KISS Study: Kinase Inhibition With Sprycel Start up

NCT03193281 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: CTNZ-2012-08
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 9

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.

Conditions

Chronic Myeloid Leukemia

Keywords

Dasatinib; Imatinib

Outcome Measures

Primary Outcomes (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.

  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.

  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.

  3 years

• To estimate time to MR3.0, MR4.5 and MR5.0 for patients that switch to imatinib at 13 months.

  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.

  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.

  3 years

Other Outcomes (4)

• 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.

  3 years

• 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.

  3 years

• 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.

  3 years

Study Arms (1)

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.

Drug: Dasatinib; Drug: Imatinib

Interventions

Dasatinib DRUG

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.

Also known as: Sprycel

Dasatinib

Imatinib DRUG

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

Also known as: Imatinib-AFT

Dasatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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+.
• 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.

You may not qualify if:

• 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.
• 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:

Sponsors & Collaborators

• University of Auckland, New Zealand: lead
• Leukaemia & Blood Cancer New Zealand: collaborator

Study Sites (9)

Auckland City Hospital

Auckland, New Zealand

Location

Middlemore Hospital

Auckland, New Zealand

Location

Christchurch Hospital

Christchurch, New Zealand

Location

Dunedin Hospital

Dunedin, New Zealand

Location

Waikato Hospital

Hamilton, 3204, New Zealand

Location

Taranaki Base Hospital

New Plymouth, 4310, New Zealand

Location

Palmerston North Hospital

Palmerston North, New Zealand

Location

North Shore Hospital

Takapuna, 0622, New Zealand

Location

Wellington Hospital

Wellington, New Zealand

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Dasatinib; Imatinib Mesylate

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Benzamides; Amides; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines

Study Officials

• Peter Browett, MBChB

  University of Auckland, New Zealand

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 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.

Study Record Dates

• First Submitted: June 15, 2017
• First Posted: June 20, 2017
• Study Start: July 17, 2017
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: November 29, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (9)