CApivasertib, Venetoclax And Low-intensity chemotheRapY for Adults With ALL/LBL
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.
• Previously untreated 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)
‣ Bone marrow or peripheral blood involvement with ≥20% leukemic blasts. Patients with isolated extramedullary disease that is measurable by CT scan are also eligible.
⁃ Previous therapy with dexamethasone or hydroxyurea given for cytoreductive purposes is allowed.
• 40 years old or older
• ECOG performance status 0-2
• Adequate organ function per protocol criteria
• Patients must be at least 2 weeks from major surgery.
• Patients must voluntarily sign and date an informed consent prior to the initiation of any screening or study-specific procedures.
• Females of childbearing potential will use effective contraception during protocol treatment and for at least 8 months after the last dose. Males with female partners of reproductive potential will use effective contraception during protocol treatment and for at least 5 months after the last dose.