Clinical trial NCT01056510: A Study of MabThera Added to Bendamustine or Chlorambucil in Patients With Chronic Lymphocytic Leukemia (MaBLe)
Official title: A Randomized Study to Assess the Effect on Response Rate of MabThera (Rituximab) Added to a Standard Chemotherapy, Bendamustine or Chlorambucil, in Patients With Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Lymphocytic Leukemia, Chronic
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2010-01-26
Enrollment: 357
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 \<12 months of first dose of prior rituximab or chlorambucil first-line therapy
* previous or planned stem cell transplantation
* radioimmunotherapy within 6 months prior to starting study treatment
* transformation to aggressive B-cell malignancy
* any other concurrent anti-cancer therapy, or glucocorticoid \>/=20mg daily prednisolone or equivalent

Primary outcomes:
measure: 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
timeFrame: At least 2 months after completion of therapy (up to 32 weeks)
Secondary outcomes:
measure: Percentage of Participants Achieving Confirmed CR According to IWCLL 2008 Guidelines in the Pooled Population After 6 Cycles of Therapy
timeFrame: At least 2 months after completion of therapy (up to 32 weeks)
measure: Percentage of Participants Achieving Confirmed CR According to IWCLL 2008 Guidelines in the Second-Line Subpopulation After 6 Cycles of Therapy
timeFrame: At least 2 months after completion of therapy (up to 32 weeks)
measure: 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
timeFrame: After 3 and 6 treatment cycles and from Baseline to the end-of-treatment (EOT) visit, completed within 10 days before cutoff for data collection
measure: Percentage of Participants by Disease Response Category in the First-Line Subpopulation
timeFrame: After 6 treatment cycles and at the confirmation of response assessment at least 12 weeks later (up to 36 weeks)
measure: Percentage of Participants Experiencing PD or Death in the First-Line Subpopulation
timeFrame: End of Cycles 3 and 6 (both treatment arms), end of Cycles 7 to 12 (Rituximab + Chlorambucil arm), after an additional 8 weeks as confirmation of response, then every 3 months for 1 year, then every 6 months until study cutoff (up to 4.5 years)
measure: Progression-Free Survival (PFS) in the First-Line Subpopulation
timeFrame: End of Cycles 3 and 6 (both treatment arms), end of Cycles 7 to 12 (Rituximab + Chlorambucil arm), after an additional 8 weeks as confirmation of response, then every 3 months for 1 year, then every 6 months until study cutoff (up to 4.5 years)
measure: Percentage of Participants With Tumor Response of CR or CRi Experiencing PD or Death in the First-Line Subpopulation
timeFrame: End of Cycles 3 and 6 (both treatment arms), end of Cycles 7 to 12 (Rituximab + Chlorambucil arm), after an additional 8 weeks as confirmation of response, then every 3 months for 1 year, then every 6 months until study cutoff (up to 4.5 years)
measure: Disease-Free Survival (DFS) in the First-Line Subpopulation
timeFrame: End of Cycles 3 and 6 (both treatment arms), end of Cycles 7 to 12 (Rituximab + Chlorambucil arm), after an additional 8 weeks as confirmation of response, then every 3 months for 1 year, then every 6 months until study cutoff (up to 4.5 years)
measure: Percentage of Participants Experiencing PD, Documented Intake of New Leukemia Therapy, or Death in the First-Line Subpopulation
timeFrame: End of Cycles 3 and 6 (both treatment arms), end of Cycles 7 to 12 (Rituximab + Chlorambucil arm), after an additional 8 weeks as confirmation of response, then every 3 months for 1 year, then every 6 months until study cutoff (up to 4.5 years)
measure: Event-Free Survival (EFS) in the First-Line Subpopulation
timeFrame: End of Cycles 3 and 6 (both treatment arms), end of Cycles 7 to 12 (Rituximab + Chlorambucil arm), after an additional 8 weeks as confirmation of response, then every 3 months for 1 year, then every 6 months until study cutoff (up to 4.5 years)
measure: Percentage of Participants With Documented Intake of New Leukemia Therapy in the First-Line Subpopulation
timeFrame: During Cycles 1 to 6 (both treatment arms), Cycles 7 to 12 (Rituximab + Chlorambucil arm), after an additional 8 weeks, then every 3 months for 1 year, then every 6 months until study cutoff (up to 4.5 years)
measure: Time to Next Leukemia Treatment (TNLT) in the First-Line Subpopulation
timeFrame: During Cycles 1 to 6 (both treatment arms), Cycles 7 to 12 (Rituximab + Chlorambucil arm), after an additional 8 weeks, then every 3 months for 1 year, then every 6 months until study cutoff (up to 4.5 years)
measure: Percentage of Participants With Tumor Response of CR, CRi, PR, or nPR Experiencing PD or Death in the First-Line Subpopulation
timeFrame: End of Cycles 3 and 6 (both treatment arms), end of Cycles 7 to 12 (Rituximab + Chlorambucil arm), after an additional 8 weeks as confirmation of response, then every 3 months for 1 year, then every 6 months until study cutoff (up to 4.5 years)
measure: Duration of Response in the First-Line Subpopulation
timeFrame: End of Cycles 3 and 6 (both treatment arms), end of Cycles 7 to 12 (Rituximab + Chlorambucil arm), after an additional 8 weeks as confirmation of response, then every 3 months for 1 year, then every 6 months until study cutoff (up to 4.5 years)
measure: Percentage of Participants Experiencing Death in the First-Line Subpopulation
timeFrame: End of Cycles 3 and 6 (both treatment arms), end of Cycles 7 to 12 (Rituximab + Chlorambucil arm), after an additional 8 weeks as confirmation of response, then every 3 months for 1 year, then every 6 months until study cutoff (up to 4.5 years)
measure: Overall Survival (OS) in the First-Line Subpopulation
timeFrame: End of Cycles 3 and 6 (both treatment arms), end of Cycles 7 to 12 (Rituximab + Chlorambucil arm), after an additional 8 weeks as confirmation of response, then every 3 months for 1 year, then every 6 months until study cutoff (up to 4.5 years)
measure: Percentage of Participants Achieving Molecular Response in the First-Line Subpopulation
timeFrame: Up to 4 months after the last treatment cycle (up to 40 weeks)
measure: Number of Participants With Positive and Negative Outcome for MRD in the First-Line Subpopulation
timeFrame: After 6 treatment cycles (up to 24 weeks)
measure: Proportion of Malignant B-cells in Normal B-cells Among Participants With a Positive Outcome for MRD in the First-Line Subpopulation
timeFrame: After 6 treatment cycles (up to 24 weeks)
Other outcomes:
Locations:
city: Pori
country: Finland
city: Vantaa
country: Finland
city: Argenteuil
country: France
city: Avignon
country: France
city: Blois
country: France
city: Bordeaux
country: France
city: Brest
country: France
city: La Roche Sur Yon
country: France
city: La Tronche
country: France
city: Le Mans
country: France
city: Lens
country: France
city: Limoges
country: France
city: Lyon
country: France
city: Marseille
country: France
city: Mulhouse
country: France
city: Nice
country: France
city: Nimes
country: France
city: Paris
country: France
city: Paris
country: France
city: Perpignan
country: France
city: Pierre Benite
country: France
city: Salouel
country: France
city: Coimbra
country: Portugal
city: Lisboa
country: Portugal
city: Lisboa
country: Portugal
city: Porto
country: Portugal
city: Porto
country: Portugal
city: Vitoria
country: Spain
state: Alava
city: Elche
country: Spain
state: Alicante
city: Jerez de La Frontera
country: Spain
state: Cadiz
city: Torrelavega
country: Spain
state: Cantabria
city: La Coruna
country: Spain
state: La Coruña
city: Alcorcon
country: Spain
state: Madrid
city: Cartagena
country: Spain
state: Murcia
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Huelva
country: Spain
city: Leon
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Malaga
country: Spain
city: Murcia
country: Spain
city: Murcia
country: Spain
city: Salamanca
country: Spain
city: Sevilla
country: Spain
city: Tarragona
country: Spain
city: Valencia
country: Spain
city: Zaragoza
country: Spain
city: Falun
country: Sweden
city: Kristianstad
country: Sweden
city: Luleå
country: Sweden
city: Sundsvall
country: Sweden
city: Uddevalla
country: Sweden
city: Umea
country: Sweden
city: Uppsala
country: Sweden
city: Tunis
country: Tunisia
city: Ankara
country: Turkey
city: Ankara
country: Turkey
city: Ankara
country: Turkey
city: Bursa
country: Turkey
city: Edirne
country: Turkey
city: Istanbul
country: Turkey
city: Istanbul
country: Turkey
city: Izmir
country: Turkey
city: Kayseri
country: Turkey
city: Kocaeli
country: Turkey
city: Samsun
country: Turkey
city: Blackpool
country: United Kingdom
city: Bournemouth
country: United Kingdom
city: Edinburgh
country: United Kingdom
city: Leeds
country: United Kingdom
city: London
country: United Kingdom
city: Maidstone
country: United Kingdom
city: Manchester
country: United Kingdom
city: Manchester
country: United Kingdom
city: Oxford
country: United Kingdom
city: Romford
country: United Kingdom
city: Somerset
country: United Kingdom
city: Truro
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: