Front-line Treatment of Philadelphia Positive (Ph+)/BCR-ABL Positive Acute Lymphoblastic Leukemia (ALL) With AP24534 (Ponatinib), a New Potent Tyrosine Kinase Inhibitor (TKI). A Phase II Exploratory Multicentric Study in Patients More Than 60 Years Old or Unfit for a Program of Intensive Chemotherapy and Stem Cell Transplantation.
This is a multi-center, phase 2, single arm unblinded trial of oral Ponatinib in patients
with Ph+ Acute Lymphoblastic Leukemia. Patients will receive daily oral administration of
Ponatinib at a dose of 45 mg/day for 6 weeks (defined as one course) for 8 courses, same
dose and schedule, for a total of 48 weeks. Each patient will be followed for the subsequent
24 months, every 3 month, providing survival information and monitoring serious adverse
Each patient should be treated for a minimum of 6 weeks. Then a patient can be discontinued
in the following situation:
- at the end of first course (6 weeks), in case of lack of CHR;
- at the end of third course (18 weeks), in case of lack of CCgR;
- any time in case of loss of CHR or CCgR. If they remain on therapy after 48 weeks, they
will be able to continue treatment during the extension phase of the study, if it is of
interest of the patient, or they will be allowed to receive any treatment that is in
their interest. For all the patients remaining on trial, response, outcome and toxicity
will be followed for the subsequent 24 months.The 6-weeks periodicity must be rigidly
respected, irrespective of the temporary discontinuation of study drug (eg, if a
patient will take Ponatinib only for 4 weeks and will remain off-treatment for the
subsequent two weeks because of AE, when the 7th week begins this patient will restart
Ponatinib as a second course, as per protocol). Prednisone (P) will be administered to
all patients for 7-14 days, before Ponatinib, so as to make it possible to wait for the
results of cytogenetic and molecular tests, and to evaluate the response to P alone,
hence for another 21 days. Intrathecal therapy (IT) with MTX/AraC/DEX is mandatory,
every 28 days, in patients without clinical-cytologic evidence of meningeal
involvement. In patients with CNS disease, IT is performed twice weekly until a
complete clearance of cerebrospinal fluid blast cells is achieved, hence once weekly
for 4 weeks, hence once monthly.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Proportion of patients who are in Complete Hematological Response (CHR).
The primary endpoint is the proportion of patients who are in CHR at 6 months, calculated on the total number of patients who have been enroled and have received at least one dose of the first drug (prednisone).
At 6 months from study entry.
Michele Baccarani, Pr.
Dpt of Hematology and Oncology "Seràgnoli", "Sant'Orsola-Malpighi" University Hospital of Bologna
Italy: The Italian Medicines Agency