Clinical trial NCT01671904: A Study of Venetoclax in Combination With Bendamustine + Rituximab or Bendamustine + Obinutuzumab in Participants With Relapsed/Refractory or Previously Untreated Chronic Lymphocytic Leukemia (CLL)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Lymphocytic Leukemia
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
Collaborators: name: AbbVie (prior sponsor, Abbott)
First posted: 2012-08-24
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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 first-line (1L)/previously untreated or relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). The study will explore two venetoclax combination regimens in participants with 1L CLL: BR+venetolax (V) and BG+V. Participants with R/R CLL will be administered BR+V.


Eligibility 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

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Schedule (Sch) A (venetoclax [V] introduced before other agents): Cycle 1 Day 1 (Cy1D1) to Cy1D21; Sch B (V introduced after other agents): Cy1D21 to Cy2D28; Cycle length = 28 days.
Secondary outcomes:
measure: Plasma Concentrations of Venetoclax
timeFrame: Sch A: Ramp-up D1, 8, 15, 22, 29: predose (pd), 8 h; Cy1D1: pd; Cy1D3: pd, 2, 4, 6, 8, 10 h; Cy2D1, Cy4D1, Cy6D1: pd. Sch B: Cy1D1: pd; Cy1D22, Cy2D1, Cy2D8, Cy2D15, Cy2D22 (ramp-up): pd, 8 h; Cy3D1: pd, 2, 4, 6, 8 h; Cy4D1, Cy6D1: pd.
measure: Serum Concentrations of Rituximab
timeFrame: Sch A: Cy1D1, Cy2D1, Cy4D1, Cy6D1: predose, end of infusion. Sch B: Cy1D1: predose, end of infusion; Cy2D1, (ramp-up): predose, end of infusion; Cy3D1, Cy4D1, Cy6D1: predose.
measure: Serum Concentrations of Obinutuzumab
timeFrame: Sch A: Cy1D1, Cy1D2: pd, end of infusion (EoI); Cy1D3: pd; Cy1D8, Cy1D15, Cy2D1: pd, EoI; Cy3D1, Cy4D1, Cy5D1, Cy6D1: pd; Sch B: Cy1D1, Cy1D2, Cy1D8, Cy1D15: pd, EoI; Cy1D22 (ramp-up): pd; Cy2D1, Cy3D1, Cy4D1, Cy5D1, Cy6D1: pd, EoI.
measure: Plasma Concentrations of Bendamustine
timeFrame: Sch A: Cy1D2: predose, end of infusion. Sch B: Cy1D2, Cy3D2: predose, end of infusion.
measure: 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
timeFrame: Baseline up to approximately 5.75 years
measure: Duration of Response According to IWCLL 2008 Guidelines
timeFrame: Baseline up to approximately 5.75 years
measure: Percentage of Participants with CR
timeFrame: Baseline up to approximately 5.75 years
measure: Progression-Free Survival (PFS) According to IWCLL 2008 Guidelines
timeFrame: Baseline up to approximately 5.75 years
measure: Overall Survival (OS)
timeFrame: Baseline up to approximately 5.75 years
measure: Number of Participants With Adverse Events
timeFrame: Up to approximately 5.75 years
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego Medical Center
state: California
city: Harvey
country: United States
facility: Ingalls Hospital; Cancer Clinical Trials
state: Illinois
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Yakima
country: United States
facility: North Star Lodge
state: Washington
city: Lille
country: France
facility: Hopital Claude Huriez
city: Montpellier
country: France
facility: Hopital Saint Eloi
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Freiburg
country: Germany
facility: Apotheke des Universitätsklinikums Freiburg
city: Köln
country: Germany
facility: Universitatsklinik Koln
city: München
country: Germany
facility: Klinikum Schwabing
city: Ulm
country: Germany
facility: Universtitätsklinikum Ulm; Klinik für Innere Medizin III
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References: