None listed
Conditions
Interventions
Drug : a patient will take ponatinib by mouth, once per day at the starting dose of 45 mg
Sponsors
The Catholic University of Korea, Seoul St. Mary's Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients must have CML in any phase (CP, AP, or BP of any phenotype) or Ph+ ALL 2. Be previously treated with and resistant, or intolerant, to either dasatinib or nilotinib: 2.1 Resistance is defined for CML CP patients (CP at the time of initiation of dasatinib or nilotinib therapy) as follows. Patients must meet at least 1 criterion. a. Three months after the initiation of therapy: No cytogenetic response (>95% Ph+) or failure to achieve CHR. b. Six months after the initiation of therapy: Less than a minor cytogenetic response (>65% Ph+). c. Twelve months after the initiation of therapy: Less than a PCyR (>35% Ph+). d. At any time after the initiation of therapy, the development of new BCR-ABL kinase domain mutations in the absence of CCyR. e. At any time after the initiation of therapy, the development of new clonal evolution in the absence of CCyR. f. At any time after the initiation of therapy, the loss of any cytogenetic response [from complete (0%), partial (1% to 35%), minor (36% to 65%), or minimal (66% to 95%) to a response at least 1 grade worse], confirmed in at least 2 consecutive analyses separated by at least 4 weeks. g. At any time after the initiation of therapy, progression of disease (to AP or BP). 2.2 Resistance is defined for CML AP patients (AP at the time of initiation of dasatinib or nilotinib therapy) as follows. Patients must meet at least 1 criterion. a. Three months after the initiation of therapy: failure to achieve a MaHR. b. At any time after the initiation of therapy, the loss of a MaHR, confirmed in at least 2 consecutive analyses separated by at least 4 weeks. c. At any time after the initiation of therapy, the development of new BCR-ABL kinase domain mutations in the absence of a MaHR. 2.3 Resistance is defined for CML BP patients (BP at the time of initiation of dasatinib or nilotinib therapy) and Ph+ ALL patients as follows. Patients must meet at least 1 criterion. a. One month after the initiation of therapy: failure to achieve a MaHR. b. At any time after the initiation of therapy, the loss of a MaHR, confirmed in at least 2 consecutive analyses separated by at least 1 week. c. At any time after the initiation of therapy, the development of new BCR-ABL kinase domain mutations in the absence of a MaHR. 2.4 Intolerance to dasatinib or nilotinib is defined as: a. Non-hematologic intolerance: Patients with grade 3 or 4 toxicity while on therapy, or with persistent grade 2 toxicity, unresponsive to optimal management, including dose adjustments (unless dose reduction is not considered in the best interest of the patient if response is already suboptimal) in the absence of a CCyR for CP patients or MaHR for AP, BP or Ph+ ALL patients. b. Hematologic intolerance: Patients with grade 3 or 4 toxicity (absolute neutrophil count [ANC] or platelets) while on therapy that is recurrent after dose reduction to the lowest doses recommended by manufacturer (80 mg daily [QD] for dasatinib; 400 mg QD for nilotinib) in the absence of a CCyR for CP patients or MaHR for AP, BP or Ph+ ALL patients. 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 w
Exclusion criteria
Exclusion criteria: 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. 2. 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 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). 16. Are pregnant or lactating. Women of childbearing potential must agree to effective contraception from the time of signing informed consent through the Follow-up Visit, approximately 30 days after last dose of ponatinib. 17. Underwent major surgery (with the exception of minor surgical procedures, such as catheter placement or BM biopsy) within 14 days pri
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| For CML patients in CP at study entry: MCyR, defined as CCyR or PCyR.;For CML patients in AP at study entry: MaHR, defined as CHR or no NEL;For CML patients in BP at study entry or Ph+ ALL patients: MaHR, consisting of CHR or NEL | — |
Secondary
| Measure | Time frame |
|---|---|
| For all patients: time to response, duration of response, progression free survival, and overall survival;For CML patients in CP:a. Hematologic responses: CHR b.Cytogenetic responses: confirmed MCyR c.Molecular responses: MMR;For CML patients in AP or BP or Ph+ ALL patients: a. Cytogenetic responses: CCyR, PCyR, confirmed MCyR b. Molecular responses: MMR | — |
Countries
Korea, Republic of
Contacts
Public ContactSa Hee Park
The Catholic University of Korea, Seoul St. Mary's Hospital
Outcome results
None listed