NCT01056510

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.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
357

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Mar 2010

Longer than P75 for phase_4

Geographic Reach
7 countries

84 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 25, 2010

Completed
1 day until next milestone

First Posted

Study publicly available on registry

January 26, 2010

Completed
1 month until next milestone

Study Start

First participant enrolled

March 1, 2010

Completed
4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2014

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

June 25, 2015

Completed
Last Updated

June 25, 2015

Status Verified

June 1, 2015

Enrollment Period

4 years

First QC Date

January 25, 2010

Results QC Date

June 2, 2015

Last Update Submit

June 24, 2015

Conditions

Outcome Measures

Primary Outcomes (1)

  • 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

    The definition of confirmed CR required all of the following criteria as assessed at least 2 months after completion of therapy: peripheral blood lymphocytes less than (\<) 4 times 10\^9 cells per liter (cells/L); absence of significant lymphadenopathy, hepatomegaly, or splenomegaly due to chronic lymphocytic leukemia (CLL) involvement; absence of constitutional symptoms; normal complete blood count (CBC) without need for transfusion or exogenous growth factors, as exhibited by neutrophils at least (\>/=) 1.5 times 10\^9 cells/L, platelets greater than (\>) 100 times 10\^9 cells/L, and hemoglobin \> 11.0 grams per deciliter (g/dL); normocellular bone marrow (BM) aspirate with \< 30 percent (%) lymphocytes; absence of lymphoid nodules; and BM biopsy without CLL activity. The percentage of participants achieving confirmed CR was calculated as the number of participants meeting the above criteria divided by the number of participants analyzed, multiplied by 100.

    At least 2 months after completion of therapy (up to 32 weeks)

Secondary Outcomes (19)

  • Percentage of Participants Achieving Confirmed CR According to IWCLL 2008 Guidelines in the Pooled Population After 6 Cycles of Therapy

    At least 2 months after completion of therapy (up to 32 weeks)

  • Percentage of Participants Achieving Confirmed CR According to IWCLL 2008 Guidelines in the Second-Line Subpopulation After 6 Cycles of Therapy

    At least 2 months after completion of therapy (up to 32 weeks)

  • 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

    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

  • Percentage of Participants by Disease Response Category in the First-Line Subpopulation

    After 6 treatment cycles and at the confirmation of response assessment at least 12 weeks later (up to 36 weeks)

  • Percentage of Participants Experiencing PD or Death in the First-Line Subpopulation

    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)

  • +14 more secondary outcomes

Study Arms (2)

A

EXPERIMENTAL
Drug: bendamustineDrug: rituximab [MabThera/Rituxan]

B

EXPERIMENTAL
Drug: chlorambucilDrug: rituximab [MabThera/Rituxan]

Interventions

90mg/m2 (first-line) or 70mg/m2 (second-line) iv, days 1 and 2 every 4 weeks, cycles 1-6

A

10mg/m2 po days 1-7 every 4 weeks, for up to 12 cycles

B

375mg/m2 iv day 1 of cycle 1, followed by 500mg/m2 iv every 4 weeks cycles 2-6

AB

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (85)

Unknown Facility

Pori, 28500, Finland

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Vantaa, 01400, Finland

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Argenteuil, 95107, France

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Avignon, 84902, France

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Blois, 41016, France

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Bordeaux, 33076, France

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Brest, 29609, France

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La Roche-sur-Yon, 85925, France

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La Tronche, 38700, France

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Le Mans, 72037, France

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Lens, 62307, France

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Limoges, 87042, France

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Lyon, 69003, France

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Marseille, 13915, France

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Mulhouse, 68070, France

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Nice, 06202, France

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Nîmes, 30029, France

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Paris, 75571, France

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Paris, 75651, France

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Perpignan, 66046, France

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Pierre-Bénite, 69495, France

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Salouël, 80480, France

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Coimbra, 3000-075, Portugal

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Lisbon, 1099-166, Portugal

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Lisbon, 1600, Portugal

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Porto, 4200-072, Portugal

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Porto, 4200-319, Portugal

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Vitoria-Gasteiz, Alava, 01009, Spain

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Elche, Alicante, 03203, Spain

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Barcelona, Barcelona, 08025, Spain

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Barcelona, Barcelona, 08035, Spain

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Barcelona, Barcelona, 08036, Spain

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Barcelona, Barcelona, 08907, Spain

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Barcelona, Barcelona, 08916, Spain

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Jerez de la Frontera, Cadiz, 11407, Spain

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Torrelavega, Cantabria, 39300, Spain

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Huelva, Huelva, 21005, Spain

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A Coruña, La Coruña, 15006, Spain

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León, Leon, 24071, Spain

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Alcorcón, Madrid, 28922, Spain

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Madrid, Madrid, 28006, Spain

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Madrid, Madrid, 28041, Spain

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Madrid, Madrid, 28046, Spain

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Madrid, Madrid, 28222, Spain

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Madrid, Madrid, 28905, Spain

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Málaga, Malaga, 29010, Spain

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Cartagena, Murcia, 30203, Spain

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Murcia, Murcia, 30008, Spain

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Murcia, Murcia, 30120, Spain

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Salamanca, Salamanca, 37007, Spain

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Seville, Sevilla, 41009, Spain

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Tarragona, Tarragona, 43007, Spain

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Valencia, Valencia, 46014, Spain

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Zaragoza, Zaragoza, 50009, Spain

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Falun, 79182, Sweden

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Kristianstad, 29185, Sweden

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Luleå, S-971 80, Sweden

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Sundsvall, 85186, Sweden

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Uddevalla, 45180, Sweden

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Umeå, S-90185, Sweden

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Uppsala, 751 85, Sweden

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Tunis, 1008, Tunisia

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Ankara, 06100, Turkey (Türkiye)

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Ankara, 06500, Turkey (Türkiye)

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Ankara, 06620, Turkey (Türkiye)

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Bursa, 16059, Turkey (Türkiye)

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Edirne, 22050, Turkey (Türkiye)

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Istanbul, 34098, Turkey (Türkiye)

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Istanbul, 34390, Turkey (Türkiye)

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Izmir, 35100, Turkey (Türkiye)

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Kayseri, 38039, Turkey (Türkiye)

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Kocaeli, 41400, Turkey (Türkiye)

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Samsun, 55139, Turkey (Türkiye)

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Blackpool, FY3 8NR, United Kingdom

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Bournemouth, BH7 7DW, United Kingdom

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Edinburgh, EH4 2XU, United Kingdom

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Leeds, LS9 7TF, United Kingdom

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London, SE5 9RS, United Kingdom

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Maidstone, ME16 9QQ, United Kingdom

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Manchester, M20 4BX, United Kingdom

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Manchester, OL1 2JH, United Kingdom

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Oxford, OX3 7LJ, United Kingdom

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Romford, RM7 0AG, United Kingdom

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Somerset, TA1 5DA, United Kingdom

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Truro, TR1 3LJ, United Kingdom

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Bendamustine HydrochlorideChlorambucilRituximab

Condition Hierarchy (Ancestors)

Leukemia, B-CellLeukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

ButyratesAcids, AcyclicCarboxylic AcidsOrganic ChemicalsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsBenzimidazolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsAntibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Results Point of Contact

Title
Medical Communications
Organization
Hoffmann-LaRoche

Study Officials

  • Clinical Trials

    Hoffmann-La Roche

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 25, 2010

First Posted

January 26, 2010

Study Start

March 1, 2010

Primary Completion

March 1, 2014

Study Completion

March 1, 2014

Last Updated

June 25, 2015

Results First Posted

June 25, 2015

Record last verified: 2015-06

Locations