Clinical trial NCT00532129: A Study of MabThera (Rituximab) Plus Chlorambucil in Participants With Chronic Lymphocytic Leukemia.
Official title: An Open-Label Study to Characterize the Safety and Response Rate of MabThera (Rituximab) Plus Chlorambucil in Previously Untreated Patients With CD20-Positive B-Cell Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphocytic Leukemia, Chronic
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2007-09-19
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This single arm study will assess the safety and effect on response rate of a combination of rituximab and chlorambucil in previously untreated participants with B-cell chronic lymphocytic leukemia. Participants will receive 6 monthly cycles of combination treatment, followed by up to 6 cycles of chlorambucil alone. Rituximab will be administered on Day 1 of each cycle, at a dose of 375 milligrams per square meter (mg/m\^2) intravenously (IV) in Cycle 1, and 500 mg/m\^2 in subsequent cycles, and chlorambucil will be administered on Days 1-7 of each cycle at a dose of 10 mg/m\^2/day per oral (PO).


Eligibility criteria: Inclusion Criteria:

* previously untreated participants with cluster of differentiation 20 (CD20) positive B-cell chronic lymphocytic leukemia;
* participants with progressive Binet stage B, or C requiring therapy according to National Cancer Institute (NCI) criteria;
* Eastern Cooperative Oncology Group (ECOG) performance status \<=2.

Exclusion Criteria:

* previous treatment for Chronic Lymphocytic Leukaemia (CLL);
* known concomitant hematological malignancy;
* transformation to aggressive B-cell malignancy;
* history of severe cardiac disease;
* known hypersensitivity or anaphylactic reactions to murine antibodies.

Primary outcomes:
measure: Percentage of Participants With Treatment-Emergent Adverse Events (AEs)
timeFrame: First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
Secondary outcomes:
measure: Percentage of Participants With Best Overall Response (BOR) of Clinical CR or Confirmed CR
timeFrame: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)
measure: Percentage of Participants With BOR of Partial Response (PR)
timeFrame: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)
measure: Percentage of Participants With BOR of Nodular Partial Response (nPR)
timeFrame: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)
measure: Percentage of Participants With BOR of Progressive Disease (PD)
timeFrame: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)
measure: Percentage of Participants With BOR of Stable Disease (SD)
timeFrame: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)
measure: Percentage of Participants With Objective Response (CR or PR)
timeFrame: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)
measure: Percentage of Participant With Disease Progression or Death
timeFrame: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)
measure: Progression Free Survival (PFS) Time
timeFrame: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)
measure: Disease Free Survival (DFS) Time
timeFrame: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)
measure: Duration of Response (DoR)
timeFrame: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)
measure: Percentage of Participants Who Died
timeFrame: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)
measure: Overall Survival (OS) Time
timeFrame: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)
measure: Percentage of Participants Who Achieved Minimal Residual Disease (MRD) Negativity
timeFrame: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)
measure: Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
timeFrame: Baseline, Day 1 of Cycles 5 and 11, end of follow-up (FU) (24 month [m] FU visit, up to approximately 3 years)
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
city: Bournemouth
country: United Kingdom
city: Cambridge
country: United Kingdom
city: Canterbury
country: United Kingdom
city: Cottingham
country: United Kingdom
city: Leeds
country: United Kingdom
city: Leicester
country: United Kingdom
city: Liverpool
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: Sutton
country: United Kingdom
city: Wakefield
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Hillmen P, Gribben JG, Follows GA, Milligan D, Sayala HA, Moreton P, Oscier DG, Dearden CE, Kennedy DB, Pettitt AR, Nathwani A, Varghese A, Cohen D, Rawstron A, Oertel S, Pocock CF. Rituximab plus chlorambucil as first-line treatment for chronic lymphocytic leukemia: Final analysis of an open-label phase II study. J Clin Oncol. 2014 Apr 20;32(12):1236-41. doi: 10.1200/JCO.2013.49.6547. Epub 2014 Mar 17.