KISS Study: Kinase Inhibition With Sprycel Start up

• Status: Recruiting
• Trial end date: 2025-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Auckland, New Zealand
• Collaborator: Leukaemia & Blood Cancer New Zealand
• Treatments: Dasatinib; Imatinib Mesylate

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.