Overview

This trial is active, not recruiting.

Condition lymphocytic leukemia, chronic
Treatments obinutuzumab, rituximab, chlorambucil
Phase phase 3
Target CD20
Sponsor Hoffmann-La Roche
Collaborator German CLL Study Group
Start date December 2009
End date August 2013
Trial size 787 participants
Trial identifier NCT02053610, 2009-012476-28; CLL1, BO21004 (Stage 2)

Summary

This open-label, randomized, 3-arm study will evaluate the efficacy and safety of (obinutuzumab) RO5072759 in combination with chlorambucil as compared to rituximab plus chlorambucil or chlorambucil alone in patients with previously untreated chronic lymphocytic leukemia (CLL). Patients will be randomized 2:2:1 to receive a maximum of six 28-day cycles of either RO5072759 (1000 mg intravenous (iv) infusion, on days 1, 8 and 15 of cycle 1 and day 1 of cycles 2-6) plus chlorambucil (0.5 mg/kg orally, days 1 and 15 of cycles 1-6), or rituximab (iv infusion day 1, 375 mg/m^2 cycle 1, 500 mg/m^2 cycles 2-6) plus chlorambucil, or chlorambucil alone. Anticipated time on study treatment is >6 months and follow-up for disease-progression and safety will be at least 5 years. In the US, this trial is sponsored/managed by Genentech.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Participants received 1000 mg obinutuzumab intravenous (IV) infusion, on Days 1 [first infusion split 100 mg on Day 1 and 900 mg on Day 2 as per protocol amendment], 8 and 15 in Cycle 1 and Day 1 in Cycles 2-6 (28-day cycles) plus chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles).
obinutuzumab RO5072759
1000 mg obinutuzumab intravenous (IV) infusion, on Days 1 [first infusion split 100 mg on Day 1 and 900 mg on Day 2 as per protocol amendment], 8 and 15 in Cycle 1 and Day 1 in Cycles 2-6 (28-day cycles).
chlorambucil
Chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle
(Active Comparator)
Participants received 375 mg/m^2 rituximab IV infusion on Day 1 of Cycle 1 then 500 mg/m^2 IV infusions on Day 1 of Cycles 2-6 (28-day cycles) plus chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 cycles).
rituximab Rituxan®
375 mg/m^2 rituximab intravenous (IV) infusion on Day 1 of Cycle 1 (Cycle duration is 28 days) then 500 mg/m^2 IV infusions on Day 1 of Cycles 2-6.
chlorambucil
Chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle
(Active Comparator)
Participants received chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles). Participants with Progressive Disease or within 6 months of follow-up were allowed to cross over to receive obinutuzumab + chlorambucil.
chlorambucil
Chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle

Primary Outcomes

Measure
Progression-free Survival (PFS)
time frame: Randomization to clinical cutoff (median observation 18.8 months GClb and 18.6 months RClb)
Percentage of Participants With Progression Free Survival Events
time frame: Randomization to clinical cutoff (median observation 18.8 months GClb and 18.6 months RClb)

Secondary Outcomes

Measure
Progression Free Survival Based on Independent Review Committee (IRC) Data
time frame: Randomization to clinical cutoff (median observation 18.8 months GClb and 18.6 months RClb)
Percentage of Participants With Progression Free Survival Events Based on Independent Review Committee (IRC) Data
time frame: Randomization to clinical cutoff (median observation 18.8 months GClb and 18.6 months RClb)
Percentage of Participants With End of Treatment Response (EOTR)
time frame: Randomization to clinical cutoff (median observation 18.8 months GClb and 18.6 months RClb)
Percentage of Participants With Best Overall Response [Time Frame: Randomization to Clinical Cutoff (Median Observation 14.2 Months)]
time frame: Randomization to clinical cutoff (median observation 18.8 months GClb and 18.6 months RClb)
Event Free Survival
time frame: Randomization to clinical cutoff (median observation 18.8 months GClb and 18.6 months RClb)
Overall Survival
time frame: Randomization to clinical cutoff (median observation 18.8 months GClb and 18.6 months RClb)
Duration of Response
time frame: Randomization to clinical cutoff (median observation 18.8 months GClb and 18.6 months RClb)
Percentage of Participants With Molecular Remission at the End of Treatment
time frame: Randomization to clinical cutoff (median observation 18.8 months GClb and 18.6 months RClb)
Time to Re-Treatment/New-antileukemic Therapy
time frame: Randomization to clinical cutoff (median observation 18.8 months GClb and 18.6 months RClb)
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire Score
time frame: after 3 cycles, 28 days after last dose and at intervals during follow-up
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) QLQ-CLL16 Questionnaire Score
time frame: after 3 cycles, 28 days after last dose and at intervals during follow-up

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Adults >/=18 years - Documented Cluster of Differentiation Antigen 20 (CD20) + B-Cell Chronic Lymphocytic Lymphoma (B-CLL) - Previously untreated Chronic Lymphocytic Leukemia (CLL) requiring treatment according to the National Cancer Institute (NCI) criteria - Total Cumulative Illness Rating Scale (CIRS) > 6 and/or creatinine clearance < 70 ml/min. Exclusion Criteria: - Prior CLL therapy - Transformation of CLL to aggressive Non-Hodgkin's Lymphoma (NHL) (Richter's transformation) - History of other malignancy unless the malignancy has been in remission without treatment for >/=2 years prior to enrolment, and except for carcinoma in situ of the cervix, basal or squamous cell skin cancer, surgically treated low-grade prostate cancer, or ductal carcinoma in situ (DCIS) of the breast treated with lumpectomy alone - Positive hepatitis serology (HBV, HCV) or positive HIV or Human T-Cell Leukemia Virus (HTLV) testing - Patients with active infection requiring systemic treatment.

Additional Information

Official title An Open-label, Multi-center, Three Arm Randomized Study to Investigate the Safety and Efficacy on Progression-free Survival of RO5072759 + Chlorambucil (GClb) Compared to Rituximab + Chlorambucil (RClb) or Chlorambucil (Clb) Alone in Previously Untreated CLL Patients With Comorbidities.
Description Protocol BO21004 is divided into 3 separate Unique Protocol IDs for reporting results on clinicaltrials.gov because there are 3 separate primary analyses conducted at different time-points. - BO21004 (Stage 1a) [NCT01010061] includes the analysis of 2 of the 3 arms obinutuzumab plus chlorambucil (Glb) compared to chlorambucil (Clb) reported separately. - BO21004 (Stage 1b) [NCT01998880] includes the analysis of 2 of the 3 arms rituximab plus chlorambucil (RClb) compared to chlorambucil (Clb) reported separately. - BO21004 (Stage 2) includes the analysis of 2 of the 3 arms obinutuzumab plus chlorambucil (Glb) compared to rituximab plus chlorambucil (RClb) reported here.
Trial information was received from ClinicalTrials.gov and was last updated in October 2014.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.