Phase II Study of the Combination of Blinatumomab and Ponatinib in Patients With Philadelphia Chromosome (Ph)-Positive and/or BCR-ABL Positive Acute Lymphoblastic Leukemia (ALL)
This phase II trial studies how well blinatumomab, methotrexate, cytarabine, and ponatinib work in treating patients with Philadelphia chromosome (Ph)-positive, or BCR-ABL positive, or acute lymphoblastic leukemia that has come back or does not respond to treatment. Immunotherapy with monoclonal antibodies, such as blinatumomab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as methotrexate and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Ponatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving blinatumomab, methotrexate, cytarabine, and ponatinib may work better in treating patients with acute lymphoblastic leukemia.
• Diagnosis of one of the following:
∙ Participants ≥ 18 years of age with previously untreated Ph-positive ALL \[either t(9;22) and/or BCR-ABL positive\] (includes patients initiated on first course of therapy before cytogenetics known) or with lymphoid accelerated or blast phase CML. These participants could have received one or two courses of chemotherapy with or without other TKIs and still eligible. (Participants with lymphoid accelerated or blast phase CML will be evaluated separately) i. If they achieved CR, they are assessable only for event-free and overall survival, or ii. If they failed to achieve CR, they are assessable for CR, event-free, and overall survival
‣ Participants ≥ 18 years of age with relapsed/refractory Ph-positive ALL or with previously treated lymphoid accelerated or blast phase CML (Participants with lymphoid accelerated or blast phase CML will be evaluated separately)
‣ Participants ≥ 18 years of age with ALL MRD positive (either by NGS or PCR or flowcytometry) or with previously treated lymphoid accelerated or blast phase CML (Participants with lymphoid accelerated or blast phase CML will be evaluated separately)
• Performance status ≤ 2 (ECOG Scale)
• Adequate liver function as defined by the following criteria (unless the increased values are judged to be leukemia disease related):
∙ Total serum bilirubin ≤ 2 x upper limit of normal (ULN), unless due to Gilbert's syndrome
‣ Alanine aminotransferase (ALT) ≤ 3 x ULN, OR
‣ Aspartate aminotransferase (AST) ≤ 3 x ULN
• Adequate pancreatic function as defined by the following criteria:
• a) Serum lipase and amylase ≤ 1.5 x ULN
• For females of childbearing potential, a negative urine pregnancy test must be documented
• Female participants who:
‣ Are postmenopausal for at least 1 year before the screening visit, OR
⁃ Are surgically sterile, OR
⁃ If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 4 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse
• Male patients, even if surgically sterilized (i.e., status post-vasectomy), who:
‣ Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or
⁃ Agree to completely abstain from heterosexual intercourse
• Adequate cardiac function as assessed clinically by history and physical examination.
• Signed informed consent