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| Name | Class |
|---|---|
| Genentech, Inc. | INDUSTRY |
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This is a Phase 1, open-label, multicenter study evaluating the safety, pharmacokinetic profile, and preliminary efficacy of ABT-199 in combination with Bendamustine/Rituximab in approximately 60 subjects with relapsed or refractory non-Hodgkin's lymphoma. This study will evaluate the safety and pharmacokinetic profile of ABT-199 in approximately 60 subjects when administered in combination with Bendamustine/Rituximab following a dose escalation scheme, with the objective of defining the dose limiting toxicity and the maximum tolerated dose.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1 | Experimental | Non-Hodgkin's Lymphoma (NHL) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ABT-199 | Drug | ABT-199 is taken orally once daily for 3 days out of each 28 day cycle. This is a dose escalation study, therefore the dose of ABT-199 will change throughout the study. |
| Measure | Description | Time Frame |
|---|---|---|
| Determination of the maximum tolerated dose of ABT-199 when administered with Bendamustine and Rituximab in subjects with relapsed or refractory non-Hodgkin's lymphoma | Protocol-defined events, which can not be attributed by the investigator to a clearly identifiable cause such as tumor progression, concurrent illness, or concomitant medication, will be considered a dose limiting toxicity | 3 days of study drug administration within the 28-day cycle at the designated cohort dose |
| Determination of peak concentration (Cmax), trough concentration (Ctrough) and/or area under the concentration versus time curve (AUC) of ABT-199, Bendamustine and Rituximab in the dose escalation cohort | Protocol-defined events, which can not be attributed by the investigator to a clearly identifiable cause such as tumor progression, concurrent illness, or concomitant medication, will be considered a dose limiting toxicity | Up to Cycle 6 for ABT-199 and Bendamustine, Up to Cycle 11 for Rituximab |
| Number of participants with adverse events as a measure of safety and tolerability | Adverse event monitoring, vital signs, physical examination, lymphocyte enumeration, 12-lead ECG, 2D echocardiogram/multiple gated acquisition scan (MUGA), and laboratory assessments | First 5 days of study drug administration, weekly through Cycle 2 and then Day 1 of each Cycle for an anticipated maximum duration of 6 months |
| Determination of the recommended Phase 2 dose of ABT-199 when administered with Bendamustine and Rituximab in subjects with relapsed or refractory non-Hodgkin's lymphoma | Protocol-defined events, which can not be attributed by the investigator to a clearly identifiable cause such as tumor progression, concurrent illness, or concomitant medication, will be considered a dose limiting toxicity | 3 days of study drug administration within the 28-day cycle at the designated cohort dose |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluate preliminary data regarding progression-free survival when ABT-199 is administered in combination with Bendamustine and Rituximab | Tumor response or clinical disease progression | Tumor Assessments: Approximately every 2 cycles through Cycle 17 then every 6 cycles thereafter; Clinical Disease Assessment: Weekly through Cycle 2, then every cycle thereafter |
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Inclusion Criteria:
Exclusion Criteria:
Subject has been diagnosed with Post-Transplant Lymphoproliferative Disease, Burkitt's lymphoma, Burkitt-like lymphoma, lymphoblastic lymphoma/leukemia, chronic lymphocytic leukemia, small lymphocytic lymphoma or mantle cell lymphoma (MCL).
Subject has refractory diffuse large B-cell lymphoma, defined as meeting any of the following criteria:
Subject has tested positive for human immunodeficiency virus (HIV).
Subject has a cardiovascular disability status of New York Heart Association Class greater or equal to 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity, results in fatigue, palpitations, dyspnea or anginal pain.
Subject has a significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, or hepatic disease that in the opinion of the Investigator would adversely affect his/her participating in this study.
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| Name | Affiliation | Role |
|---|---|---|
| AbbVie Inc. | AbbVie | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ucsd /Id# 67350 | La Jolla | California | 92093 | United States | ||
| University of California, Los Angeles /ID# 67343 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30060083 | Background | de Vos S, Swinnen LJ, Wang D, Reid E, Fowler N, Cordero J, Dunbar M, Enschede SH, Nolan C, Petrich AM, Ross JA, Salem AH, Verdugo M, Agarwal S, Zhou L, Kozloff M, Nastoupil LJ, Flowers CR. Venetoclax, bendamustine, and rituximab in patients with relapsed or refractory NHL: a phase Ib dose-finding study. Ann Oncol. 2018 Sep 1;29(9):1932-1938. doi: 10.1093/annonc/mdy256. |
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| Rituximab | Drug | Rituximab will be given by intravenous infusion for 1 day out of each 28 day cycle. |
|
| Bendamustine | Drug | Bendamustine will be given by intravenous infusion for 2 days out of each 28 day cycle. |
|
| Evaluate preliminary data regarding overall survival and duration of overall response when ABT-199 is administered in combination with Bendamustine and Rituximab. | Tumor response or clinical disease progression | Tumor Assessments: Approximately every 2 cycles through Cycle 17 then every 6 cycles thereafter; Clinical Disease Assessment: Weekly through Cycle 2, then every cycle thereafter |
| Evaluate preliminary data regarding objective response rate when ABT-199 is administered in combination with Bendamustine and Rituximab | Tumor response or clinical disease progression | Tumor Assessments: Approximately every 2 cycles through Cycle 17 then every 6 cycles thereafter; Clinical Disease Assessment: Weekly through Cycle 2, then every cycle thereafter |
| Evaluate preliminary data regarding time to tumor progression when ABT-199 is administered in combination with Bendamustine and Rituximab. | Tumor response or clinical disease progression | Tumor Assessments: Approximately every 2 cycles through Cycle 17 then every 6 cycles thereafter; Clinical Disease Assessment: Weekly through Cycle 2, then every cycle thereafter |
| Los Angeles |
| California |
| 90095 |
| United States |
| Emory University Hospital /ID# 67349 | Atlanta | Georgia | 30322 | United States |
| Georgia Regents University /ID# 67342 | Augusta | Georgia | 30912 | United States |
| Ingalls Memorial Hosp /ID# 67344 | Harvey | Illinois | 60426 | United States |
| Johns Hopkins University /ID# 67345 | Baltimore | Maryland | 21287 | United States |
| Henry Ford Health System /ID# 67346 | Detroit | Michigan | 48202 | United States |
| University of Texas MD Anderson Cancer Center /ID# 69222 | Houston | Texas | 77030 | United States |
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C579720 | venetoclax |
| D000069283 | Rituximab |
| D000069461 | Bendamustine Hydrochloride |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D002087 | Butyrates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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