Management of Transformed Chronic myeloid leukaemia: Ponatinib and Intensive chemotherapy: a dose-finding study

Phase 1

Conditions: Chronic Myeloid Leukaemia (CML) in Blast Phase
MedDRA version: 20.1Level: PTClassification code 10009013Term: Chronic myeloid leukaemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2012-005629-65-GB

Lead Sponsor: niversity of Birmingham

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 15

Inclusion Criteria

All of the following:
•Ph-positive or BCR-ABL positive CML in blastic transformation. Defined as one or more of the following being present:
oBlasts =30% in peripheral blood or bone marrow
oExtramedullary blast proliferation or large foci or clusters of blasts in the bone marrow biopsy
•Age: =16
•Suitable for intensive chemotherapy (FLAG-IDA)
•Adequate renal function defined as serum creatinine =1.5 X upper limit of normal (ULN)
•Adequate liver function defined as:
oTotal bilirubin < 1.5 X ULN, unless due to Gilbert’s syndrome
oAlanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5 X ULN (< 5 X ULN if liver involvement with leukaemia. Patients with disordered liver function >5 X ULN due to leukaemia may enter with a dose reduction of FLAG-IDA as per local guidelines and will be considered on a per patient basis following discussion with the Chief Investigator and Trial Office.)
•Normal pancreatic status defined as:
oSerum Amylase = 1.5 X ULN
•Normal QTcF interval on screening ECG evaluation, defined as QTcF of = 450 ms in males or =470 ms in females.
•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 4 months after the last dose of ponatinib.
•Ability to comply with study procedures, in the Investigator’s opinion.
•Valid Informed Consent

Are the trial subjects under 18? yes
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 3

Exclusion Criteria

•Any of the following will exclude:
•Received chemotherapy other than hydroxycarbamide, anagrelide, low dose arabinosylcytarabine (LDAC), steroids, or interferon within 4 weeks of registration
•Changed TKI therapy more than once since confirmation of blast phase CML or had prior treatment with ponatinib at any time.
•Previous treatment with intensive acute leukaemia-style chemotherapy (FLAG-IDA). (Unless treatment was during an initial blast phase which returned to chronic phase for a prolonged period of time and the patient is now in a second blast phase.)
•Prior allogeneic or autologous Stem Cell Transplant
•Significant or active cardiovascular disease, specifically including but not restricted to:
oMyocardial infarction, stroke or revascularization within 12 months prior to registration
oHistory of clinically significant atrial arrhythmia
oAny history of or ventricular arryhthmia
oUnstable angina or transient ischemic attack within 6 months prior to registration
oCongestive heart failure within 6 months prior to registration
oLeft ventricular ejection fraction (LVEF) less than lower limit of normal within 6 months prior to registration
oAny history of unprovoked venous thromboembolism including deep venous thrombosis or pulmonary embolism
oUncontrolled hypertension (sustained diastolic blood pressure >90 mm Hg; systolic >140 mm Hg).
•History of acute pancreatitis within 1 year prior to registration
•History of chronic pancreatitis.
•Uncontrolled hypertriglyceridaemia (>450 mg/dL)
•Are pregnant or lactating
•Are known galactose intolerant
•Underwent major surgery (with the exception of minor surgical procedures, such as catheter placement or Bone Marrow biopsy) within 14 days prior to registration
•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 clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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