatment.
ImatinibDrug
Also called Imatinib-AFT
Patients who reach MR3.0 at 12 months (and the result is confirmed at 13 months) will switch to imatinib (Imatinib-AFT) treatment.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Dasatinib; Drug: Imatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 years
Secondary outcomes (5)
To estimate progression free survival (PFS), failure free survival (FFS) and overall survival (OS) for patients that switch to imatinib at 13 months.
Measured: 3 years
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.
Measured: 3 years
To estimate time to MR3.0, MR4.5 and MR5.0 for patients that switch to imatinib at 13 months.
Measured: 3 years
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.
Measured: 3 years
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.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2017
- Study start17 Jul 2017
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- A Phase II, multicentre, open-label, prospective non-randomised study of treatment modification in response to maintenance of MR3.0 at 12 months. Molecular response will be measured 3 monthly. Patients who achieve MR3.0 by 12 months, with a confirmed response at 13 months on treatment, will switch treatment to imatinib. Those patients who do not achieve this confirmed response will remain on dasatinib. For patients who achieve confirmed MR3.0 by 13 months we define two study stages. Stage 1 is the first 12 months after recruitment (i.e. before the possible switch to imatinib) and Stage 2 includes the months 13 - 37.
- Masking
- None (open label)
- Enrolment
- 91 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Auckland, New Zealand
- Sponsor type
- University, hospital or other
- Collaborators
- Leukaemia & Blood Cancer New Zealand
- Responsible party
- Principal investigator, Peter Browett, University of Auckland, New Zealand
- Investigators
- Peter Browett, MBChB, Principal investigator, University of Auckland, New Zealand
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03193281
- Sponsor's protocol ID
- CTNZ-2012-08
- Acronym
- KISS
- Status last verified
- Nov 2023
- First submitted
- 15 Jun 2017
- Last updated
- 29 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- KISS Study: A Phase II Study of Dasatinib Followed by Imatinib in Newly Diagnosed, Previously Untreated Patients With Chronic Phase CML
- ClinicalTrials.gov ID
- NCT03193281
- Acronym / sponsor ID
- KISS / CTNZ-2012-08
- Conditions
- Chronic Myeloid Leukemia
- Keywords
- Dasatinib, Imatinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 91 participants (actual)
- Lead sponsor
- University of Auckland, New ZealandUniversity, hospital or other
- Collaborators
- Leukaemia & Blood Cancer New Zealand
- Study start
- 17 Jul 2017 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 20 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- A Phase II, multicentre, open-label, prospective non-randomised study of treatment modification in response to maintenance of MR3.0 at 12 months. Molecular response will be measured 3 monthly. Patients who achieve MR3.0 by 12 months, with a confirmed response at 13 months on treatment, will switch treatment to imatinib. Those patients who do not achieve this confirmed response will remain on dasatinib. For patients who achieve confirmed MR3.0 by 13 months we define two study stages. Stage 1 is the first 12 months after recruitment (i.e. before the possible switch to imatinib) and Stage 2 includes the months 13 - 37.
| Arm | Type | Receives |
|---|---|---|
| Dasatinib | Other | Drug: Dasatinib, Drug: ImatinibAll 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Male or female patients ≥ 18 years of age.
- ECOG performance status score of 0-2.
- Patients must have all of the following:
- patients may have secondary chromosomal abnormalities in addition to the Ph+.
- Voluntary written informed consent.
Key exclusion criteria (22 listed)
- Any prior treatment for CML with other than hydroxyurea.
- Patients with the following laboratory values:
- Patients with uncontrolled medical disease such as diabetes mellitus, thyroid dysfunction, neuropsychiatric disorders or infection.
- Patients with:
- Patients with known positivity for human immunodeficiency virus (HIV); baseline testing for HIV is not required.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DasatinibAlso: SprycelIn order to test the study hypothesis patients need to stay on dasatinib (Sprycel) treatment for the first 12 months of the study (Stage 1). Patients who do not reach MR3.0 at 12 months will remain on dasatinib treatment. | Drug | Dasatinib |
| ImatinibAlso: Imatinib-AFTPatients who reach MR3.0 at 12 months (and the result is confirmed at 13 months) will switch to imatinib (Imatinib-AFT) treatment. | Drug | Dasatinib |
Primary outcome
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
5 secondary outcomes
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
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
To estimate time to MR3.0, MR4.5 and MR5.0 for patients that switch to imatinib at 13 months.
Time frame: 3 years
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
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Browett, MBChB principal investigator
University of Auckland, New Zealand
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dasatinib and Imatinib in people with Chronic Myeloid Leukemia, run by University of Auckland, New Zealand at 9 sites in New Zealand.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2023.