Ponatinib for Treatment of Patients with CP-CML after treatment with other TKI has failed
- Conditions
- Adult patients (age = 18) with Chronic Myeloid Leukemia (CML) in Chronic Phase (CP) who have proven to be resistant or intolerant to prior first line Tyrosine Kinase Inhibitor TreatmentMedDRA version: 21.0Level: LLTClassification code 10054352Term: Chronic phase chronic myeloid leukemiaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-000618-30-DE
- Lead Sponsor
- GWT-TUD GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 54
1. Male or female patients =18 years old
2. Diagnosis of Ph-positive (by cytogenetics) or BCR-ABL-positive (by PCR) CP-CML
3. Patients should have demonstrated to have:
• Either a failure of a prior 1st line TKI treatment*,** with either imatinib, dasatinib or nilotinib. A failure is defined as per European LeukemiaNet (ELN) recommendations:
o Less than CHR and/or Ph+ > 95% at or beyond 3 months
o No cytogenetic response (Ph+>35%) and/or BCR-ABL1 >10% at or beyond 6 months
o BCR-ABL (on international scale) >1% and/or Ph+ >0% at or beyond 12 months
o Less than MMR at or beyond 18 months
o Loss of response or development of mutations or other clonal chromosomal abnormalities at any time during the first line TKI treatment
• or an intolerance to prior TKI treatment* (TKI related intolerance) defined as grade 3 or 4 toxicity, or persistent grade 2 toxicity despite optimal management including dose adjustment, or in a patient where dose reductions are considered to be not in the patient’s best interest to obtain an adequate response. At time of enrollment intolerant patients should:
• have lost major molecular response -or-
• not have achieved or have lost major molecular response
(*) Patients with intolerance/failure to TKI combination therapy with Asciminib or PEG-IFN could be considered as eligible after consolidation with CPI.)
(**) Patients that received TKI as medical treatment for CML for no longer than 2 weeks duration prior to First Line TKI therapy are categorized as First Line regimen.)
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
5. Adequate hepatic function as defined by the following criteria:
• Total serum bilirubin =1.5 x upper limit of normal (ULN), unless due to Gilbert’s syndrome, in which case it should be = 3.0xULN)
6. Adequate renal function as defined by the following criterion:
• Creatinine clearance of = 50 mL/min
7. Adequate pancreatic function as defined by the following criterion:
• Serum lipase and amylase =1.5×ULN
8. For patients of childbearing potential, a negative pregnancy test must be documented prior to enrollment. Postmenopausal women must be amenorrhoeic for at least 12 months to be considered of non-childbearing potential
9. Female and male patients who are fertile must agree to use effective forms of contraception with their sexual partners from signing off the informed consent form for this study until 3 months after the end of treatment
10. Provision of written informed consent and specifically the consent to the collection and processing of health-related data
11. Willingness and ability to comply with scheduled visits and study procedures
12. Patients should have discontinued therapy with prior TKI (except hydroxyurea), at least 48 hours prior to start of study therapy
13. Fully recovered from the acute effects of prior cancer therapy before initiation of study drug
14. Patients must have had an eye examination confirming no objectives towards study participation by the ophthalmologist within 8 weeks prior to first treatment. . It is recommended to use Ophthalmoscopy to perform the eye examination (additional tests may be used as clinically indicated or as per physician discretion).The eye examinations should test the retinal vasculature
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 44
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this ag
1. Any 1st line anti-CML treatment other than TK (apart from therapy with hydroxyurea)
2. Any 2nd line therapy with a tyrosine kinase inhibitor (>1 EMA approved TKI for CML, or any investigational non EMA-approved TKI)
3. Concurrent participation in any other clinical trial involving another investigational drug*** within 4 weeks prior to enrollment and throughout participation in PONS-Study
(*** relates to participation during treatment phase/ investigational drug application phase)
4. NYHA cardiac class 3-4 heart disease
5. Cardiac Symptoms within the past 12 months prior recruitment: Patients meeting the following criteria are not eligible:
• History of unstable angina, myocardial infarction, TIA, stroke, peripheral arterial occlusive disease or pulmonary embolism
• Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
• Prolonged QTc interval on pre-entry electrocardiogram (> 450 ms in men, > 470 ms in women) on the Fridericia correction formula
• Congestive heart failure (NYHA Class III or IV) within 3 months prior to first dose of ponatinib
6. Patients with active, uncontrolled psychiatric disorders including: psychosis, major depression, and bipolar disorders
7. Patients with uncontrolled hypertension (defined as sustained systolic blood pressure > 140 mmHg or diastolic > 90 mmHg)
8. Pregnant or breast-feeding women are excluded
9. Patients with history of pancreatitis
10. Patients in accelerated or blast phase, or patients who have ever been documented to be in blast phase CML, are excluded. The definitions of excluded CML phases are as follows:
• Blastic phase: presence of 30% blasts or more in the peripheral blood or bone marrow
• Accelerated phase CML: presence of any of the following features:
o Peripheral or marrow blasts 15% or more
o Peripheral or marrow basophils 20% or more
o Thrombocytopenia < 100 x 10^9/L unrelated to therapy
o Documented extramedullary blastic disease outside liver or spleen
• Clonal evolution defined as the presence of additional chromosomal abnormalities other than the Ph chromosome has historically been included as a criterion for accelerated phase. However, patients with clonal evolution as the only criterion of accelerated phase have a significantly better prognosis. Thus, patients with clonal evolution and no other criteria for accelerated phase will be eligible for this study, but analyzed separately
11. Patients showing an intolerance to the active substance or to any of the other ingredients of the test drug
12.Patients who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities
13.Patients who may be dependent on the sponsor, trial site or investigator
14. Patients with active SARS-CoV-2 infection
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