Phase 4 N=357 Randomized Treatment

A Study of MabThera Added to Bendamustine or Chlorambucil in Patients With Chronic Lymphocytic Leukemia (MaBLe)

Lymphocytic Leukemia, Chronic

Bottom Line

View on ClinicalTrials.gov: NCT01056510 ↗

Enrolled (actual)

357

Serious AEs

36.3%

Results posted

Jun 2015

Primary outcome: Primary: Percentage of Participants Achieving Confirmed Complete Response (CR) According to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 Guidelines in the First-Line Subpopulation After 6 Cycles of Therapy — 24; 9.2; 2.5; 5.8 percentage of participants — p=0.002

Study Design & Population

Study type: Interventional
Phase: Phase 4
Interventions: bendamustine (Drug); chlorambucil (Drug); rituximab [MabThera/Rituxan] (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Hoffmann-La Roche
Primary completion: Mar 2014

Outcome Measures

Outcome	Result	p-value
PRIMARY Percentage of Participants Achieving Confirmed Complete Response (CR) According to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 Guidelines in the First-Line Subpopulation After 6 Cycles of Therapy	24; 9.2; 2.5; 5.8; 73.6; 85	0.002 sig
SECONDARY Percentage of Participants Achieving Confirmed CR According to IWCLL 2008 Guidelines in the Pooled Population After 6 Cycles of Therapy	21.3; 6.7; 2.8; 4.5; 75.8; 88.8	< 0.001 sig
SECONDARY Percentage of Participants Achieving Confirmed CR According to IWCLL 2008 Guidelines in the Second-Line Subpopulation After 6 Cycles of Therapy	15.8; 1.7; 3.5; 1.7; 80.7; 96.6	0.009 sig
SECONDARY Percentage of Participants Achieving a Best Overall Response of CR, CR With Incomplete Marrow Recovery (CRi), Partial Response (PR), or Nodular PR (nPR) in the First-Line Subpopulation	78.5; 80.0; 75.2; 79.2; 90.9; 85.8	0.900
SECONDARY Percentage of Participants by Disease Response Category in the First-Line Subpopulation	21.5; 9.2; 2.5; 0; 1.7; 6.7	—
SECONDARY Percentage of Participants Experiencing PD or Death in the First-Line Subpopulation	27.3; 46.7	—
SECONDARY Progression-Free Survival (PFS) in the First-Line Subpopulation	39.6; 29.9	0.003 sig
SECONDARY Percentage of Participants With Tumor Response of CR or CRi Experiencing PD or Death in the First-Line Subpopulation	17.8; 33.8	—
SECONDARY Disease-Free Survival (DFS) in the First-Line Subpopulation	36.8; 32.0	0.029 sig
SECONDARY Percentage of Participants Experiencing PD, Documented Intake of New Leukemia Therapy, or Death in the First-Line Subpopulation	29.8; 49.2	—
SECONDARY Event-Free Survival (EFS) in the First-Line Subpopulation	39.6; 29.9	0.006 sig
SECONDARY Percentage of Participants With Documented Intake of New Leukemia Therapy in the First-Line Subpopulation	9.1; 18.3	—
SECONDARY Time to Next Leukemia Treatment (TNLT) in the First-Line Subpopulation	NA; NA	0.037 sig
SECONDARY Percentage of Participants With Tumor Response of CR, CRi, PR, or nPR Experiencing PD or Death in the First-Line Subpopulation	24.6; 43.9	—
SECONDARY Duration of Response in the First-Line Subpopulation	36.8; 27.7	0.007 sig
SECONDARY Percentage of Participants Experiencing Death in the First-Line Subpopulation	14.9; 15.0	—
SECONDARY Overall Survival (OS) in the First-Line Subpopulation	43.8; NA	0.986
SECONDARY Percentage of Participants Achieving Molecular Response in the First-Line Subpopulation	57.1; 16.0; 42.9; 84.0	< 0.001 sig
SECONDARY Number of Participants With Positive and Negative Outcome for MRD in the First-Line Subpopulation	30; 64; 48; 14	—
SECONDARY Proportion of Malignant B-cells in Normal B-cells Among Participants With a Positive Outcome for MRD in the First-Line Subpopulation	0.0836; 0.1125	—

Summary

This randomized, open-label, parallel group study will assess the effect on response rate and the safety of MabThera added to either bendamustine or chlorambucil in patients with chronic lymphocytic leukemia. Patients will be randomized to receive six 4-week cycles of either A) MabThera (375mg/m2 iv day 1 of cycle 1, 500mg/m2 iv cycles 2-6) plus bendamustine (90mg/m2 as first-line or 70mg/m2 as second-line therapy, iv on days 1 and 2, cycles 1-6), or B)MabThera plus chlorambucil (10mg/m2 po daily, days 1-7, cycles 1-6). Patients in group B can receive up to 6 further cycles of chlorambucil as monotherapy. Anticipated time on study treatment is 6-12 months, and target sample size is 600-700 individuals.

Eligibility Criteria

Inclusion Criteria

adult patients, >/=18 years of age
chronic lymphocytic leukemia
active CLL with progressive Binet stage B or C
ineligible for treatment with fludarabine
for second line patients, only pretreatment with rituximab and/or chlorambucil is allowed
EOCG performance status >/=2

Exclusion Criteria

patients who have relapsed within /=20mg daily prednisolone or equivalent

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01056510). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.