ot applicable
- Conditions
- Patients with Refractory Chronic Myeloid Leukemia and Ph+ Acute Lymphoblastic LeukemiaMedDRA version: 17.0 Level: LLT Classification code 10024329 Term: Leukemia System Organ Class: 100000004864Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2010-020414-28-BE
- Lead Sponsor
- ARIAD Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 450
1. Patients must have CML in any phase (CP, AP, or BP of any phenotype) or Ph+ ALL (defined in Sections 12.3 and 12.4 of the protocol pages 53 and 54 ).
a. All patients must have screening bone marrow (BM) cytogenetics with conventional banding performed within 42 days prior to initiating treatment.
b. Examination of at least 20 metaphases is required. If less than 20 metaphases are examined, the BM aspirate should be repeated. Patients must either meet criterion 2 or 3:
2. Be previously treated with and resistant, or intolerant, to either dasatinib or nilotinib: For resistance or intolerance criteria please refer to protocol pages 50-51.
OR
3. Develop the T315I mutation after any TKI therapy.
3.1 Patients with T315I mutation after any TKI need not have been treated with dasatinib or nilotinib.
3.2 Patients with T315I in CP must have less than a CCyR (>0% Ph+).
3.3 Patients with T315I in AP, BP, or Ph+ ALL must have less than a MaHR.
3.4 Patients with any history of T315I mutation will be eligible for study participation. However, only those patients who carry a T315I mutation that is detected by direct sequencing in a pre-treatment blood sample using the study’s central laboratory will be analyzed in the T315I subset. Details are provided in Section 12.5.
Patients must meet all of the remaining criteria to be eligible for the study:
4. Patients must be =18 years old.
5. Provide written informed consent.
6. Eastern Cooperative Oncology Group (ECOG) performance status = 2.
7. Minimum life expectancy of 3 months or more.
8. Adequate renal function defined as serum creatinine < 1.5× upper limit of normal (ULN) for institution.
9. Adequate hepatic function defined as:
a. Total bilirubin <1.5 × ULN,
b. Alanine aminotransferase (ALT [SGPT]) and aspartate aminotransferase (AST [SGOT]) < 2.5 × ULN for institution (< 5 x ULN if liver involvement with leukemia),
c. Prothrombin time (PT) < 1.5 × ULN.
10. Normal pancreatic status defined as:
a. Lipase = 1.5 × ULN,
d. Amylase = 1.5 × ULN.
11. Normal QTcF interval on screening ECG evaluation, defined as QTcF of = 450 ms in males or = 470 ms in females.
12. For females of childbearing potential, a negative pregnancy test must be documented prior to enrollment.
13. 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.
14. Ability to comply with study procedures, in the Investigator’s opinion.
Are the trial subjects under 18? no
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 65
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 65
Patients are not eligible for participation in the study if they meet any of the following exclusion criteria:
1. Received TKI therapy within 7 days prior to receiving the first dose of ponatinib, or have not recovered (> grade 1 by NCI CTCAE, v. 4.0) from AEs (except alopecia) due to agents previously administered.
Received other therapies as follows:
a. For CP and AP patients, received hydroxyurea or anagrelide within 24 hours prior to receiving the first dose of ponatinib, interferon, cytarabine, or immunotherapy within 14 days, or any other cytotoxic chemotherapy, radiotherapy, or investigational therapy within 28 days prior to receiving the first dose of ponatinib.
b. For BP patients, received chemotherapy within 14 days prior to the first dose of ponatinib. Otherwise 2a applies.
c. For Ph+ ALL patients, received corticosteroids within 24 hours before the first dose of ponatinib, or vincristine within 7 days prior to the first dose of ponatinib, or received other chemotherapy within 14 days prior to the first dose of ponatinib. Otherwise, 2a applies.
d. All patients are excluded if they have not recovered (> grade 1 by NCI CTCAE, v. 4.0) from AEs (except alopecia) due to agents previously administered.
3. Underwent autologous or allogeneic stem cell transplant < 60 days prior to receiving the first dose of ponatinib; any evidence of on-going graft-versus-host disease (GVHD), or GVHD requiring immunosuppressive therapy.
4. Take medications that are known to be associated with Torsades de Pointes. These medications are listed in Attachment B.
5. Require concurrent treatment with immunosuppressive agents, other than corticosteroids prescribed for a short course of therapy.
6. Have previously been treated with ponatinib.
7. Patient with CML CP are excluded if they are in CCyR.
8. Patients with CML AP, BP, or Ph+ ALL are excluded if they are in MaHR.
9. Have active central nervous system (CNS) disease as evidenced by cytology or pathology. In the absence of clinical CNS disease, lumbar puncture is not required. History itself of CNS involvement is not exclusionary if CNS has been cleared with a documented negative lumbar puncture.
10. Have significant or active cardiovascular disease, specifically including, but not restricted to:
a. Myocardial infarction within 3 months prior to first dose of ponatinib,
b. History of clinically significant atrial arrhythmia or any ventricular arrhythmia,
c. Unstable angina within 3 months prior to first dose of ponatinib,
d. Congestive heart failure within 3 months prior to first dose of ponatinib.
11. Have a significant bleeding disorder unrelated to CML or Ph+ ALL.
12. Have a history of pancreatitis or alcohol abuse.
13. Have uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL).
14. Have malabsorption syndrome or other gastrointestinal illness that could affect absorption of orally administered ponatinib.
15. Have been diagnosed with another primary malignancy within the past 3 years (except for non-melanoma skin cancer or cervical cancer in situ, or controlled prostate cancer, which are allowed within 3 years).
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