CApivasertib, Venetoclax And Low-intensity chemotheRapY for Adults With ALL/LBL

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 required for patients who participated in other investigational trials. These patients must have recovered from clinically significant toxicities related to these prior treatments. * 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. Exclusion criteria * Ph-positive ALL, Burkitt's leukemia/lymphoma * Patient is pregnant or breastfeeding * Patients with uncontrolled infection. * Known active hepatitis B or C infection, or uncontrolled human immunodeficiency virus (HIV) infection. Patients with HIV infection, whose disease is controlled with anti-retroviral therapy are eligible, but their highly active antiretroviral therapy (HAART) should be modified to minimize drug interactions. Due to the increased risk of hepatitis B reactivation, all patients with active, previously treated or resolved hepatitis B infection will not be eligible for rituximab treatment if their leukemia expresses \>1% CD20. * Major surgery or radiation therapy within 2 weeks prior to the first study dose * Symptomatic central nervous system (CNS) disease or spinal cord compression * Concurrent active malignancy requiring treatment with potential to influence the endpoint of the clinical trial. Patients with non-melanoma skin cancer, carcinoma in situ of the cervix, localized prostate cancer, past history of malignancy that has been definitively treated, and patients treated with hormonal therapies for solid tumors are eligible. Patients with history of multiple myeloma that does not need active treatment are also eligible. * Uncontrolled cardiac disease * Uncontrolled diabetes mellitus, defined as fasting blood glucose \>160 mg/dL or random blood glucose \>250 mg/dL. Patients with type 1 diabetes mellitus or insulin-dependent diabetes are also excluded. A1c measurements are less reliable in leukemia patients due to anemia and/or need for red cell transfusions. Patients with well-controlled, non-insulin-dependent diabetes are eligible, but their blood glucose must be monitored closely during the study period in consultation with Diabetes specialists. * Other severe acute, chronic medical, psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the treating physician, would make the patient inappropriate for entry into this study. * Patients who cannot discontinue strong CYP3A inducers, grapefruit, grapefruit products, Seville oranges, or star fruit within the 3 days prior to starting venetoclax. COHORT 2 Inclusion criteria * Relapsed or refractory 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 ≥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 required for patients who participated in other investigational trials. These patients must have recovered from clinically significant toxicities related to these prior treatments. * 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. Exclusion criteria * Ph-positive ALL, Burkitt's leukemia/lymphoma * Patient is pregnant or breastfeeding * Patients with uncontrolled infection. Patients with infections that have been controlled for ≥7 days will be eligible. * Known active hepatitis B or C infection, or uncontrolled human immunodeficiency virus (HIV) infection. Patients with HIV infection, whose disease is controlled with anti-retroviral therapy are eligible, but their highly active antiretroviral therapy (HAART) should be modified to minimize drug interactions. Due to the increased risk of hepatitis B reactivation, all patients with active, previously treated or resolved hepatitis B infection will not be eligible for rituximab treatment if their leukemia expresses \>1% CD20. * Major surgery or radiation therapy within 2 weeks prior to the first study dose * Symptomatic central nervous system (CNS) disease or spinal cord compression * Concurrent active malignancy requiring treatment with potential to influence the endpoint of the clinical trial. Patients with non-melanoma skin cancer, carcinoma in situ of the cervix, localized prostate cancer, past history of malignancy that has been definitively treated, and patients treated with hormonal therapies for solid tumors are eligible. Patients with history of multiple myeloma that does not need active treatment are also eligible. * Uncontrolled cardiac disease * Uncontrolled diabetes mellitus, defined as fasting blood glucose \>160 mg/dL or random blood glucose \>250 mg/dL. Patients with type 1 diabetes mellitus or insulin-dependent diabetes are also excluded. A1c measurements are less reliable in leukemia patients due to anemia and/or need for red cell transfusions. Patients with well-controlled, non-insulin-dependent diabetes are eligible, but their blood glucose must be monitored closely during the study period in consultation with Diabetes specialists. * Other severe acute, chronic medical, psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the treating physician, would make the patient inappropriate for entry into this study. * Patients who cannot discontinue strong CYP3A inducers, grapefruit, grapefruit products, Seville oranges, or star fruit within the 3 days prior to starting venetoclax. Inclusion criteria * 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. Exclusion criteria * Ph-positive ALL, Burkitt's leukemia/lymphoma * Patient is pregnant or breastfeeding * Patients with uncontrolled infection. Patients with infections that have been controlled for ≥7 days will be eligible. * Known active hepatitis B or C infection, or uncontrolled human immunodeficiency virus (HIV) infection. Patients with HIV infection, whose disease is controlled with anti-retroviral therapy are eligible, but their highly active antiretroviral therapy (HAART) should be modified to minimize drug interactions. Due to the increased risk of hepatitis B reactivation, all patients with active, previously treated or resolved hepatitis B infection will not be eligible for rituximab treatment if their leukemia expresses \>1% CD20. * Major surgery or radiation therapy within 2 weeks prior to the first study dose * Symptomatic central nervous system (CNS) disease or spinal cord compression * Concurrent active malignancy requiring treatment with potential to influence the endpoint of the clinical trial. Patients with non-melanoma skin cancer, carcinoma in situ of the cervix, localized prostate cancer, past history of malignancy that has been definitively treated, and patients treated with hormonal therapies for solid tumors are eligible. Patients with history of multiple myeloma that does not need active treatment are also eligible. * Uncontrolled cardiac disease * Uncontrolled diabetes mellitus, defined as fasting blood glucose \>160 mg/dL or random blood glucose \>250 mg/dL. Patients with type 1 diabetes mellitus or insulin-dependent diabetes are also excluded. A1c measurements are less reliable in leukemia patients due to anemia and/or need for red cell transfusions. Patients with well-controlled, non-insulin-dependent diabetes are eligible, but their blood glucose must be monitored closely during the study period in consultation with Diabetes specialists. * Other severe acute, chronic medical, psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the treating physician, would make the patient inappropriate for entry into this study. * Any prior systemic chemotherapy or radiotherapy for treatment of ALL/LBL is an exclusion with the exception of hydroxyurea, steroids, ATRA and/or intrathecal chemotherapy. No more than 2 weeks of steroids is permitted. * Patients who cannot discontinue strong CYP3A inducers, grapefruit, grapefruit products, Seville oranges, or star fruit within the 3 days prior to starting venetoclax.