[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT03319901":3,"trial-entities:NCT03319901":183,"trial-summary:NCT03319901":187},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":20,"study_type":21,"primary_purpose":22,"phases":23,"enrollment_info":26,"interventions":29,"primary_outcomes":42,"secondary_outcomes":47,"sex":94,"minimum_age":95,"maximum_age":96,"healthy_volunteers":97,"eligibility_criteria":98,"std_ages":131,"locations":134,"central_contacts":172,"overall_officials":173,"references":177,"see_also_links":182},"NCT03319901","16-648","Venetoclax and Chemotherapy as Frontline Therapy in Older Patients and Patients With Relapsed\u002FRefractory ALL","A Phase Ib Study of the Combination of Venetoclax With Chemotherapy as Frontline Therapy in Older Patients and Patients With Relapsed\u002FRefractory Acute Lymphoblastic Leukemia","ACTIVE_NOT_RECRUITING","2028-05-30","2026-05","2026-06-01","2017-10-30","Dana-Farber Cancer Institute","OTHER",true,"This research study is studying a medication called Venetoclax and a chemotherapy regimen as a possible treatment for Acute Lymphoblastic Leukemia.\n\nThe drugs involved in this study are:\n\n* Venetoclax\n* Standard Chemotherapy (which includes cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, 6-mercaptopurine, etoposide, and cytarabine","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.\n\nThe FDA (the U.S. Food and Drug Administration) has not approved Venetoclax for this specific disease, but it has been approved for other uses.\n\nVenetoclax is an inhibitor of Bcl-2. Bcl-2 is critical for keeping cancer cells alive.\n\nBy 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.\n\nIn 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.",[19],"Leukemia",[19],"INTERVENTIONAL","TREATMENT",[24,25],"PHASE1","PHASE2",{"count":27,"type":28},82,"ESTIMATED",[30,38],{"type":31,"name":32,"description":33,"armGroupLabels":34,"otherNames":36},"DRUG","Venetoclax","Venetoclax is an inhibitor of Bcl-2. Bcl-2 is critical for keeping cancer cells alive.\n\nBy inhibiting Bcl-2, venetoclax promotes cancer cell death.",[35],"Venetoclax + Chemotherapy",[37],"ABT199",{"type":31,"name":39,"description":40,"armGroupLabels":41},"Standard Chemotherapy","Standard treatment of chemotherapy is administered",[35],[43],{"measure":44,"description":45,"timeFrame":46},"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",[48,51,54,57,59,62,64,67,70,73,76,79,82,85,88,91],{"measure":49,"description":50,"timeFrame":46},"To Evaluate The Safety of the Combination","To evaluate the safety of this combination in a dose expansion cohort.\n\nThe proportion of patients having a grade 3 or higher adverse event will be estimated with a 95% confidence interval in the expansion cohort.",{"measure":52,"description":53,"timeFrame":46},"Complete Response","To determine the efficacy: complete response (CR) with incomplete marrow recovery (CRi) of venetoclax in combination with chemotherapy in patients with newly diagnosed ALL",{"measure":55,"description":56,"timeFrame":46},"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",{"measure":58,"description":56,"timeFrame":46},"Overall Survival",{"measure":60,"description":61,"timeFrame":46},"Minimal Residual Disease","To determine the rate of minimal residual disease (MRD) negativity in patients achieving CR\u002FCRi and its correlation with disease-free survival (DFS) and OS",{"measure":63,"description":61,"timeFrame":46},"Disease Free Survival",{"measure":65,"description":66,"timeFrame":46},"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.\n\nThe 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\u002FCRi and those patients who do not achieve a CR\u002FCRi.\n\nThis 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.",{"measure":68,"description":69,"timeFrame":46},"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.\n\nThe 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\u002FCRi and those patients who do not achieve a CR\u002FCRi.\n\nThis 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.",{"measure":71,"description":72,"timeFrame":46},"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.\n\nThe 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\u002FCRi and those patients who do not achieve a CR\u002FCRi.\n\nThis 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.",{"measure":74,"description":75,"timeFrame":46},"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.\n\nThe 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\u002FCRi and those patients who do not achieve a CR\u002FCRi.\n\nThis 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.",{"measure":77,"description":78,"timeFrame":46},"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.\n\nThe 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\u002FCRi and those patients who do not achieve a CR\u002FCRi.\n\nThis 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.",{"measure":80,"description":81,"timeFrame":46},"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.\n\nThe 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\u002FCRi and those patients who do not achieve a CR\u002FCRi.\n\nThis 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.",{"measure":83,"description":84,"timeFrame":46},"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.\n\nThe 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\u002FCRi and those patients who do not achieve a CR\u002FCRi.\n\nThis 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.",{"measure":86,"description":87,"timeFrame":46},"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.\n\nThe 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\u002FCRi and those patients who do not achieve a CR\u002FCRi.\n\nThis 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.",{"measure":89,"description":90,"timeFrame":46},"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.\n\nThe 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\u002FCRi and those patients who do not achieve a CR\u002FCRi.\n\nThis 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.",{"measure":92,"description":93,"timeFrame":46},"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.\n\nThe 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\u002FCRi and those patients who do not achieve a CR\u002FCRi.\n\nThis 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.","ALL","18 Years",null,false,{"inclusion":99,"exclusion":113,"raw_text":130},[100,101,102,103,104,105,106,107,108,109,110,111,112],"Patients with previously untreated acute lymphoblastic leukemia (B-cell or T-cell)","Bone marrow involvement with ≥20% lymphoblasts","Age ≥ 60 Years","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","Serum total bilirubin ≤1.5 x upper limit of normal (ULN) or ≤3 x ULN for patients with Gilbert's disease","Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 x ULN, unless clearly due to disease involvement","Creatinine clearance \\>50 mL\u002Fmin (calculated according to institutional standards or using Cockcroft-Gault or Modification of Diet in Renal Disease (MDRD) formula)","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",[114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129],"Ph-positive ALL, Burkitt's leukemia\u002Flymphoma, or lymphoblastic lymphoma","Patient is pregnant or breastfeeding","Patients with uncontrolled infection","Hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV)","Major surgery or radiation therapy within 4 weeks prior to the first study dose","Systemic chemotherapy\u002Fradiotherapy\u002Finvestigational therapy within 14 days (with the exception of hydroxyurea and\u002For dexamethasone, or one dose of cytarabine) prior to starting therapy","Symptomatic or untreated leptomeningeal disease or spinal cord compression","Patients with active heart disease (New York Heart Association (NYHA) class 3-4 as assessed by history and physical examination, unstable angina\u002Fstroke\u002Fmyocardial infarction within the last 6 months)","Patients with a cardiac ejection fraction (as measured by either Multi Gated Acquisition (MUGA) or echocardiogram (EKG)) \\\u003C40%","History of another primary invasive malignancy that has not been definitively treated or in remission for at least 2 years. Patients with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses)","Concurrent use of warfarin","Received Cytochrome P450 3A (CYP3A) inhibitors (such as fluconazole, ketoconazole, voriconazole, and clarithromycin) within 3 days of starting venetoclax; received strong CYP3A inducers (such as rifampin, rifabutin, phenytoin, carbamazepine, and St. John's Wort) within 3 days of starting venetoclax","Consumed grapefruit, grapefruit products, Seville oranges, or star fruit within 3 days prior to starting venetoclax","Prior treatment with venetoclax","Malabsorption syndrome or other conditions that preclude enteral route of administration","Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and\u002For would make the patient inappropriate for enrollment into this study","Inclusion Criteria:\n\n* Patients with previously untreated acute lymphoblastic leukemia (B-cell or T-cell)\n* Bone marrow involvement with ≥20% lymphoblasts\n* Age ≥ 60 Years\n\nOR\n\n* Patients with relapsed or refractory acute lymphoblastic leukemia (B-cell or T-cell) defined as receiving one or more cytotoxic containing regimens\n* Bone marrow involvement with ≥5% lymphoblasts\n* Age ≥ 18 Years\n* Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Refer to Appendix D)\n* Adequate organ function\n\n  * Serum total bilirubin ≤1.5 x upper limit of normal (ULN) or ≤3 x ULN for patients with Gilbert's disease\n  * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 x ULN, unless clearly due to disease involvement\n  * Creatinine clearance \\>50 mL\u002Fmin (calculated according to institutional standards or using Cockcroft-Gault or Modification of Diet in Renal Disease (MDRD) formula)\n* 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\n* Patients or their legally authorized representative must provide written informed consent\n\nExclusion Criteria:\n\n* Ph-positive ALL, Burkitt's leukemia\u002Flymphoma, or lymphoblastic lymphoma\n* Patient is pregnant or breastfeeding\n* Patients with uncontrolled infection\n* Hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV)\n* Major surgery or radiation therapy within 4 weeks prior to the first study dose\n* Systemic chemotherapy\u002Fradiotherapy\u002Finvestigational therapy within 14 days (with the exception of hydroxyurea and\u002For dexamethasone, or one dose of cytarabine) prior to starting therapy\n* Symptomatic or untreated leptomeningeal disease or spinal cord compression\n* Patients with active heart disease (New York Heart Association (NYHA) class 3-4 as assessed by history and physical examination, unstable angina\u002Fstroke\u002Fmyocardial infarction within the last 6 months)\n* Patients with a cardiac ejection fraction (as measured by either Multi Gated Acquisition (MUGA) or echocardiogram (EKG)) \\\u003C40%\n* History of another primary invasive malignancy that has not been definitively treated or in remission for at least 2 years. Patients with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses)\n* Concurrent use of warfarin\n* Received Cytochrome P450 3A (CYP3A) inhibitors (such as fluconazole, ketoconazole, voriconazole, and clarithromycin) within 3 days of starting venetoclax; received strong CYP3A inducers (such as rifampin, rifabutin, phenytoin, carbamazepine, and St. John's Wort) within 3 days of starting venetoclax\n* Consumed grapefruit, grapefruit products, Seville oranges, or star fruit within 3 days prior to starting venetoclax\n* Prior treatment with venetoclax\n* Malabsorption syndrome or other conditions that preclude enteral route of administration\n* Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and\u002For would make the patient inappropriate for enrollment into this study",[132,133],"ADULT","OLDER_ADULT",[135,144,152,156,164],{"facility":136,"city":137,"state":138,"zip":139,"country":140,"geoPoint":141},"University of Chicago","Chicago","Illinois","60637","United States",{"lat":142,"lon":143},41.85003,-87.65005,{"facility":145,"city":146,"state":147,"zip":148,"country":140,"geoPoint":149},"Massachusetts General Hospital","Boston","Massachusetts","02114",{"lat":150,"lon":151},42.35843,-71.05977,{"facility":153,"city":146,"state":147,"zip":154,"country":140,"geoPoint":155},"Dana Farber Cancer Institute","02115",{"lat":150,"lon":151},{"facility":157,"city":158,"state":159,"zip":160,"country":140,"geoPoint":161},"MD Anderson Cancer Center","Houston","Texas","77030",{"lat":162,"lon":163},29.76328,-95.36327,{"facility":165,"city":166,"state":167,"zip":168,"country":140,"geoPoint":169},"Intermountain LDS Hospital","Salt Lake City","Utah","84143",{"lat":170,"lon":171},40.76078,-111.89105,[],[174],{"name":175,"affiliation":13,"role":176},"Marlise Luskin, MD, MSCE","PRINCIPAL_INVESTIGATOR",[178],{"pmid":179,"type":180,"citation":181},"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\u002Fbloodadvances.2024014405.",[],{"nct_id":4,"conditions":184,"biomarkers":186},[185],"Acute Lymphoblastic Leukemia",[],{"nct_id":4,"found":15,"summary":188,"prompt_version":198},{"design":189,"status":190,"heading":191,"summary":192,"follow_up":193,"word_count":194,"commitments":195,"compensation":196,"drugs_mentioned":197},"This is a Phase 1 interventional study, which means it tests the safety and appropriate dose of Venetoclax and chemotherapy. It plans to enroll 82 participants.","completed","Venetoclax and Chemotherapy for Acute Lymphoblastic Leukemia","This study is testing Venetoclax, a medication that helps kill cancer cells by blocking a protein called Bcl-2, when given with standard chemotherapy. It's for people with Acute Lymphoblastic Leukemia (ALL), specifically those aged 60 or older who haven't had treatment before, or those aged 18 or older whose ALL has come back or hasn't responded to previous treatments. The main goal is to find the safest and most effective dose of Venetoclax when combined with chemotherapy. This is a Phase 1 study, meaning it's focused on safety and finding the right dose. The study is currently recruiting 82 participants.","The maximum tolerated dose will be measured at 2 years.",100,"Not specified in the trial record.","Not stated in the trial record.",[32,39],"v2"]