Chronic myelogenous leukemia MedDRA version: 21.0 Level: LLT Classification code 10009012 Term: Chronic myelogenous leukemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: ICLUSIG
Product Name: PONATINIB
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: PONATINIB
CAS Number: 943319-70
Sponsors
Fundación CRIS contra el Cáncer
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients = 18 years of age. 2. ECOG Performance Status of 0, 1, or 2. 3. Patient with diagnosis of BCR-ABL positive and Ph+ CML-Chronic Phase. 4. Patient has achieved MR4 for one year with TKI treatment confirmed by RT-qPCR lab assessment at screening after a previous TKI treatment´s discontinuation. 5. Patients who are able to take oral therapy 6. Adequate end organ function as defined by: a. Direct bilirubin = 1.5 x ULN b. SGOT(AST) and SGPT(ALT) = 2.5 x ULN, c. Serum lipase and amylase = 1.5 x ULN, d. Alkaline phosphatase = 2.5 x ULN, e. Serum creatinine = 1.5 x ULN. 7. Patients must have the following electrolyte values = LLN limits or corrected to within normal limits with supplements prior to the first dose of study medication: a. Potassium, b. Magnesium, c. Total calcium (corrected for serum albumin) 8. Patients must have normal marrow function as defined below: a. Absolute Neutrophil Count (ANC) = 1.5 x 109/L, b. Platelets = 100 x 109/L. c. Hemoglobin > 9 g/dL. 9. Patients with preexisting, well-controlled diabetes can be included. 10. Have normal QTcF interval on screening ECG evaluation, defined as QTcF of = 450 ms in males or = 470 ms in females. 11. Have a negative pregnancy test documented prior to enrollment (for females of childbearing potential). diately. 12. Be willing and able to comply with scheduled visits and study procedures. 13. Patients with the ability to comprehend and sign the informed consent 14. Written informed consent obtained prior to any screening procedures. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1. Prior accelerate phase, blast crisis or autologous or allogenic transplant 2. Patients with known atypical transcript. An atypical transcript is defined by the presence of any transcript in the absence of the major transcripts b3a2 (e14a2) and b2a2 (e13a2) or p210 protein. 3. CML treatment resistant mutation(s) (T315I, E255K/V, Y253H, F359C/V) detected if a testing was done in the past (there is no requirement to perform mutation testing at study entry if it was not done in the past). 4. Are taking medications with a known risk of torsades de pointes (Annex 5). 5. Patient ever attempted to permanently discontinue TKI treatment. 6. Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g., uncontrolled diabetes (defined as HbA1c > 9%), uncontrolled infection). 7. Have clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to: a. Any history of MI, unstable angina, cerebrovascular accident, or TIA. b. Any history of peripheral vascular infarction, including visceral infarction. c. Any revascularization procedure, including the placement of a stent. d. Congestive heart failure (NYHA class III or IV) within 6 months prior to enrollment, or LVEF less than lower limit of normal, per local institutional standards, within 6 months prior to enrollment. e. History of clinically significant (as determined by the treating physician) atrial arrhythmia or any history of ventricular arrhythmia. f. Venous thromboembolism, including deep venous thrombosis or pulmonary embolism, within 6 months prior to enrollment. 8. Have uncontrolled hypertension (diastolic blood pressure > 90 mmHg; systolic > 150 mmHg). Patients with hypertension should be under treatment on study entry to effect blood pressure control. 9. Have a history of alcohol abuse. 10. History of acute pancreatitis within 1 year prior to study entry or past medical history of chronic pancreatitis. 11. Have malabsorption syndrome or other gastrointestinal illness that could affect oral absorption of study drug. 12. Known presence of a significant congenital or acquired bleeding disorder unrelated to cancer. 13. Have a history of another malignancy, other than cervical cancer in situ or no metastatic basal cell or squamous cell carcinoma of the skin; the exception is if patients have been disease-free for at least 5 years, and are deemed by the investigator to be at low risk for recurrence of that malignancy. 14. Have undergone major surgery (with the exception of minor surgical procedures, such as catheter placement) within 14 days prior to first dose of ponatinib. 15. Treatment with other investigational agents (defined as not used in accordance with the approved indication) within 4 weeks of Day 1. 16. Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to study entry. See Annex 6 for a list of these medications. This list may not be comprehens
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the proportion of patients still in MMR; Secondary Objective: - Evaluate the toxicity and safety profile of 15 mg/24h dose treatment of ponatinib combined with ASA. - Evaluate thromboembolic, hemorrhagic, hemolytic and gastrointestinal events for study period - Evaluate the proportion of patients still in MR4 - Evaluate the proportion of patients still in MMR - Evaluate the effects of physical activity on treatment response. - Progression-free survival (PFS). - Treatment-free survival (TFS). ;Primary end point(s): Proportion of patients with a maintained MMR within 52 weeks following ponatinib TFR.;Timepoint(s) of evaluation of this end point: Maintained MMR in the first 52 weeks after starting ponatinib TFR | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Incidence of treatment-emergent adverse events (new or worsening from baseline). - Incidence of thromboembolic and hemorrhagic events, hematologic events and gastrointestinal events. - Proportion of patients still in MR4 within 52 weeks following ponatinib TFR. - Proportion of patients who still have a MMR within 24 weeks following ponatinib TFR. - Relate clinical response obtained after stop Ponatinib treatment with subject´s physical activity during 52 weeks - Progression free survival (PFS) - Treatment-free survival (TFS) ; Timepoint(s) of evaluation of this end point: - From Baseline until the end of the study in an ongoing basis. - From Baseline until the end of the study in an ongoing basis. - Number of patients with a maintained MR4 and have not restarted TKI therapy in the first 52 weeks after starting ponatinib TFR phase. - Number of patients who still have a MMR and have not restarted TKI therapy in the first 24 weeks after starting ponatinib TFR phase. - During 52 weeks - From the start ponatinib treatment to the occurrence of progression to AP/BC, loss of MMR or death from any cause. - Time from ponatinib cessation to the occurrence of loss of MMR, restart of TKI treatment, progression of AP/BC, or death from any cause. | — |
Countries
Spain
Contacts
Public ContactClinical Operations Department
APICES SOLUCIONES S.L.
Outcome results
None listed