| ID | Type | Description | Link |
|---|---|---|---|
| 2012-002038-34 | EudraCT Number |
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| Name | Class |
|---|---|
| AbbVie (prior sponsor, Abbott) | INDUSTRY |
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This multi-center, open-label, dose-finding study will evaluate the safety and pharmacokinetics as well as the preliminary efficacy of venetoclax (GDC-0199; ABT-199) administered in combination with obinutuzumab to participants with relapsed/refractory or previously untreated chronic lymphocytic leukemia (CLL). The study is comprised of two stages for each participant population: a dose-finding stage and a safety-expansion stage. The dose-finding stage will explore multiple doses of venetoclax to be used in combination with a fixed dose of obinutuzumab. The dose-finding stage will also explore two schedules for drug administration, Schedule A (venetoclax introduced before obinutuzumab) and Schedule B (venetoclax introduced after obinutuzumab).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose-Finding: Schedule A: Relapsed/Refractory CLL | Experimental | All 4 cohorts will begin venetoclax administration after the ramp-up period of 5 weeks. In 4 cohorts of participants with relapsed/refractory CLL escalating doses of venetoclax will be administered in combination with fixed dose obinutuzumab in the dose-finding stage. In Schedule A, venetoclax will be introduced before obinutuzumab. Schedule A will be explored prior to Schedule B. |
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| Dose-Finding: Schedule B: Relapsed/Refractory CLL | Experimental | In 4 cohorts of participants with relapsed/refractory CLL escalating doses of venetoclax will be administered in combination with fixed dose obinutuzumab in the dose-finding stage. In Schedule B, venetoclax will be introduced after obinutuzumab. Schedule A will be explored prior to Schedule B. |
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| Dose-Finding: Schedule A: Previously Untreated CLL | Experimental | All 4 cohorts will begin venetoclax administration after the ramp-up period of 5 weeks. In 4 cohorts of participants with previously untreated CLL escalating doses of venetoclax will be administered in combination with fixed dose obinutuzumab in the dose-finding stage. In Schedule A, venetoclax will be introduced before obinutuzumab. Schedule A will be explored prior to Schedule B. |
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| Dose-Finding: Schedule B: Previously Untreated CLL | Experimental | In 4 cohorts of participants with previously untreated CLL escalating doses of venetoclax will be administered in combination with fixed dose obinutuzumab in the dose-finding stage. In Schedule B, venetoclax will be introduced after obinutuzumab. Schedule A will be explored prior to Schedule B. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Obinutuzumab | Drug | Participants will receive IV infusion of obinutuzumab 100 milligrams (mg) on Day 1 of Cycle 1, 900 mg on Day 2 of Cycle 1, and 1000 mg on Days 8 and 15 of Cycle 1 and on Day 1 of Cycles 2-6. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Dose Limiting Toxicities (DLTs) | Schedule (Sch) A (Cycle 1 Day 1 to Day 21), Sch B (Cycle 1 Day 22 to Cycle 2 Day 28) (1 Cycle=28 days) | |
| Maximum Tolerated Dose (MTD) of Venetoclax in Combination with Obinutuzumab | Sch A (Cycle 1 Day 1 to Day 21), Sch B (Cycle 1 Day 22 to Cycle 2 Day 28) (1 Cycle=28 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants with Adverse Events | Baseline up to end of study (up to approximately 5 years and 5 months) | |
| Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to Obinutuzumab | Baseline up to Cycle 6 (1 Cycle=28 days) |
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Inclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Genentech, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSD Moores Cancer Center | La Jolla | California | 92093 | United States | ||
| Colorado Blood Cancer Institute (CBCI) at Presbyterian/ St. Luke's Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35708885 | Derived | Samineni D, Gibiansky L, Wang B, Vadhavkar S, Rajwanshi R, Tandon M, Sinha A, Al-Sawaf O, Fischer K, Hallek M, Salem AH, Li C, Miles D. Pharmacokinetics and Exposure-Response Analysis of Venetoclax + Obinutuzumab in Chronic Lymphocytic Leukemia: Phase 1b Study and Phase 3 CLL14 Trial. Adv Ther. 2022 Aug;39(8):3635-3653. doi: 10.1007/s12325-022-02170-w. Epub 2022 Jun 16. | |
| 30862645 |
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| Safety Expansion: Relapsed/Refractory CLL | Experimental | In participants with relapsed/refractory CLL a recommended dose of venetoclax will be administered in combination with obinutuzumab in the safety expansion stage. Schedule A or B will be used for the expansion cohort after a review of available safety data from the dose finding stage. |
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| Safety Expansion: Previously Untreated CLL | Experimental | In participants with previously untreated CLL a recommended dose of venetoclax will be administered in combination with obinutuzumab in the safety expansion stage. Schedule A or B will be used for the expansion cohort after a review of available safety data from the dose finding stage. |
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| Venetoclax | Drug | Participants will receive multiple doses of venetoclax orally once daily. |
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| Area Under the Concentration-Time Curve (AUC) of Venetoclax | Baseline up to Cycle 6 (1 Cycle=28 days) |
| Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax | Baseline up to Cycle 6 (1 Cycle=28 days) |
| Maximal Plasma Concentration (Cmax) of Venetoclax | Baseline up to Cycle 6 (1 Cycle=28 days) |
| Minimum Plasma Concentration (Cmin) of Venetoclax | Baseline up to Cycle 6 (1 Cycle=28 days) |
| Cmax of Obinutuzumab | Baseline up to Cycle 6 (1 Cycle=28 days) |
| Cmin of Obinutuzumab | Baseline up to Cycle 6 (1 Cycle=28 days) |
| Percentage of Participants with Confirmed Complete Response (CR) as Determined by Standard CLL Response Criteria | Baseline up to end of study (up to approximately 5 years and 5 months) |
| Percentage of Participants with Objective Response (Partial Response [PR] or CR [Including Cytopenic CR] as Determined by Standard CLL Response Criteria | Baseline up to end of study (up to approximately 5 years and 5 months) |
| Duration of Objective Response as Determined by Standard CLL Response Criteria | Baseline up to end of study (up to approximately 5 years and 5 months) |
| Overall Survival | Baseline up to death or end of study (up to approximately 5 years and 5 months) |
| Progression-Free Survival as Determined by Standard CLL Response Criteria | Baseline up to end of study (up to approximately 5 years and 5 months) |
| Change from Baseline in Number of B-Cells | Baseline up to end of study (up to approximately 5 years and 5 months) |
| Change from Baseline in Number of T-Cells | Baseline up to end of study (up to approximately 5 years and 5 months) |
| Change from Baseline in Number of Natural Killer (NK) Cells | Baseline up to end of study (up to approximately 5 years and 5 months) |
| Change from Baseline in Serum Immunoglobulin Level | Baseline up to end of study (up to approximately 5 years and 5 months) |
| Denver |
| Colorado |
| 80218 |
| United States |
| Weill Cornell Medical College-New York Presbyterian Hospital | New York | New York | 10021 | United States |
| Ohio State University Comprehensive Cancer Center | Columbus | Ohio | 43210 | United States |
| Oncology Associates of Oregon | Springfield | Oregon | 97477 | United States |
| SCRI-Tennessee Oncology | Nashville | Tennessee | 37203 | United States |
| The Methodist Hospital Research Institute; Academic Office of Clinical Trials | Houston | Texas | 77030 | United States |
| St James University Hospital | Leeds | LS9 7TF | United Kingdom |
| Leicester Royal Infirmary NHS Trust | Leicester | LE1 5WW | United Kingdom |
| Barts and The London School of Medicine and Dentistry; Queen Mary, University of London | London | E1 2AD | United Kingdom |
| Derived |
| Flinn IW, Gribben JG, Dyer MJS, Wierda W, Maris MB, Furman RR, Hillmen P, Rogers KA, Iyer SP, Quillet-Mary A, Ysebaert L, Walter HS, Verdugo M, Klein C, Huang H, Jiang Y, Lozanski G, Pignataro DS, Humphrey K, Mobasher M, Kipps TJ. Phase 1b study of venetoclax-obinutuzumab in previously untreated and relapsed/refractory chronic lymphocytic leukemia. Blood. 2019 Jun 27;133(26):2765-2775. doi: 10.1182/blood-2019-01-896290. Epub 2019 Mar 12. |
| ID | Term |
|---|---|
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| ID | Term |
|---|---|
| D015448 | Leukemia, B-Cell |
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| 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 |
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| ID | Term |
|---|---|
| C543332 | obinutuzumab |
| C579720 | venetoclax |
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