Trial to Test Safety of Adding Capivasertib to a Standard Leukemia Treatment Regimen
NCT ID: NCT07294677
Last Updated: 2025-12-19
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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NOT_YET_RECRUITING
PHASE1/PHASE2
104 participants
INTERVENTIONAL
2026-03-17
2032-03-31
Brief Summary
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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.
Detailed Description
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Conditions
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Keywords
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Cohort 1 - Dose Escalation (Dose Level 1)
In this arm, a dose of 320 mg dose of capivasertib will be tested in combination with venetoclax and mini-hyperCVD chemotherapy regimen.
Capivasertib
Capivasertib taken by mouth, twice daily. Dosing will occur on a 4 days on, 3 day off schedule.
Venetoclax
Venetoclax will be taken by mouth, once daily.
Rituximab
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.
Blinatumomab
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.
Nelarabine
Some participants in Cohorts 1 and 2 will receive nelarabine after cycles 2 and 4 at the discretion of their treating physician.
mini-hyperCVD
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.
Cohort 1 - Dose Escalation (Dose Level 2)
In this arm, a dose of 400 mg dose of capivasertib will be tested in combination with venetoclax and mini-hyperCVD chemotherapy regimen.
Capivasertib
Capivasertib taken by mouth, twice daily. Dosing will occur on a 4 days on, 3 day off schedule.
Venetoclax
Venetoclax will be taken by mouth, once daily.
Rituximab
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.
Blinatumomab
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.
Nelarabine
Some participants in Cohorts 1 and 2 will receive nelarabine after cycles 2 and 4 at the discretion of their treating physician.
mini-hyperCVD
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.
Cohort 1 - Dose Escalation (Dose Level -1)
In this arm, a dose of 200 mg dose of capivasertib will be tested in combination with venetoclax and mini-hyperCVD chemotherapy regimen.
Capivasertib
Capivasertib taken by mouth, twice daily. Dosing will occur on a 4 days on, 3 day off schedule.
Venetoclax
Venetoclax will be taken by mouth, once daily.
Rituximab
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.
Blinatumomab
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.
Nelarabine
Some participants in Cohorts 1 and 2 will receive nelarabine after cycles 2 and 4 at the discretion of their treating physician.
mini-hyperCVD
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.
Cohort 2 (Expansion)
In this arm, the best, safe dose of capivasertib found after completion of enrollment to dose escalation (cohort 1) arms, will be tested in combination with venetoclax and mini-hyperCVD chemotherapy regimen.
Capivasertib
Capivasertib taken by mouth, twice daily. Dosing will occur on a 4 days on, 3 day off schedule.
Venetoclax
Venetoclax will be taken by mouth, once daily.
Rituximab
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.
Blinatumomab
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.
Nelarabine
Some participants in Cohorts 1 and 2 will receive nelarabine after cycles 2 and 4 at the discretion of their treating physician.
mini-hyperCVD
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.
Cohort 3 -- Arm 1 -- mini-hyperCVD + venetoclax (Randomized)
Participants randomized to this arm will receive mini-hyperCVD + venetoclax.
Venetoclax
Venetoclax will be taken by mouth, once daily.
Rituximab
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.
Blinatumomab
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.
Nelarabine
Some participants in Cohorts 1 and 2 will receive nelarabine after cycles 2 and 4 at the discretion of their treating physician.
mini-hyperCVD
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.
Cohort 3 -- Arm 2 -- mini-hyperCVD + venetoclax + capivasertib (Randomized)
Participants randomized to this arm will receive mini-hyperCVD + venetoclax and capivasertib.
Capivasertib
Capivasertib taken by mouth, twice daily. Dosing will occur on a 4 days on, 3 day off schedule.
Venetoclax
Venetoclax will be taken by mouth, once daily.
Rituximab
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.
Blinatumomab
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.
Nelarabine
Some participants in Cohorts 1 and 2 will receive nelarabine after cycles 2 and 4 at the discretion of their treating physician.
mini-hyperCVD
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.
Interventions
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Capivasertib
Capivasertib taken by mouth, twice daily. Dosing will occur on a 4 days on, 3 day off schedule.
Venetoclax
Venetoclax will be taken by mouth, once daily.
Rituximab
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.
Blinatumomab
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.
Nelarabine
Some participants in Cohorts 1 and 2 will receive nelarabine after cycles 2 and 4 at the discretion of their treating physician.
mini-hyperCVD
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.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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.
* 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.
* 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
* 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.
* 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.
* 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.
18 Years
ALL
No
Sponsors
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University of Chicago
OTHER
Responsible Party
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Principal Investigators
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Caner Saygin
Role: STUDY_CHAIR
University of Chicago
Locations
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University of Chicago Medicine Comprehensive Cancer Center
Chicago, Illinois, United States
Countries
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Central Contacts
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Facility Contacts
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Clinical Trials Intake
Role: primary
Other Identifiers
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IRB25-1773
Identifier Type: -
Identifier Source: org_study_id