This trial is active, not recruiting.

Condition chronic lymphocytic leukemia
Treatments bendamustine, gdc-0199, rituximab [mabthera/rituxan]
Phase phase 3
Target BCL-2
Sponsor Hoffmann-La Roche
Collaborator AbbVie
Start date March 2014
End date September 2018
Trial size 391 participants
Trial identifier NCT02005471, GO28667


This open-label, randomized study will compare the efficacy of GDC-0199 plus rituximab (GDC-0199+R) with bendamustine plus MabThera/Rituxan (Rituximab) (B+R) in patients with relapsed or resistant chronic lymphocytic leukemia. Patients will be randomized 1:1 into the two arms. Patients randomized to GDC-0199+R will be given GDC-0199 daily (oral, target dose 400 mg) and will receive 6 cycles of rituximab infused intravenously (IV) on Day 1 of each 28-day cycle (Cycle 1: 375 mg/m2; Cycles 2-6: 500 mg/m2).

Patients randomized to B+R will receive 6 cycles of treatment consisting of a rituximab infusion (Cycle 1: 375 mg/m2; Cycles 2-6: 500 mg/m2) on Day 1 and bendamustine infusions (70 mg/m2) on Days 1 and 2 of each 28-day cycle.

Patients in the GDC-0199+R arm will continue GDC-0199 treatment until disease progression or 2 years since treatment start, whichever comes first. Anticipated time on study is up to 5 years.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
(Active Comparator)
70 mg/m2 IV dose given on Days 1 and 2 of a 28-day cycle for 6 cycles.
rituximab [mabthera/rituxan]
Intravenous (IV) infusions given on Day 1 of a 28-day cycle for 6 cycles. First dose (Cycle 1): 375 mg/m2 Subsequent doses (Cycles 2-6): 500 mg/m2
4-5 week ramp-up until target daily dose of 400 mg is reached. The daily 400 mg dose will be taken orally for six 28-day cycles. Treatment will continue until disease progression or 2 years after treatment start, whichever comes first.
rituximab [mabthera/rituxan]
Intravenous (IV) infusions given on Day 1 of a 28-day cycle for 6 cycles. First dose (Cycle 1): 375 mg/m2 Subsequent doses (Cycles 2-6): 500 mg/m2

Primary Outcomes

Investigator-assessed progression-free survival (PFS), defined as time from randomization until disease progression or death from any cause.
time frame: Up to 5 years

Secondary Outcomes

Overall response rates
time frame: Assessed 2-3 months after end of treatment
Incidence of adverse events
time frame: Up to 5 years
Patient-reported outcome measure
time frame: Up to 5 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Age > / = 18 years. - Diagnosis of chronic lymphocytic leukemia (CLL) per diagnostic criteria and relapsed or refractory CLL per the iwCLL guidelines. - Previously treated with 1-3 lines of therapy (e.g. completed > / = two treatment cycles per therapy), including at least one standard chemotherapy-containing regimen. - Patients previously treated with bendamustine only if their duration of response was > / = 24 months. - Eastern Cooperative Oncology Group (ECOG) performance score of < / = 1. - Adequate bone marrow function. - Adequate renal and hepatic function. - Patients must use effective birth control throughout study until 1 year after rituximab treatment; female patients must not be pregnant or breast-feeding. Exclusion Criteria: - Transformation of CLL to aggressive non-Hodgkin lymphoma or CNS involvement by CLL. - Undergone an allogenic stem cell transplant. - A history of significant renal, neurologic, psychiatric, endocrine, metabolic, immunologic, cardiovascular or hepatic disease. - Hepatitis B or C or known HIV positive. - Receiving warfarin treatment. - Received an anti-CLL monoclonal antibody within 8 weeks prior to the first dose of study drug. - Received any anti-cancer or investigational therapy within 14 days prior to the first dose of study drug or has not recovered from previous therapy. - Received CYP3A4 inhibitors (such as fluconazole, ketoconazole and clarithromycin) or inducers (such as rifampin, carbamezapine, phenytoin, St. John's Wort) within 7 days prior to the first dose of GDC-0199. - Prior GDC-0199 treatment. - Patients with another cancer, history of another cancer considered uncured on in complete remission for < 5 years, or currently under treatment for another suspected cancer except non-melanoma skin cancer or carcinoma in situ of the cervix that has been treated or excised and is considered resolved. - Malabsorption syndrome or other condition that precludes enteral route of administration. - Other clinically significant uncontrolled condition(s) including, but not limited to, systemic infection (viral, bacterial or fungal). - Vaccination with a live vaccine within 28 days prior to randomization.

Additional Information

Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.