This phase II trial studies the activity and side effects of blinatumomab in combination with tyrosine kinase inhibitor (TKI) therapy and corticosteroids in treating patients with Philadelphia chromosome positive acute lymphoblastic leukemia. Blinatumomab is a bispecific antibody that binds to two different proteins—one on the surface of cancer cells and one on the surface of cells in the immune system. An antibody is a protein made by the immune system to help fight infections and other harmful processes/cells/molecules. Blinatumomab may bind to the cancer cell and a T cell (which plays a key role in the immune system's fighting response) at the same time. Blinatumomab may strengthen the immune system's ability to fight cancer cells by activating the body's own immune cells to destroy the tumor. TKI therapy may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Corticosteroids are naturally occurring hormones that have immune suppressive effect and are used to treat some side effects of cancer and its treatment. Giving blinatumomab in combination with corticosteroid and TKI therapy may work better in treating patients with acute lymphoblastic leukemia compared to corticosteroid and TKI therapy alone.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT04329325.
PRIMARY OBJECTIVE:
I. To determine the proportion of evaluable patients achieving minimal residual disease (MRD) negativity by multiparameter flow cytometry and quantitative polymerase chain reaction (PCR) of BCR-ABL transcripts (complete molecular response [CMR]) at any time during Part 1 (TKI + corticosteroid induction) or Part 2 of the study (up to 3 cycles of blinatumomab in combination with an oral TKI).
SECONDARY OBJECTIVES:
I. To characterize the safety and toxicity profile of blinatumomab in combination with dasatinib, in those proceeding to Part 2 of the study who remain on dasatinib.
II. To estimate the proportion of patients with CMR or molecular MRD positivity with flow MRD negativity.
III. To describe duration of complete molecular response among patients achieving MRD negativity after dasatinib + corticosteroid induction, followed by 1-3 cycles of blinatumomab in combination with an oral TKI.
IV. To estimate the cumulative incidence of relapse following consolidative therapy with blinatumomab in combination with an oral TKI.
V. To assess event-free survival and overall survival following consolidative therapy with blinatumomab in combination with an oral TKI.
VI. To estimate the proportions of patients first achieving CMR during Part 1 (induction) versus (vs.) Part 2 (consolidation).
EXPLORATORY OBJECTIVES:
I. To characterize the safety and toxicity profile of blinatumomab in combination with TKIs other than dasatinib, in patients who receive a TKI other than dasatinib at any point during Part 2 or Part 3 of the study.
II. To characterize patterns of resistance among patients experiencing progression of ALL following consolidative therapy with blinatumomab in combination with an oral TKI.
III. To describe the above outcomes among patients not undergoing allogeneic hematopoietic cell transplantation in first complete remission (CR1) following consolidative therapy with blinatumomab in combination with an oral TKI.
OUTLINE:
PRE-PHASE: Patients receive dexamethasone orally (PO) once daily (QD) or prednisone PO QD on days -6 to 0.
INDUCTION: Patients receive dasatinib orally PO QD on days 1-42 and dexamethasone PO QD on days 1-24 with a taper on days 25-32 in the absence of disease progression or unacceptable toxicity. Patients who are intolerant to dasatinib may receive nilotinib PO twice daily (BID), bosutinib PO QD, imatinib PO QD, or ponatinib PO QD on days 1-42. Patients who do not achieve a complete response (CR) or complete response with incomplete hematologic recovery (CRi) may receive dasatinib PO QD for an additional 21 days. Patients achieving CR or CRi continue to consolidation therapy.
CONSOLIDATION THERAPY: Patients receive blinatumomab via continuous intravenous (IV) infusion on days 1-28. Treatment repeats every 28 days, followed by 2 weeks off, for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive dasatinib PO QD, nilotinib PO BID, bosutinib PO QD, imatinib PO QD, or ponatinib PO QD as in Induction on days 1-28. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients achieving CMR may undergo allogeneic hematopoietic stem cell transplantation (alloHSCT) or continue to maintenance therapy.
MAINTENANCE THERAPY: Patients receive blinatumomab via continuous IV on days 1-28. Treatment repeats every 28 days, followed by 4 weeks off, for up to 4 additional cycles in the absence of disease progression or unacceptable toxicity. Patients also receive dasatinib PO QD, nilotinib PO BID, bosutinib PO QD, imatinib PO QD, or ponatinib PO QD as in Induction on days 1-28. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorMark Blaine Geyer
