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KISS Study: Kinase Inhibition With Sprycel Start up (KISS)

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ClinicalTrials.gov Identifier: NCT03193281
Recruitment Status : Recruiting
First Posted : June 20, 2017
Last Update Posted : March 13, 2019
Sponsor:
Collaborator:
Leukaemia & Blood Cancer New Zealand
Information provided by (Responsible Party):
Peter Browett, University of Auckland, New Zealand

Brief 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 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.


Condition or disease Intervention/treatment Phase
Chronic Myeloid Leukemia Drug: Dasatinib Drug: Imatinib Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Intervention Model: Single Group Assignment
Intervention 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)
Primary Purpose: Treatment
Official Title: KISS Study: A Phase II Study of Dasatinib Followed by Imatinib in Newly Diagnosed, Previously Untreated Patients With Chronic Phase CML
Actual Study Start Date : July 17, 2017
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : December 31, 2023


Arm Intervention/treatment
Dasatinib

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.

Drug: Dasatinib

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.

Other Name: Sprycel

Drug: Imatinib
Patients who reach MR3.0 at 12 months (and the result is confirmed at 13 months) will switch to imatinib (Imatinib-AFT) treatment.
Other Name: Imatinib-AFT




Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. To estimate time to MR3.0, MR4.5 and MR5.0 for patients that switch to imatinib at 13 months. [ Time Frame: 3 years ]
  4. 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 ]
  5. 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 ]

Other Outcome Measures:
  1. To estimate PFS, FFS and OS for the following groups: 1) the entire cohort 2) patients not eligible to switch to imatinib at 13 months 3) patients that are eligible but do not switch. [ Time Frame: 3 years ]
  2. To estimate time to MR3.0, MR4.5 and MR5.0 for the following groups: 1) the entire cohort 2) patients not eligible to switch to imatinib at 13 months 3) patients that are eligible but do not switch. [ Time Frame: 3 years ]
  3. To describe adverse event profiles on each stage of study therapy for the following groups: 1) the entire cohort 2) patients not eligible to switch to imatinib at 13 months 3) patients that are eligible but do not switch. [ Time Frame: 3 years ]
  4. To describe the quality of life on each stage of study therapy for the following groups: 1) the entire cohort 2) patients not eligible to switch to imatinib at 13 months 3) patients that are eligible but do not switch. [ Time Frame: 3 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 7 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03193281


Contacts
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Contact: Kate Gorton, MPH +6499234927 kate.gorton@auckland.ac.nz
Contact: Sarah Benge, PhD +6499233585 s.benge@auckland.ac.nz

Locations
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New Zealand
Auckland City Hospital Recruiting
Auckland, New Zealand
Contact: Kate Gorton         
Principal Investigator: Peter Browett         
Middlemore Hospital Recruiting
Auckland, New Zealand
Contact: Kate Gorton         
Principal Investigator: Gordon Royle         
Christchurch Hospital Recruiting
Christchurch, New Zealand
Contact: Kate Gorton         
Principal Investigator: Emma-Jane McDonald         
Dunedin Hospital Recruiting
Dunedin, New Zealand
Contact: Kate Gorton         
Principal Investigator: Lucy Pemberton         
Waikato Hospital Recruiting
Hamilton, New Zealand, 3204
Contact: Kate Gorton         
Principal Investigator: Humphrey Pullon         
Taranaki Base Hospital Recruiting
New Plymouth, New Zealand, 4310
Contact: Kate Gorton         
Principal Investigator: Bart Baker         
Palmerston North Hospital Recruiting
Palmerston North, New Zealand
Contact: Kate Gorton         
Principal Investigator: Bart Baker         
North Shore Hospital Recruiting
Takapuna, New Zealand, 0622
Contact: Kate Gorton         
Principal Investigator: Henry Chan         
Wellington Hospital Recruiting
Wellington, New Zealand
Contact: Kate Gorton         
Principal Investigator: Michelle Dickson         
Sponsors and Collaborators
University of Auckland, New Zealand
Leukaemia & Blood Cancer New Zealand
Investigators
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Principal Investigator: Peter Browett, MBChB University of Auckland, New Zealand

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Responsible Party: Peter Browett, Professor, University of Auckland, New Zealand
ClinicalTrials.gov Identifier: NCT03193281     History of Changes
Other Study ID Numbers: CTNZ-2012-08
First Posted: June 20, 2017    Key Record Dates
Last Update Posted: March 13, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Peter Browett, University of Auckland, New Zealand:
Dasatinib
Imatinib

Additional relevant MeSH terms:
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Leukemia
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Imatinib Mesylate
Dasatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action