A Study to Compare the Efficacy and Safety of Obinutuzumab + GDC-0199 versus Obinutuzumab + Chlorambucil in Patients with Chronic Lymphocytic Leukemia

Phase 1

Conditions: chronic lymphocytic leukemia
MedDRA version: 20.1Level: LLTClassification code 10008976Term: Chronic lymphocytic leukemiaSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2014-001810-24-FR

Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 445

Inclusion Criteria

- Documented previously untreated CLL according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria
- CLL requiring treatment according to IWCLL criteria
- Total Cumulative Illness Rating Scale (CIRS score) > 6 or CrCl < 70 mL/min
- Adequate marrow function independent of growth factor or transfusion support within 2 weeks of screening as per protocol, unless cytopenia is due to marrow involvement of CLL
- Adequate liver function
- Life expectancy > 6 months
- Agreement to use highly effective contraceptive methods per protocol
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 75
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 357

Exclusion Criteria

- Transformation of CLL to aggressive Non-Hodgkin's lymphoma (Richters transformation or pro-lymphocytic leukemia)
- Known central nervous system involvement
- Patients with a history of confirmed progressive multifocal leukoencephalopathy (PML)
- An individual organ/ system impairment score of 4 as assessed by the CIRS definition limiting the ability to receive the treatment regimen of this trial with the exception of eyes, ears, nose, throat organ system
- Patients with uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
- Inadequate renal function
- History of prior malignancy, except for conditions as listed in the protocol if patients have recovered from the acute side effects incurred as a result of previous therapy
- Patients with active bacterial, viral, or fungal infection requiring systemic treatment within the last two months prior to registration
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
- Hypersensitivity to chlorambucil, obinutuzumab, or GDC-0199 or to any of the excipients
- Pregnant women and nursing mothers
- Positive test results for chronic HBV infection (defined as positive HBsAg serology) or positive test result for hepatitis C (hepatitis C virus [HCV] antibody serology testing)
- Patients with known infection with human immunodeficiency virus (HIV) or human T-cell leukemia virus-1 (HTLV-1)
- Requires the use of warfarin, marcumar, or phenprocoumon
- Received agents known to be strong CYP3A4 inhibitors or inducers within 7 days prior to the first dose of study drug

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine efficacy by investigator-assessed PFS of a combined regimen of obinutuzumab and GDC 0199 compared with GClb in previously untreated patients with CLL who have coexisting medical conditions.;Secondary Objective: To determine efficacy as assessed by additional outcome measures, including Independent Review Committee [IRC]-assessed PFS, overall response and MRD response rate as measured by allele-specific oligonucleotide polymerase chain reaction [ASO-PCR] <br>;Primary end point(s): Progression-free survival (PFS), defined as the time from randomization to the first occurrence of progression, relapse or death from any cause as assessed by the investigator using IWCLL criteria;Timepoint(s) of evaluation of this end point: At baseline, day 1 of cycle 7 and 9, day 1 of cycle 4, day 28 after treatment completion or early termination, during follow up i.e. 3 months after treatment completion or early termination and then regularly until 5 years from last patient enrolled.<br>

Secondary Outcome Measures

Name	Time	Method

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