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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

August 10, 2012
November 1, 2016
January 2014
November 2016   (final data collection date for primary outcome measure)
  • 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 ]
  • Maximum Tolerated Dose [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Safety: incidence of adverse events [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01671904 on ClinicalTrials.gov Archive Site
  • 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 ]
Pharmacokinetics: Area Under the Concentration Time Curve [ Time Frame: Pre-dose and up to 24 h post-dose of each dosing day ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Study of Venetoclax in Combination With Bendamustine + Rituximab or Bendamustine + Obinutuzumab in Participants With Relapsed/Refractory or Previously Untreated Chronic Lymphocytic Leukemia (CLL)
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
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.
Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Chronic Lymphocytic Leukemia
  • 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: 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 (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.
    Interventions:
    • Drug: Bendamustine
    • Drug: Obinutuzumab
    • Drug: Venetoclax
  • 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.
    Interventions:
    • Drug: Bendamustine
    • Drug: Rituximab
    • Drug: Venetoclax
  • 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.
    Interventions:
    • Drug: Bendamustine
    • Drug: Rituximab
    • Drug: Venetoclax
  • 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.
    Interventions:
    • Drug: Bendamustine
    • Drug: Obinutuzumab
    • Drug: Venetoclax
  • 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.
    Interventions:
    • Drug: Bendamustine
    • Drug: Rituximab
    • Drug: Venetoclax
  • 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.
    Interventions:
    • Drug: Bendamustine
    • Drug: Rituximab
    • Drug: Venetoclax
  • 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.
    Interventions:
    • Drug: Bendamustine
    • Drug: Obinutuzumab
    • Drug: Venetoclax
  • 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.
    Interventions:
    • Drug: Bendamustine
    • Drug: Rituximab
    • Drug: Venetoclax
  • 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.
    Interventions:
    • Drug: Bendamustine
    • Drug: Rituximab
    • Drug: Venetoclax
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
100
May 2020
November 2016   (final data collection date for primary outcome measure)

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
Both
18 Years and older   (Adult, Senior)
No
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
United States,   France,   Germany
 
NCT01671904
GO28440, 2012-002351-42
Not Provided
Not Provided
Not Provided
Genentech, Inc.
Genentech, Inc.
AbbVie (prior sponsor, Abbott)
Study Director: Clinical Trials Genentech, Inc.
Genentech, Inc.
November 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP