Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Genentech, Inc. | INDUSTRY |
Not provided
Not provided
Not provided
This is a Phase 1, open-label, multicenter study evaluating the safety and PK profile of ABT-199 under a once daily dosing schedule. Two arms will be implemented for dose escalation: Arm A, CLL/SLL subjects and Arm B, NHL subjects. Arm A is designed to enroll approximately 116 subjects with relapsed or refractory CLL or SLL and Arm B is designed to enroll approximately 95 subjects with relapsed or refractory NHL. Fifty-six subjects were enrolled in Arm A and approximately 55 subjects will be enrolled in Arm B during the dose escalation portion of the study, with the objective of defining dose limiting toxicities (DLTs) and the MTD. Once the MTD is declared for the arm, approximately 60 additional CLL/SLL subjects in Arm A and approximately 20 additional DLBCL subjects and 20 additional follicular lymphoma subjects in Arm B will be enrolled in an expanded safety portion of the study at the recommended phase 2 dose (RPTD) and schedule.
Interventional Study Design - Primary Purpose: Determination of safety and tolerability.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ABT-199 | Drug | Arm A (Cohorts 1-8) and Arm B (Cohort 1-6): Subjects in dose escalation phase will receive 1 dose of ABT-199, followed by 6 days off drug, followed by continuous once daily dosing with ABT-199. Arm B (Cohorts 7+): Subjects in dose escalation phase will receive continuous once daily dosing with ABT-199. Arm A and Arm B: Subjects in expanded safety cohort will receive continuous once daily dosing with ABT-199. |
| Measure | Description | Time Frame |
|---|---|---|
| Determination of dose limiting toxicity (DLT), maximum tolerated dose (MTD), recommended phase two dose (RPTD), and lead-in period regimen | 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. | Lead-in period (2-5 weeks) plus 3 weeks of study drug administration at the designated cohort dose (continuous dosing) |
| Number of subjects with adverse events | First 16 weeks of study drug administration and every 4 weeks thereafter (continuous dosing for an anticipated maximum duration of 9 months) | |
| Determination of plasma peak concentration (Cmax) of ABT-199 | Blood and urine samples for pharmacokinetic analysis of ABT-199 will be collected at designated time points | Up to Week 24 for ABT-199 |
| Determination of trough concentration (Ctrough) of ABT-199 | Blood and urine samples for pharmacokinetic analysis of ABT-199 will be collected at designated time points | Up to Week 24 for ABT-199 |
| Determination of area under the concentration versus time curve (AUC) of ABT-199 | Blood and urine samples for pharmacokinetic analysis of ABT-199 will be collected at designated time points | Up to Week 24 for ABT-199 |
| Measure | Description | Time Frame |
|---|---|---|
| Food Effect - Cmax | Pharmacokinetic (PK) parameter Cmax (maximum plasma concentration of ABT-199) between each diet (ABT-199 under fasting versus low-fat, and fasting versus high-fat conditions (Cohorts 1-6 in Arm B subjects only) | Approximately 3 days |
| Preliminary efficacy assessment |
Not provided
Inclusion Criteria:
Subject must have either:
Subject has an Eastern Cooperative Oncology Group (ECOG) performance score less than or equal to 1.
Subject must have adequate bone marrow independent of growth factor support per local laboratory reference range at Screening.
Subject must have adequate coagulation, renal, and hepatic function, per laboratory reference range at Screening.
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| AbbVie Inc. | AbbVie | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Arizona Cancer Center - North Campus /ID# 52902 | Tucson | Arizona | 85719-1478 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28095146 | Background | Davids MS, Roberts AW, Seymour JF, Pagel JM, Kahl BS, Wierda WG, Puvvada S, Kipps TJ, Anderson MA, Salem AH, Dunbar M, Zhu M, Peale F, Ross JA, Gressick L, Desai M, Kim SY, Verdugo M, Humerickhouse RA, Gordon GB, Gerecitano JF. Phase I First-in-Human Study of Venetoclax in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma. J Clin Oncol. 2017 Mar 10;35(8):826-833. doi: 10.1200/JCO.2016.70.4320. Epub 2017 Jan 17. | |
| 34083230 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
Tumor response or clinical disease progression |
| Starting Week 4 for clinical disease progression and Week 6 for tumor response; and every 4 weeks thereafter (continuous dosing for an anticipated maximum duration of 9 months) |
| Minimal residual disease collection (MRD) | MRD assessed in the peripheral blood and/or bone marrow (BM) either by four color flow cytometry or ASO-PCR, will be measured in CLL subjects achieving CR/CRi. | At least 2 months after the CR, CRi criteria for tumor response are first met. Every 12 weeks thereafter, until MRD negativity has been achieved (in peripheral blood). |
| Food Effect - Tmax | Pharmacokinetic (PK) parameter Tmax (time to reach maximum plasma concentration of ABT-199) between each diet (ABT-199 under fasting versus low-fat, and fasting versus high-fat conditions (Cohorts 1-6 in Arm B subjects only) | Approximately 3 days |
| Food Effect - AUC | Pharmacokinetic (PK) parameter AUC (area under the concentration-time curve from time zero to hour 24 of ABT-199) between each diet (ABT-199 under fasting versus low-fat, and fasting versus high-fat conditions (Cohorts 1-6 in Arm B subjects only) | Approximately 3 days |
| Ucsd /Id# 48325 |
| La Jolla |
| California |
| 92093 |
| United States |
| Dana-Farber Cancer Institute /ID# 48324 | Boston | Massachusetts | 02215 | United States |
| Memorial Sloan Kettering Cancer Center /ID# 56810 | New York | New York | 10065-6007 | United States |
| University of Texas MD Anderson Cancer Center /ID# 48326 | Houston | Texas | 77030 | United States |
| Swedish Medical Center /ID# 135853 | Seattle | Washington | 98104 | United States |
| Fred Hutchinson Cancer Research /ID# 52882 | Seattle | Washington | 98109 | United States |
| Univ of Wisconsin Hosp/Clinics /ID# 56811 | Madison | Wisconsin | 53792-0001 | United States |
| Peter MacCallum Cancer Ctr /ID# 48323 | Melbourne | Victoria | 3000 | Australia |
| Royal Melbourne Hospital /ID# 48322 | Parkville | Victoria | 3050 | Australia |
| Derived |
| Davids MS, Roberts AW, Kenkre VP, Wierda WG, Kumar A, Kipps TJ, Boyer M, Salem AH, Pesko JC, Arzt JA, Mantas M, Kim SY, Seymour JF. Long-term Follow-up of Patients with Relapsed or Refractory Non-Hodgkin Lymphoma Treated with Venetoclax in a Phase I, First-in-Human Study. Clin Cancer Res. 2021 Sep 1;27(17):4690-4695. doi: 10.1158/1078-0432.CCR-20-4842. Epub 2021 Jun 3. |
| 31023700 | Derived | Roberts AW, Ma S, Kipps TJ, Coutre SE, Davids MS, Eichhorst B, Hallek M, Byrd JC, Humphrey K, Zhou L, Chyla B, Nielsen J, Potluri J, Kim SY, Verdugo M, Stilgenbauer S, Wierda WG, Seymour JF. Efficacy of venetoclax in relapsed chronic lymphocytic leukemia is influenced by disease and response variables. Blood. 2019 Jul 11;134(2):111-122. doi: 10.1182/blood.2018882555. Epub 2019 Apr 25. |
| 26639348 | Derived | Roberts AW, Davids MS, Pagel JM, Kahl BS, Puvvada SD, Gerecitano JF, Kipps TJ, Anderson MA, Brown JR, Gressick L, Wong S, Dunbar M, Zhu M, Desai MB, Cerri E, Heitner Enschede S, Humerickhouse RA, Wierda WG, Seymour JF. Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med. 2016 Jan 28;374(4):311-22. doi: 10.1056/NEJMoa1513257. Epub 2015 Dec 6. |
| ID | Term |
|---|---|
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D015448 | Leukemia, B-Cell |
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D008223 | Lymphoma |
Not provided
Not provided
| ID | Term |
|---|---|
| C579720 | venetoclax |
Not provided
Not provided
Not provided