Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
ABT-199 · 8 trials · 9 indications
The objective remission rate (ORR) was defined as the percentage of participants who achieved complete remission (CR), complete remission with incomplete bone marrow recovery (CRi), or partial remission (PR) per the International Working Group criteria for AML. Complete remission (CR) was defined as peripheral neutrophils at least 10˄3/μL, platelets ≥ 10˄5/μL and normocellular bone marrow with ≤ 5% blasts. Complete remission with incomplete bone marrow recovery (CRi) was defined as bone marrow with less than 5% blasts, with peripheral neutrophils of at least 10˄3/μL or platelets ≥ 10˄5/μL. Partial remission (PR) was defined as normalization in peripheral blood neutrophil and platelet counts with at least a 50% decrease in blasts persisting in bone marrow versus baseline.
Electrocardiogram and Multi Gated Acquisition Scan and/or Echocardiogram
Subjects will be monitored for clinical and laboratory evidence of adverse events throughout the study
Chemistry, coagulation, hematology, lymphocyte enumeration, paraproteins, urinalysis, and, if appropriate, viral polymerase chain reaction and viral serologies
Subjects will be monitored for clinical and laboratory evidence of adverse events throughout the study
Body temperature, weight, blood pressure, heart rate
Blood samples for pharmacokinetic (PK) analysis of ABT-199 will be collected at designated timepoints to assess the PK parameters for ABT-199 alone relative to ABT-199 with ketoconazole
Blood samples for pharmacokinetic analysis of ABT-199 will be collected at designated timepoints
ABT-199 will be dose-escalated until the largest dose is reached that is determined to be safe based on adverse event reporting and dose-limiting toxicities information from all subjects.
Collect all adverse events at each visit.
Blood samples for pharmacokinetic analysis of ABT-199 will be collected at designated timepoints
Blood samples for pharmacokinetic analysis of ABT-199 will be collected at designated timepoints
ABT-199 will be dose-escalated until the largest dose is reached that is determined to be safe based on adverse event reporting and dose-limiting toxicities information from all subjects.
Blood pressure, heart rate and body temperature
Hematology, Chemistry, and Urinalysis
ECGs done in triplicate
Cmax
Time to Cmax
the area under the exposure-time curve of ABT-199 extrapolated to infinite time for single doses and up to 24 hrs for multiple doses of ABT-199
Protocol-defined events, which are attributed as having a reasonable possibility of being related to the administration of ABT-199 and/or rituximab, or can not be attributed by the investigator to a clearly identifiable cause such as tumor progression, concurrent illness, underlying disease or concomitant medication, will be considered a dose limiting toxicity.
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
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
Adverse event monitoring, vital signs, physical examination, lymphocyte enumeration, 12-lead ECG, 2D echocardiogram/multiple gated acquisition scan (MUGA), and laboratory assessments
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
Protocol-defined events, which can not be attributed by the investigator to a clearly identifiable cause such as tumor progression, underlying illness, concurrent illness, or concomitant medication, will be considered a DLT. Dose limiting toxicities of tumor lysis syndrome observed during the lead-in period will be attributed to the lead-in period.
Blood and urine samples for pharmacokinetic analysis of ABT-199 will be collected at designated time points
| Arm | Type | Description |
|---|---|---|
| ABT-199 | EXPERIMENTAL | Continuous dosing of venetoclax (ABT-199) QD (once daily) beginning with dose-escalation on Week 1 Day 1. Participants received a dose of 20 mg of ABT-199 on Week 1 Day 1, 50 mg on Day 2, 100 mg on Day 3, 200 mg on Day 4, 400 mg on Day 5, 800 mg on Day 6 and QD thereafter. |
| Arm A (ABT-199 and ketoconazole) | EXPERIMENTAL | - |
| ABT-199 + BTZ/Dex Dose Escalation Cohorts | EXPERIMENTAL | Evaluate the safety and pharmacokinetics profile of ABT-199 administered with standard therapy bortezomib and dexamethasone in a dose escalation scheme in approximately 54 subjects. |
| ABT-199 + BTZ/Dex Safety Expansion Cohort | EXPERIMENTAL | Safety expansion cohort to further evaluate recommended phase two dose (RPTD) of ABT-199 administered with standard therapy bortezomib and dexamethasone in approximately 12 subjects. |
| Single Dose | EXPERIMENTAL | Subjects enrolled in the Single Ascending Dose (SAD) part of the study will receive a single dose of study drug or placebo. (Groups 1, 2, 3, 4, 5 and 6). |
| Multiple Dose | EXPERIMENTAL | Subjects enrolled in the Multiple Ascending Dose (MAD) part of the study will receive multiple doses of study drug or placebo. (Groups 7, 8, 9, 10 and 11) |
| Arm 1 | EXPERIMENTAL | Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL) |
| Arm A (CLL/SLL subjects) | EXPERIMENTAL | Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) subjects |
| Arm B (NHL subjects) | EXPERIMENTAL | Non-Hodgkin lymphoma (NHL) subjects |
| Name | Type | Description |
|---|---|---|
| ABT-199 | DRUG | Tablet |
| Ketoconazole | DRUG | Subjects will be dosed with ABT-199, then dosed with ABT-199 in combination with ketoconazole |
| bortezomib | DRUG | Bortezomib at cohort-defined dosing schedules and dose levels. Bortezomib at defined dose and schedule for Safety Expansion cohort |
| dexamethasone | DRUG | Dexamethasone at cohort-defined dosing schedules and dose levels. Dexamethasone at defined dose and schedule for Safety Expansion cohort. |
| Placebo | OTHER | Tablet |
| Rituximab | DRUG | Rituximab will be given by intravenous infusion on day 1 of Months 1, 2, 3, 4, 5, and 6. May be reinitiated for an additional 6 months. |
| Bendamustine | DRUG | Bendamustine will be given by intravenous infusion for 2 days out of each 28 day cycle. |
Inclusion Criteria: 1. Histological or cytological confirmation of relapsed or refractory acute myelogenous leukemia (AML) (by World Health Organization \[WHO\] classification) or untreated AML in participants who are unfit for intensive therapy. 2. Participant has an Eastern Cooperative Oncology G...
ABT-199 is an investigational small molecule being studied for use in several blood cancers and autoimmune conditions, including chronic lymphocytic leukemia, non-Hodgkin lymphoma, small lymphocytic lymphoma, mantle-cell lymphoma, acute myelogenous leukemia, and lupus erythematosus. It is being developed by AbbVie Inc. and is currently in Phase 2 clinical development.
ABT-199 is being developed by AbbVie Inc., a biopharmaceutical company traded on the New York Stock Exchange under the ticker ABBV. The drug is an investigational small molecule in Phase 2 clinical development for oncology and autoimmune indications.
ABT-199 is in Phase 2 clinical development. It is an investigational drug and has not been approved by the FDA. The drug is being studied for multiple conditions, including chronic lymphocytic leukemia, non-Hodgkin lymphoma, and lupus erythematosus.
ABT-199 has completed three Phase 1 clinical trials. NCT01328626 evaluated safety and pharmacokinetics in 222 patients with relapsed or refractory chronic lymphocytic leukemia and non-Hodgkin lymphoma. NCT01682616 studied ABT-199 in combination with rituximab in 49 patients with relapsed chronic lymphocytic leukemia and small lymphocytic lymphoma. NCT01686555 evaluated the drug in 97 female patients with systemic lupus erythematosus.
Yes, ABT-199 is being studied in mantle-cell lymphoma. A completed Phase 1 trial, NCT02419560, evaluated optimal dosing of ABT-199 in combination with ibrutinib in 37 patients with recurrent mantle-cell lymphoma. The trial was conducted in the United States.
ABT-199 has been studied in lupus erythematosus. A completed Phase 1 trial, NCT01686555, evaluated the safety, tolerability, and pharmacokinetics of ABT-199 in 97 female patients with systemic lupus erythematosus. The trial was conducted in the United States, Germany, Mexico, and Puerto Rico.