University of Chicago
This is a 3-part study to assess the safety of adding capivasertib to a standard of care treatment regimen consisting of venetoclax and low-intensity chemotherapy. This chemotherapy regimen called mini-hyperCVD consists of the chemotherapy drugs, cyclophosphamide, vincristine, dexamethasone; (part A) alternating with high-dose methotrexate and cytarabine (part B) administered approximately every 28 days. In the first part of the study (Cohort 1), the study seeks to determine the recommended dose of capivasertib that can be safely given with venetoclax and chemotherapy. Several doses of capivasertib may be tested in small groups of subjects in this part of the study. The dose tested will be increased or lowered depending on types and frequency of side effects seen until the best, safe dose is found. Once the recommended, safe dose of capivasertib is found, the study will move on to the second part (Cohort 2) and will treat additional participants to learn more about the safety of giving these drugs together. If the combination is determined to be safe overall, the study will move on to the third part (Cohort 3). In this part of the study, participants will be randomized to receive the mini-hyperCVD and venetoclax alone or with capivasertib.
COHORT 1 Inclusion Criteria * Patients with acute leukemia with lymphoid lineage (B-ALL, T-ALL, ETP-ALL, mixed phenotype or bi-phenotypic) or lymphoblastic lymphoma (B- or T-lineage) that is relapsed or refractory * Bone marrow or peripheral blood involvement with ≥5% leukemic blasts. Patients with isolated extramedullary disease that is measurable by CT scan are also eligible. * 18 years or older * ECOG performance status 0-2 * Adequate organ function meeting protocol criteria * Patients must be at least 2 weeks from major surgery or radiation therapy. A wash-out period of 5 half-lives is…
Capivasertib taken by mouth, twice daily. Dosing will occur on a 4 days on, 3 day off schedule.
Venetoclax will be taken by mouth, once daily.
Some participants will receive rituximab by IV infusion, two doses per cycle during the first four cycles. Whether or not this will be given to participants with leukemia cells that express a protein called CD20.
Some participants will receive cycles of blinatumomab by IV continuous infusion after the initial venetoclax plus chemotherapy phase for a 42-day cycle. Each cycle includes 28 days of blinatumomab dosing followed by a 14-day rest period. This will be given to participants that have a certain type of leukemia call CD19+ B-lineage ALL and who experience a complete remission.
Some participants in Cohorts 1 and 2 will receive nelarabine after cycles 2 and 4 at the discretion of their treating physician.
Participants will receive 8 cycles of chemotherapy consisting of the following drugs. They will receive the part A regimen and part B regimen in alternating cycles. Part A: cyclophosphamide, vincristine, dexamethasone Part B: high dose methotrexate and cytarabine.