Management of Transformed Chronic myeloid leukaemia: Ponatinib and Intensive chemotherapy

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 17

Inclusion Criteria

All of the following:
1. Ph positive or BCRABL positive CML in blastic transformation. Defined as one or more of the following being present: Blasts =30% in peripheral blood or bone marrow Extramedullary blast proliferation or large foci or clusters of blasts in the bone marrow biopsy
2. Age: =18
3. Suitable for intensive chemotherapy (FLAGIDA)
4. Adequate renal function defined as serum creatinine =1.5 X upper limit of normal (ULN)
5. Adequate liver function defined as: Total bilirubin < 1.5 X ULN Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5 X ULN (< 5 X ULN if liver involvement with leukaemia)
6. Normal pancreatic status Lipase = 1.5 X ULN and Amylase = 1.5 X ULN
7. Normal QTcF interval on screening ECG evaluation, defined as QTcF of = 450 ms in males or =470 ms in females.
8. Female and male patients who are of childbearing potential must agree to use an effective form of contraception with their sexual partners throughout participation in this study until 30 days after the last dose of ponatinib.
9. Ability to comply with study procedures, in the Investigator's opinion.
10. Valid Informed Consent

Exclusion Criteria

1. Received chemotherapy other than hydroxycarbamide or anagrelide within 4 weeks of registration
2. Received therapy with a new TKI (i.e. changed TKI) following confirmation of blastic transformation up to two weeks of TKI therapy is allowed for those patients whose CML is in blastic phase at original diagnosis.
3. Previous treatment with intensive acute leukaemiastyle chemotherapy (FLAGIDA)
4. Prior allogeneic or autologous Stem Cell Transplant
5. Significant or active cardiovascular disease, specifically including but not restricted to:
Myocardial infarction within 6 months prior to registration
History of clinically significant atrial or ventricular arrhythmia
Unstable angina within 6 months prior to registration
Congestive heart failure within 6 months prior to registration
History of pancreatitis
6. Uncontrolled hypertriglyceridaemia (>450mg/dL)
7. Are pregnant or lactating
8. Underwent major surgery (with the exception of minor surgical procedures, such as catheter placement or Bone Marrow biopsy) within 14 days prior to registration
9. Suffer from any condition or illness that, in the opinion of the investigator, would compromise patient safety or interfere
with the evaluation of the safety of the study treatment

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Efficacy; Timepoint(s): Efficacy: Complete cytogenetic response (CCyR)

Secondary Outcome Measures

Name	Time	Method
1. Incidence of Cytomegalovirus (CMV) reactivation rate and Graft Versus Host Disease (GVHD); Timepoint(s): post-transplant<br>2. Complete Cytogenetic Response (CCyR); Timepoint(s): within 2 cycles of treatment<br>3. Disease free survival (DFS); Timepoint(s): 3 year<br>4. Haematological response; Timepoint(s): within 2 cycles of treatment<br>5. Major Molecular Response (MMR); Timepoint(s): within 2 cycles of treatment<br>6. Overall survival (OS); Timepoint(s): 3 years <br>7. Relapse rate post allogeneic transplant or maintenance therapy; Timepoint(s): 1 and 3 year<br>8. Tolerability<br>9. Identification of the dose of ponatinib that can be safely delivered in combination <br>10. Toxicity profile of ponatinib + chemotherapy (FLAG-IDA); Timepoint(s): within 6 months or up to transplant (whichever time point arrives first). Toxicities will be measure; treatment related mortality; Timepoint(s): 1 and 3 year

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