Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

A Study of Venetoclax in Combination With Bendamustine + Rituximab or Bendamustine + Obinutuzumab in Participants With Relapsed/Refractory or Previously Untreated Chronic Lymphocytic Leukemia (CLL)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2016 by Genentech, Inc.
Sponsor:
Collaborator:
AbbVie (prior sponsor, Abbott)
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01671904
First received: August 10, 2012
Last updated: November 1, 2016
Last verified: November 2016
  Purpose
This multi-center, open-label, dose-finding study will evaluate the safety and pharmacokinetics of venetoclax (GDC-0199, ABT-199) administered in combination with bendamustine and rituximab (BR) (MabThera/Rituxan) or bendamustine and obinutuzumab (BG) to participants with relapsed/refractory or previously untreated CLL. The study will explore two schedules for drug administration, Schedule A (venetoclax introduced before other agents) and Schedule B (introduced after other agents). In addition, the study will explore two venetoclax combination regimens: venetoclax+BR and venetoclax + BG (the latter is optional). 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 fixed doses of BR or BG.

Condition Intervention Phase
Chronic Lymphocytic Leukemia
Drug: Bendamustine
Drug: Obinutuzumab
Drug: Rituximab
Drug: Venetoclax
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase IB, Open-Label Study Evaluating the Safety and Pharmacokinetics of Venetoclax (GDC-0199, ABT-199) in Combination With Bendamustine+Rituximab (BR) or Bendamustine+Obinutuzumab (BG) in Patients With Relapsed/Refractory or Previously Untreated Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Maximum Tolerated Dose [ Time Frame: Schedule (Sch) A (Cycle [Cy] 1 Day [D] 1 to Cy1D21), Sch B (Cy1D21 to Cy2D28) (Cy length = 28 days) ] [ Designated as safety issue: No ]
  • Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: Sch A (Cy1D1 to Cy1D21), Sch B (Cy1D21 to Cy2D28) (Cy length = 28 days) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetics (Plasma): Minimum Plasma Concentration (Cmin) of Venetoclax [ Time Frame: Sch A: Prd (0 h) on D 1 of Week 1-5; prd (0 h) on D1 of Cy (1 Cy=28 day) 1,2,4,6 and on Cy1D3; Sch B: Prd (0 h) on D1 of Cy1,3,4,6; prd (0 h) on Cy1D22, D1, 8, 15, 22 of Cy2 ] [ Designated as safety issue: No ]
  • Pharmacokinetics (Plasma): Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax [ Time Frame: Sch A: Prd (0 h), 8 h psd on D1 of Week 1-5; prd (0h) on D1 of Cy1,2,4,6, Cy1D3; 2,4,6,8h psd; Sch B: Prd (0h) on D1 of Cy1,2,3,4,6, Cy1D22, D8,15,22 of Cy2 (1 Cy=28 day); 8h psd on Cy1D22, D1,8,15,22 of Cy2; Cy3D1:2,4,6,8h psd ] [ Designated as safety issue: No ]
  • Pharmacokinetics (Serum): Cmax of Rituximab [ Time Frame: Sch A and B: Prd (0 h), end of infusion (EOI) on D1 of Cy1, 2; prd (0 h) on D1 of Cy4, 6 and 4 weeks after Cy6D1; Prd (0 h) of Cy3D1 of Sch B (1 Cy=28 days) ] [ Designated as safety issue: No ]
  • Pharmacokinetics (Serum): Cmin of Rituximab [ Time Frame: Sch A and B: Prd (0 h), EOI on D1 of Cy1, 2; prd (0 h) on D1 of Cy4, 6 and 4 weeks after Cy6D1; Prd (0 h) of Cy3D1 of Sch B (1 Cy=28 days) ] [ Designated as safety issue: No ]
  • Pharmacokinetics (Serum): Cmax of Obinutuzumab [ Time Frame: Sch A: Prd (0 h), EOI on D1,2,8,15 of Cy1, Cy2D1; prd (0 h) on Cy1D3, Cy3D1, D1 of Cy4, 5, 6 and 4 weeks after Cy6D1; Sch B: Prd (0 h), EOI on D1,2,8,15 of Cy1, D1 of Cy2, 3, 4, 5, 6; Prd (0 h) of Cy1D22; 4 weeks after Cy6D1 (1 Cy=28 days) ] [ Designated as safety issue: No ]
  • Pharmacokinetics (Serum): Cmin of Obinutuzumab [ Time Frame: Sch A: Prd (0 h) on D1,2,8,15 of Cy1, D1 of Cy2, Cy1D3, Cy3D1, D1 of Cy4, 5, 6; Sch B: Prd (0 h) on D1,2,8,15 of Cy1, D1 of Cy2, 3, 4, 5, 6, on D22 of Cy1 (1 Cy=28 days) ] [ Designated as safety issue: No ]
  • Pharmacokinetics (Plasma): Cmax of Bendamustine [ Time Frame: Sch A: Prd (0 h), EOI on Cy1D2; Sch B: Prd (0 h), EOI on Cy1D2, Cy3D2 (1 Cy=28 days) ] [ Designated as safety issue: No ]
  • Pharmacokinetics (Plasma): Cmin of Bendamustine [ Time Frame: Sch A: Prd (0 h) on Cy1D2; Sch B: Prd (0 h) on Cy1D2, Cy3D2 (1 Cy=28 days) ] [ Designated as safety issue: No ]
  • Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) According to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 Guidelines [ Time Frame: Baseline up to approximately 5.75 years ] [ Designated as safety issue: No ]
  • Duration of Response According to IWCLL 2008 Guidelines [ Time Frame: Baseline up to approximately 5.75 years ] [ Designated as safety issue: No ]
  • Pharmacokinetics (Plasma): Area Under the Concentration-Time Curve (AUC) of Venetoclax [ Time Frame: Sch A:Predose (prd[0 h]), 8 hour (h) postdose (psd) on D1 of Week 1-5; prd(0h) on D1 of Cy1,2,4,6, Cy1D3; 2,4,6,8h psd; Sch B:Prd(0h) on D1 of Cy1,2,3,4,6, Cy1D22, D8,15,22 of Cy2 (1 Cy=28 day); 8h psd on Cy1D22, D1,8,15,22 of Cy2; Cy3D1:2,4,6,8h psd ] [ Designated as safety issue: No ]
  • Pharmacokinetics (Plasma): Maximum Plasma Concentration (Cmax) of Venetoclax [ Time Frame: Sch A: Prd (0 h), 8 h psd on D1 of Week 1-5; prd (0h) on D1 of Cy1,2,4,6, Cy1D3; 2,4,6,8h psd; Sch B: Prd (0h) on D1 of Cy1,2,3,4,6, Cy1D22, D8,15,22 of Cy2 (1 Cy=28 day); 8h psd on Cy1D22, D1,8,15,22 of Cy2; Cy3D1:2,4,6,8h psd ] [ Designated as safety issue: No ]
  • Number of Participants With Adverse Events [ Time Frame: Up to approximately 5.75 years ] [ Designated as safety issue: No ]
  • Percentage of Participants with CR, Assessed With the use of Computed tomography (CT) Scanning [ Time Frame: Baseline up to approximately 5.75 years ] [ Designated as safety issue: No ]
  • Progression-Free Survival (PFS) According to IWCLL 2008 Guidelines [ Time Frame: Baseline up to approximately 5.75 years ] [ Designated as safety issue: No ]
  • Overall Survival (OS) [ Time Frame: Baseline up to approximately 5.75 years ] [ Designated as safety issue: No ]
  • Change From Baseline in B-Cells [ Time Frame: Baseline up to approximately 5.75 years ] [ Designated as safety issue: No ]
  • Change From Baseline in T-Cells [ Time Frame: Baseline up to approximately 5.75 years ] [ Designated as safety issue: No ]
  • Change From Baseline in Natural Killer (NK) Cells [ Time Frame: Baseline up to approximately 5.75 years ] [ Designated as safety issue: No ]
  • Change From Baseline in Serum Immunoglobulin [ Time Frame: Baseline up to approximately 5.75 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: January 2014
Estimated Study Completion Date: May 2020
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose-Finding: Schedule A (Optional): CLL
Optional study arm: In four cohorts of participants with relapsed/refractory or previously untreated CLL escalating doses of venetoclax will be administered in combination with fixed dose bendamustine and obinutuzumab in the dose-finding stage. In Schedule A, venetoclax will be introduced before bendamustine and obinutuzumab. Schedule A will be explored prior to Schedule B.
Drug: Bendamustine
Participants will receive intravenous (IV) infusion of bendamustine (90 or 70 milligrams per square meter [mg/m^2]) on Days 2-3 of Cycle 1 and Days 1-2 of Cycles 2-6.
Drug: Obinutuzumab
Participants will receive IV infusion of obinutuzumab (100 milligrams [mg]) on Day 1 of Cycle 1; 900 mg administered on Day 2 of Cycle 1; and 1000 mg administered on Days 8 and 15 of Cycle 1 and on Day 1 of Cycles 2-6.
Other Name: GA101; RO5072759
Drug: Venetoclax
Participants will receive multiple doses of venetoclax orally once daily.
Other Name: ABT-199; GDC-0199
Experimental: Dose-Finding: Schedule A: Previously Untreated CLL
In four cohorts of participants with previously untreated CLL escalating doses of venetoclax will be administered in combination with fixed dose bendamustine and rituximab in the dose-finding stage. In Schedule A, venetoclax will be introduced before bendamustine and rituximab. Schedule A will be explored prior to Schedule B.
Drug: Bendamustine
Participants will receive intravenous (IV) infusion of bendamustine (90 or 70 milligrams per square meter [mg/m^2]) on Days 2-3 of Cycle 1 and Days 1-2 of Cycles 2-6.
Drug: Rituximab
Participants will receive IV infusion of rituximab (375 mg/m^2) on Day 1 of Cycle 1 and 500 mg/m^2 administered on Day 1 of Cycles 2-6.
Other Name: MabThera; Rituxan
Drug: Venetoclax
Participants will receive multiple doses of venetoclax orally once daily.
Other Name: ABT-199; GDC-0199
Experimental: Dose-Finding: Schedule A: Relapsed/Refractory CLL
In four cohorts of participants with relapsed/refractory CLL escalating doses of venetoclax will be administered in combination with fixed dose bendamustine and rituximab in the dose-finding stage. In Schedule A, venetoclax will be introduced before bendamustine and rituximab. Schedule A will be explored prior to Schedule B.
Drug: Bendamustine
Participants will receive intravenous (IV) infusion of bendamustine (90 or 70 milligrams per square meter [mg/m^2]) on Days 2-3 of Cycle 1 and Days 1-2 of Cycles 2-6.
Drug: Rituximab
Participants will receive IV infusion of rituximab (375 mg/m^2) on Day 1 of Cycle 1 and 500 mg/m^2 administered on Day 1 of Cycles 2-6.
Other Name: MabThera; Rituxan
Drug: Venetoclax
Participants will receive multiple doses of venetoclax orally once daily.
Other Name: ABT-199; GDC-0199
Experimental: Dose-Finding: Schedule B (Optional): CLL
Optional study arm: In four cohorts of participants with relapsed/refractory or previously untreated CLL escalating doses of venetoclax will be administered in combination with fixed dose bendamustine and obinutuzumab in the dose-finding stage. In Schedule B, venetoclax will be introduced after bendamustine and obinutuzumab. Schedule A will be explored prior to Schedule B.
Drug: Bendamustine
Participants will receive intravenous (IV) infusion of bendamustine (90 or 70 milligrams per square meter [mg/m^2]) on Days 2-3 of Cycle 1 and Days 1-2 of Cycles 2-6.
Drug: Obinutuzumab
Participants will receive IV infusion of obinutuzumab (100 milligrams [mg]) on Day 1 of Cycle 1; 900 mg administered on Day 2 of Cycle 1; and 1000 mg administered on Days 8 and 15 of Cycle 1 and on Day 1 of Cycles 2-6.
Other Name: GA101; RO5072759
Drug: Venetoclax
Participants will receive multiple doses of venetoclax orally once daily.
Other Name: ABT-199; GDC-0199
Experimental: Dose-Finding: Schedule B: Previously Untreated CLL
In four cohorts of participants with previously untreated CLL escalating doses of venetoclax will be administered in combination with fixed dose bendamustine and rituximab in the dose-finding stage. In Schedule B, venetoclax will be introduced after bendamustine and rituximab. Schedule A will be explored prior to Schedule B.
Drug: Bendamustine
Participants will receive intravenous (IV) infusion of bendamustine (90 or 70 milligrams per square meter [mg/m^2]) on Days 2-3 of Cycle 1 and Days 1-2 of Cycles 2-6.
Drug: Rituximab
Participants will receive IV infusion of rituximab (375 mg/m^2) on Day 1 of Cycle 1 and 500 mg/m^2 administered on Day 1 of Cycles 2-6.
Other Name: MabThera; Rituxan
Drug: Venetoclax
Participants will receive multiple doses of venetoclax orally once daily.
Other Name: ABT-199; GDC-0199
Experimental: Dose-Finding: Schedule B: Relapsed/Refractory CLL
In four cohorts of participants with relapsed/refractory CLL escalating doses of venetoclax will be administered in combination with fixed dose bendamustine and rituximab in the dose-finding stage. In Schedule B, venetoclax will be introduced after bendamustine and rituximab. Schedule A will be explored prior to Schedule B.
Drug: Bendamustine
Participants will receive intravenous (IV) infusion of bendamustine (90 or 70 milligrams per square meter [mg/m^2]) on Days 2-3 of Cycle 1 and Days 1-2 of Cycles 2-6.
Drug: Rituximab
Participants will receive IV infusion of rituximab (375 mg/m^2) on Day 1 of Cycle 1 and 500 mg/m^2 administered on Day 1 of Cycles 2-6.
Other Name: MabThera; Rituxan
Drug: Venetoclax
Participants will receive multiple doses of venetoclax orally once daily.
Other Name: ABT-199; GDC-0199
Experimental: Safety Expansion (Optional): Previously Untreated CLL
In participants with previously untreated CLL a recommended dose of venetoclax will be administered in combination with bendamustine and obinutuzumab in the safety expansion stage.
Drug: Bendamustine
Participants will receive intravenous (IV) infusion of bendamustine (90 or 70 milligrams per square meter [mg/m^2]) on Days 2-3 of Cycle 1 and Days 1-2 of Cycles 2-6.
Drug: Obinutuzumab
Participants will receive IV infusion of obinutuzumab (100 milligrams [mg]) on Day 1 of Cycle 1; 900 mg administered on Day 2 of Cycle 1; and 1000 mg administered on Days 8 and 15 of Cycle 1 and on Day 1 of Cycles 2-6.
Other Name: GA101; RO5072759
Drug: Venetoclax
Participants will receive multiple doses of venetoclax orally once daily.
Other Name: ABT-199; GDC-0199
Experimental: Safety Expansion: Previously Untreated CLL
In participants with previously untreated CLL a recommended dose of venetoclax will be administered in combination with bendamustine and rituximab in the safety expansion stage.
Drug: Bendamustine
Participants will receive intravenous (IV) infusion of bendamustine (90 or 70 milligrams per square meter [mg/m^2]) on Days 2-3 of Cycle 1 and Days 1-2 of Cycles 2-6.
Drug: Rituximab
Participants will receive IV infusion of rituximab (375 mg/m^2) on Day 1 of Cycle 1 and 500 mg/m^2 administered on Day 1 of Cycles 2-6.
Other Name: MabThera; Rituxan
Drug: Venetoclax
Participants will receive multiple doses of venetoclax orally once daily.
Other Name: ABT-199; GDC-0199
Experimental: Safety Expansion: Relapsed/Refractory CLL
In participants with relapsed/refractory CLL a recommended dose of venetoclax will be administered in combination with bendamustine and rituximab in the safety expansion stage.
Drug: Bendamustine
Participants will receive intravenous (IV) infusion of bendamustine (90 or 70 milligrams per square meter [mg/m^2]) on Days 2-3 of Cycle 1 and Days 1-2 of Cycles 2-6.
Drug: Rituximab
Participants will receive IV infusion of rituximab (375 mg/m^2) on Day 1 of Cycle 1 and 500 mg/m^2 administered on Day 1 of Cycles 2-6.
Other Name: MabThera; Rituxan
Drug: Venetoclax
Participants will receive multiple doses of venetoclax orally once daily.
Other Name: ABT-199; GDC-0199

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of relapsing/refractory or previously untreated CLL
  • Eastern Cooperative Oncology Group (ECOG) performance score of less than equal to (</=) 1
  • Adequate bone marrow function
  • Adequate coagulation, renal and hepatic function
  • Hematological values within the limits independent of growth factor support or transfusion unless cytopenia is caused by the underlying disease, i.e., no evidence of additional bone marrow dysfunction (e.g., myelodysplastic syndrome, hypoplastic bone marrow)

Exclusion Criteria:

  • Participants received an allogeneic stem cell transplant
  • Known human immunodeficiency virus (HIV) positivity
  • Uncontrolled autoimmune hemolytic anemia or thrombocytopenia
  • Positive test results for chronic hepatitis B infection and hepatitis C virus (HCV)
  • Received any anti-cancer therapy including chemotherapy or radiotherapy, steroid therapy for anti-neoplastic intent, and investigational therapy, including targeted small molecule agents within 28 days prior to the first dose of study drug or has not recovered to less than Grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy
  • Significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01671904

Contacts
Contact: Reference Study ID Number: GO28440 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

Locations
United States, California
Active, not recruiting
La Jolla, California, United States, 92093
United States, Illinois
Active, not recruiting
Harvey, Illinois, United States, 60426
United States, Michigan
Active, not recruiting
Detroit, Michigan, United States, 48201
United States, Washington
Terminated
Spokane, Washington, United States, 99218
Terminated
Yakima, Washington, United States, 98902
Active, not recruiting
Yakima, Washington, United States, 98902
France
Recruiting
Lille, France, 59037
Recruiting
Montpellier, France, 34295
Recruiting
Pierre Benite, France, 69495
Recruiting
Rouen, France, 76038
Germany
Recruiting
Freiburg, Germany, 79106
Terminated
Kiel, Germany, 24105
Recruiting
Köln, Germany, 50924
Recruiting
München, Germany, 80804
Recruiting
Ulm, Germany, 89081
Sponsors and Collaborators
Genentech, Inc.
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Clinical Trials Genentech, Inc.
  More Information

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01671904     History of Changes
Other Study ID Numbers: GO28440  2012-002351-42 
Study First Received: August 10, 2012
Last Updated: November 1, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Obinutuzumab
Rituximab
Bendamustine Hydrochloride
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 09, 2016