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| Name | Class |
|---|---|
| AbbVie | INDUSTRY |
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This research study is studying a medication called Venetoclax and a chemotherapy regimen as a possible treatment for Acute Lymphoblastic Leukemia.
The drugs involved in this study are:
This research study is a Phase I clinical trial, which tests the safety of an investigational drug and drug combination and also tries to define the appropriate dose of the investigational drug and drug combination to use for further studies. "Investigational" means that the drug and drug combination is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved Venetoclax for this specific disease, but it has been approved for other uses.
Venetoclax is an inhibitor of Bcl-2. Bcl-2 is critical for keeping cancer cells alive.
By inhibiting Bcl-2, venetoclax promotes cancer cell death. This drug is currently being used in other clinical trials for people with certain types of leukemia, lymphoma, and multiple myeloma. There is some evidence from those and other laboratory trials that venetoclax may kill cancer cells and cause tumors to shrink.
In this research study, the investigators are investigating how safe the combination of Venetoclax and standard chemotherapy is and how it affects this disease.. The participant will be given Venetoclax alone first and the standard chemotherapies will be given in combination. This study aims to provide information to help determine the dose of Venetoclax , in combination with standard chemotherapy, affects this disease the best and which dose is the safest.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Venetoclax + Chemotherapy | Experimental |
|
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Venetoclax | Drug | Venetoclax is an inhibitor of Bcl-2. Bcl-2 is critical for keeping cancer cells alive. By inhibiting Bcl-2, venetoclax promotes cancer cell death. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose | To determine the maximum tolerated dose (MTD) of venetoclax in combination with chemotherapy in patients with newly diagnosed Acute Lymphoblastic Leukemia (ALL) | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| To Evaluate The Safety of the Combination | To evaluate the safety of this combination in a dose expansion cohort. The proportion of patients having a grade 3 or higher adverse event will be estimated with a 95% confidence interval in the expansion cohort. | 2 years |
| Complete Response |
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Inclusion Criteria:
OR
Patients with relapsed or refractory acute lymphoblastic leukemia (B-cell or T-cell) defined as receiving one or more cytotoxic containing regimens
Bone marrow involvement with ≥5% lymphoblasts
Age ≥ 18 Years
Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Refer to Appendix D)
Adequate organ function
Women of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (β-hCG) pregnancy test result within 14 days prior to the first dose of study drugs and must agree to use an effective contraception method during the study and for 30 days following the last dose of study drug. Women of non- childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy. Men who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 30 days following the last dose of study drug
Patients or their legally authorized representative must provide written informed consent
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Marlise Luskin, MD, MSCE | Dana-Farber Cancer Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Chicago | Chicago | Illinois | 60637 | United States | ||
| Massachusetts General Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39546748 | Derived | Luskin MR, Shimony S, Keating J, Winer ES, Garcia JS, Stone RM, Jabbour E, Flamand Y, Stevenson K, Ryan J, Zeng Z, Letai A, Konopleva M, Jain N, DeAngelo DJ. Venetoclax plus low-intensity chemotherapy for adults with acute lymphoblastic leukemia. Blood Adv. 2025 Feb 11;9(3):617-626. doi: 10.1182/bloodadvances.2024014405. |
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|
| Standard Chemotherapy | Drug | Standard treatment of chemotherapy is administered |
|
To determine the efficacy: complete response (CR) with incomplete marrow recovery (CRi) of venetoclax in combination with chemotherapy in patients with newly diagnosed ALL |
| 2 years |
| Progression Free Survival | To determine the duration of response: progressive-free survival (PFS) and overall survival (OS) of venetoclax in combination with chemotherapy in patients with newly diagnosed ALL | 2 years |
| Overall Survival | To determine the duration of response: progressive-free survival (PFS) and overall survival (OS) of venetoclax in combination with chemotherapy in patients with newly diagnosed ALL | 2 years |
| Minimal Residual Disease | To determine the rate of minimal residual disease (MRD) negativity in patients achieving CR/CRi and its correlation with disease-free survival (DFS) and OS | 2 years |
| Disease Free Survival | To determine the rate of minimal residual disease (MRD) negativity in patients achieving CR/CRi and its correlation with disease-free survival (DFS) and OS | 2 years |
| Change in expression of BCL-2 family proteins: BCL-2 | To measure expression and function of Bcl-2 family proteins and its modulation by venetoclax in ALL blasts. The change in expression of BCL-2 family proteins from baseline to the time of each response assessment will be measured including BCL-2 and summary statistics including the median and interquartile range of the change will be reported for all patients in the expansion cohort and also summarized for those achieving a CR/CRi and those patients who do not achieve a CR/CRi. This is based on section 9.1: We plan to collect bone marrow and peripheral blood samples at baseline, at the time of clinical response assessment and at the time of progression for correlative studies. These will be done in the laboratory of Dr. Marina Konopleva at MDACC and Dr. Tony Letai at DFCI. | 2 years |
| Change in expression of BCL-2 family proteins: BCL-XL | To measure expression and function of Bcl-2 family proteins and its modulation by venetoclax in ALL blasts. The change in expression of BCL-2 family proteins from baseline to the time of each response assessment will be measured including BCL-XL and summary statistics including the median and interquartile range of the change will be reported for all patients in the expansion cohort and also summarized for those achieving a CR/CRi and those patients who do not achieve a CR/CRi. This is based on section 9.1: We plan to collect bone marrow and peripheral blood samples at baseline, at the time of clinical response assessment and at the time of progression for correlative studies. These will be done in the laboratory of Dr. Marina Konopleva at MDACC and Dr. Tony Letai at DFCI. | 2 years |
| Change in expression of BCL-2 family proteins: MCL-1 (anti-apoptotic) | To measure expression and function of Bcl-2 family proteins and its modulation by venetoclax in ALL blasts. The change in expression of BCL-2 family proteins from baseline to the time of each response assessment will be measured including MCL-1 (anti-apoptotic) and summary statistics including the median and interquartile range of the change will be reported for all patients in the expansion cohort and also summarized for those achieving a CR/CRi and those patients who do not achieve a CR/CRi. This is based on section 9.1: We plan to collect bone marrow and peripheral blood samples at baseline, at the time of clinical response assessment and at the time of progression for correlative studies. These will be done in the laboratory of Dr. Marina Konopleva at MDACC and Dr. Tony Letai at DFCI. | 2 years |
| Change in expression of BCL-2 family proteins: BCL-2 homology 3 (BH3) | To measure expression and function of Bcl-2 family proteins and its modulation by venetoclax in ALL blasts. The change in expression of BCL-2 family proteins from baseline to the time of each response assessment will be measured including BCL-2 homology 3 (BH3) and summary statistics including the median and interquartile range of the change will be reported for all patients in the expansion cohort and also summarized for those achieving a CR/CRi and those patients who do not achieve a CR/CRi. This is based on section 9.1: We plan to collect bone marrow and peripheral blood samples at baseline, at the time of clinical response assessment and at the time of progression for correlative studies. These will be done in the laboratory of Dr. Marina Konopleva at MDACC and Dr. Tony Letai at DFCI. | 2 years |
| Change in expression of BCL-2 family proteins: BIM | To measure expression and function of Bcl-2 family proteins and its modulation by venetoclax in ALL blasts. The change in expression of BCL-2 family proteins from baseline to the time of each response assessment will be measured including BIM and summary statistics including the median and interquartile range of the change will be reported for all patients in the expansion cohort and also summarized for those achieving a CR/CRi and those patients who do not achieve a CR/CRi. This is based on section 9.1: We plan to collect bone marrow and peripheral blood samples at baseline, at the time of clinical response assessment and at the time of progression for correlative studies. These will be done in the laboratory of Dr. Marina Konopleva at MDACC and Dr. Tony Letai at DFCI. | 2 years |
| Change in expression of BCL-2 family proteins: BID | To measure expression and function of Bcl-2 family proteins and its modulation by venetoclax in ALL blasts. The change in expression of BCL-2 family proteins from baseline to the time of each response assessment will be measured including BID and summary statistics including the median and interquartile range of the change will be reported for all patients in the expansion cohort and also summarized for those achieving a CR/CRi and those patients who do not achieve a CR/CRi. This is based on section 9.1: We plan to collect bone marrow and peripheral blood samples at baseline, at the time of clinical response assessment and at the time of progression for correlative studies. These will be done in the laboratory of Dr. Marina Konopleva at MDACC and Dr. Tony Letai at DFCI. | 2 years |
| Change in expression of BCL-2 family proteins: BAD | To measure expression and function of Bcl-2 family proteins and its modulation by venetoclax in ALL blasts. The change in expression of BCL-2 family proteins from baseline to the time of each response assessment will be measured including BAD and summary statistics including the median and interquartile range of the change will be reported for all patients in the expansion cohort and also summarized for those achieving a CR/CRi and those patients who do not achieve a CR/CRi. This is based on section 9.1: We plan to collect bone marrow and peripheral blood samples at baseline, at the time of clinical response assessment and at the time of progression for correlative studies. These will be done in the laboratory of Dr. Marina Konopleva at MDACC and Dr. Tony Letai at DFCI. | 2 years |
| Change in expression of BCL-2 family proteins: NOXA | To measure expression and function of Bcl-2 family proteins and its modulation by venetoclax in ALL blasts. The change in expression of BCL-2 family proteins from baseline to the time of each response assessment will be measured including NOXA and summary statistics including the median and interquartile range of the change will be reported for all patients in the expansion cohort and also summarized for those achieving a CR/CRi and those patients who do not achieve a CR/CRi. This is based on section 9.1: We plan to collect bone marrow and peripheral blood samples at baseline, at the time of clinical response assessment and at the time of progression for correlative studies. These will be done in the laboratory of Dr. Marina Konopleva at MDACC and Dr. Tony Letai at DFCI. | 2 years |
| Change in expression of BCL-2 family proteins: PUMA | To measure expression and function of Bcl-2 family proteins and its modulation by venetoclax in ALL blasts. The change in expression of BCL-2 family proteins from baseline to the time of each response assessment will be measured including PUMA and summary statistics including the median and interquartile range of the change will be reported for all patients in the expansion cohort and also summarized for those achieving a CR/CRi and those patients who do not achieve a CR/CRi. This is based on section 9.1: We plan to collect bone marrow and peripheral blood samples at baseline, at the time of clinical response assessment and at the time of progression for correlative studies. These will be done in the laboratory of Dr. Marina Konopleva at MDACC and Dr. Tony Letai at DFCI. | 2 years |
| Change in expression of BCL-2 family proteins: HRK (pro-apoptotic) | To measure expression and function of Bcl-2 family proteins and its modulation by venetoclax in ALL blasts. The change in expression of BCL-2 family proteins from baseline to the time of each response assessment will be measured including HRK (pro-apoptotic) and summary statistics including the median and interquartile range of the change will be reported for all patients in the expansion cohort and also summarized for those achieving a CR/CRi and those patients who do not achieve a CR/CRi. This is based on section 9.1: We plan to collect bone marrow and peripheral blood samples at baseline, at the time of clinical response assessment and at the time of progression for correlative studies. These will be done in the laboratory of Dr. Marina Konopleva at MDACC and Dr. Tony Letai at DFCI. | 2 years |
| Boston |
| Massachusetts |
| 02114 |
| United States |
| Dana Farber Cancer Institute | Boston | Massachusetts | 02115 | United States |
| MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| Intermountain LDS Hospital | Salt Lake City | Utah | 84143 | United States |
| ID | Term |
|---|---|
| D007938 | Leukemia |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| C579720 | venetoclax |
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