An Expanded Access, Open-Label Study of Obinutuzumab (GA101) Plus Chlorambucil in Patients With Previously Untreated Chronic Lymphocytic Leukemia

Study Overview
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Brief Summary
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This is a multicenter, open-label, single-arm, expanded access treatment study designed to provide obinutuzumab to patients with previously untreated Chronic Lymphocytic Leukemia (CLL) in combination with chlorambucil and to evaluate the safety and efficacy of obinutuzumab administered in combination with chlorambucil. This study will enroll patients with previously untreated CD20-positive CLL requiring treatment according to the IWCLL guidelines (Hallek et al 2008), as assessed by the investigator.

Official Title
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An Expanded Access, Open-Label Study of Obinutuzumab (GA101) Plus Chlorambucil in Patients With Previously Untreated Chronic Lymphocytic Leukemia

Conditions
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Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: Obinutuzumab
* Drug: Chlorambucil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of CD20-positive CLL (per IWCLL guidelines, Hallek et al 2008) Previously untreated CLL requiring treatment according to the IWCLL guidelines (Hallek et al 2008), as assessed by the investigator Adequate baseline bone marrow function unless it due to underlying CLL disease No previous treatment for CLL by chemotherapy, radiotherapy, or immunotherapy Patients who are not appropriate to receive more intensive chemotherapy in the judgment of the investigator Life expectancy of > 6 months Exclusion Criteria: Treatment with any other investigational agent or participation in another clinical trial within 28 days prior to the start of Cycle 1 Transformation of CLL to aggressive B-cell malignancy History of severe allergic or anaphylactic reactions to monoclonal antibody therapy Known hypersensitivity to chlorambucil or any of its excipients History of other malignancy that could affect compliance with the protocol or interpretation of results Known active bacterial, viral, fungal, mycobacterial, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with IV antibiotics or hospitalization (related to the completion of the course of antibiotics) within 4 weeks before the start of Cycle 1 Major surgery (within 4 weeks prior to the start of Cycle 1), other than for diagnosis Known infection with human immunodeficiency virus (HIV) or Human T-Cell Leukemia Virus 1 (HTLV-1) seropositive status Positive hepatitis serology Women who are pregnant or lactating Fertile men or women of childbearing potential unless 1) surgically sterile or 2) using an adequate measure of contraception such as oral contraceptives, intrauterine device, or barrier method of contraception in conjunction with spermicidal jelly Effective contraception is required while receiving obinutuzumab. For women, effective contraception is required to continue for >= 12 months after the last dose of obinutuzumab. For men, effective contraception is required to continue for 6 months after the last dose of chlorambucil treatment. Vaccination with a live vaccine a minimum of 28 days prior to the start of Cycle 1

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Obinutuzumab + Chlorambucil<br>Obinutuzumab was administered intravenously for 6 cycles (28-day cycles) as: 100 mg on Day 1, 900 mg on Day 2, and 1000 mg on Days 8 and 15 for Cycle 1; and 1000 mg on Day 1 of Cycles 2 to 6. Chlorambucil was administered orally at a dose of 0.5 mg/kg body weight on Days 1 and 15 for Cycles 1 through 6 (28-day cycles). | Drug: Obinutuzumab<br> <br> * Other names: RO 5072759, GA101;Drug: Chlorambucil<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Received Obinutuzumab and Chlorambucil in the Study | Number of participants who received obinutuzumab and chlorambucil in the study are presented in the below table. | Cycles 1 to 6 (28-day cycles) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs), AEs of Grade 3 and Above Severity, AEs of Special Interest (AESI), AEs Leading to Obinutuzumab Discontinuation or Dose Delays, Serious Adverse Events (SAEs), and Death | An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0 was used for grading the AEs. According to NCI CTCAE, Grade 3 = severe or medically significant but not immediately life threatening; Grade 4 = life-threatening consequences, urgent intervention indicated, and Grade 5 = death. AESIs included all tumor lysis syndrome, serious infections, serious infusion-related reactions (IRR), and hepatitis B reactivation. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect. | Up to 28 days after the last dose of study drug (up to 7 months from Day 1) | 
| Number of Participants With Objective Response | Objective response is defined as either complete response [CR], complete response with incomplete recovery [CRi], or partial response [PR] as determined by the treating physician's standard practice at the end of treatment or premature discontinuation from study per the International Workshop on Chronic Lymphocytic Leukemia Criteria (iwCLL criteria). Patients who have not achieved a CR or a PR, and who have not exhibited progressive disease, will be considered to have stable disease (which is equivalent to a nonresponse). | Up to end of treatment or premature discontinuation from study (up to 7 months from Day 1) |