CLL11: A Study of Rituximab With Chlorambucil or Chlorambucil Alone in Patients With Previously Untreated Chronic Lymphocytic Leukemia (Stage 1b)

Roche

Status and phase: Completed; Phase 3

Conditions: Lymphocytic Leukemia, Chronic

Treatments: Drug: rituximab; Drug: obinutuzumab; Drug: chlorambucil

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01998880

2009-012476-28 CLL1;

BO21004 (Stage 1b)

Details and patient eligibility

About

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 (1000mg 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.

Full 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 here.
• BO21004 (Stage 2) [NCT02053610] includes the analysis of 2 of the 3 arms obinutuzumab plus chlorambucil (Glb) compared to rituximab plus chlorambucil (RClb) reported separately.

Enrollment: 787 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 lymphectomy alone
• Positive hepatitis serology (HBV, HCV) or positive HIV or Human T Cell Leukemia Virus (HTLV) testing
• Patients with active infection requiring systemic treatment

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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787 participants in 3 patient groups

obinutuzumab + chlorambucil (GClb)

Experimental group

Description:

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).

Treatment:

Drug: chlorambucil

Drug: obinutuzumab

rituximab + chlorambucil (RClb)

Active Comparator group

Description:

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).

Treatment:

Drug: chlorambucil

Drug: rituximab

Chlorambucil (Clb)

Active Comparator group

Description:

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.

Treatment:

Drug: chlorambucil