A Study of Ponatinib With Chemotherapy in Children, Teenagers, and Adults With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

The drug being tested in this study is called ponatinib. Ponatinib is being tested to treat pediatric population who have Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), Ph+ mixed phenotype acute leukemia (Ph+ MPAL), or Philadelphia chromosome-like ALL who have relapsed or are resistant or intolerant to a prior tyrosine kinase inhibitor (TKI)-containing therapy, or who have the T315I mutation. The study will enroll approximately 68 participants. Participants will be assigned to a treatment group either in phase 1 or phase 2. Participants unable to swallow the ponatinib tablets or who are receiving less than a 10 mg dose will receive the age-appropriate formulation, capsule with ponatinib minitablets inside: • Ponatinib + Chemotherapy All participants will be asked to take ponatinib once daily. In phase 1 ponatinib will be administered in combination with a chemotherapy backbone to determine the recommended phase 2 dose (RP2D) of ponatinib. In both phase 1 and phase 2, treatment consists of two 35-day blocks of therapy (reinduction block and consolidation block). Each block will include 29 days of treatment of daily ponatinib and a chemotherapy backbone regimen followed by a rest period from chemotherapy for a minimum of 6 days consisting of daily ponatinib only. This is a multi-center trial and will be conducted worldwide. The overall time to participate in this study is 6.5 years. Participants will make multiple visits to the clinic, and may be contacted by telephone in at least 36 months of follow-up after treatment.