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Health Condition(s) or Problem
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Non-Hodgkin's Lymphoma
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Lay Summary
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This open-label, randomized study will assess the efficacy and safety of obinutuzumab
(RO5072759) in combination with chemotherapy compared to MabThera/Rituxan (rituximab) with
chemotherapy followed by obinutuzumab or MabThera/Rituxan maintenance in patients with
untreated advanced indolent non-Hodgkin's lymphoma. After the end of the induction period,
patients achieving response (CR or PR) will go on to a maintenance period thereby continuing
on their randomized antibody treatment alone every 2 months until disease progression for a
total of 2 years. Anticipated time on study treatment is up to approximately 2.5 years.
After maintenance or observation patients will be followed for 5 years until progression.
After progression, patients will be followed for new anti-lymphoma therapy and overall
survival until the end of the study.
(from ClinicalTrials.gov)
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Who can enter the trial
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Inclusion Criteria:
- Adult patients, >/= 18 years of age
- CD20-positive indolent B-cell non-Hodgkin's lymphoma (follicular lymphoma or splenic,
nodal or extranodal marginal zone lymphoma)
- Stage III or IV disease, or Stage II bulky disease (defined as tumour diameter >/= 7
cm), requiring treatment
- For patients with follicular lymphoma: requirement for treatment according to GELF
criteria
- For patients with symptomatic marginal zone lymphoma: disease that is de novo or has
relapsed following local therapy (i.e. surgery or radiotherapy) and requires therapy
as assessed by the investigator
- At least one bi-dimensionally measurable lesion (>2 cm in its largest dimension by CT
scan or MRI)
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
- Adequate hematologic function
Exclusion Criteria:
- Central nervous system lymphoma, leptomeningeal lymphoma, or histological evidence of
transformation to a high-grade or diffuse large B-cell lymphoma
- Grade 3b follicular lymphoma, small lymphocytic lymphoma or Waldenström's
macroglobulinaemia
- Ann Arbor Stage I disease
- History of severe allergic or anaphylactic reactions to monoclonal antibody therapy,
known hypersensitivity to any of the study drugs or sensitivity to murine products,
or history of sensitivity to mannitol
- For patients with follicular lymphoma: prior treatment for non-Hodgkin's lymphoma
with chemotherapy, immunotherapy, or radiotherapy
- For patients with non-follicular lymphoma: prior treatment with chemotherapy or
immunotherapy
- Regular treatment with corticosteroids during the 4 weeks prior to the start of Cycle
1
- Evidence of significant, uncontrolled concomitant diseases that could affect
compliance with the protocol or interpretation of results
- For patients who will be receiving CHOP: LVEF <50% by MUGA scan or echocardiogram
- History of prior malignancy with the exception of curatively treated basal or
squamous cell carcinoma of the skin and low-grade in situ carcinoma of the cervix
- Known active infection, or major episode of infection within 4 week prior to the
start of Cycle 1
- Vaccination with a live vaccine within 28 days prior to randomization
- Recent major surgery (within 4 weeks prior to start of Cycle 1), other than for
diagnosis
- Abnormal laboratory values as defined by protocol for creatinine, creatinine
clearance, AST or ALT, total bilirubin, INR, PTT or aPPT, unless these abnormalities
are due to underlying lymphoma
- Positive as per protocol definition for HIV, HTLV1, hepatitis C or chronic hepatitis
B
- Pregnant or lactating women
- Life expectancy < 12 months
- Participation in another clinical trial with drug intervention within 28 days prior
to start of Cycle 1 and during study
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Who cannot enter the trial
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Inclusion Criteria:
- Adult patients, >/= 18 years of age
- CD20-positive indolent B-cell non-Hodgkin's lymphoma (follicular lymphoma or splenic,
nodal or extranodal marginal zone lymphoma)
- Stage III or IV disease, or Stage II bulky disease (defined as tumour diameter >/= 7
cm), requiring treatment
- For patients with follicular lymphoma: requirement for treatment according to GELF
criteria
- For patients with symptomatic marginal zone lymphoma: disease that is de novo or has
relapsed following local therapy (i.e. surgery or radiotherapy) and requires therapy
as assessed by the investigator
- At least one bi-dimensionally measurable lesion (>2 cm in its largest dimension by CT
scan or MRI)
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
- Adequate hematologic function
Exclusion Criteria:
- Central nervous system lymphoma, leptomeningeal lymphoma, or histological evidence of
transformation to a high-grade or diffuse large B-cell lymphoma
- Grade 3b follicular lymphoma, small lymphocytic lymphoma or Waldenström's
macroglobulinaemia
- Ann Arbor Stage I disease
- History of severe allergic or anaphylactic reactions to monoclonal antibody therapy,
known hypersensitivity to any of the study drugs or sensitivity to murine products,
or history of sensitivity to mannitol
- For patients with follicular lymphoma: prior treatment for non-Hodgkin's lymphoma
with chemotherapy, immunotherapy, or radiotherapy
- For patients with non-follicular lymphoma: prior treatment with chemotherapy or
immunotherapy
- Regular treatment with corticosteroids during the 4 weeks prior to the start of Cycle
1
- Evidence of significant, uncontrolled concomitant diseases that could affect
compliance with the protocol or interpretation of results
- For patients who will be receiving CHOP: LVEF <50% by MUGA scan or echocardiogram
- History of prior malignancy with the exception of curatively treated basal or
squamous cell carcinoma of the skin and low-grade in situ carcinoma of the cervix
- Known active infection, or major episode of infection within 4 week prior to the
start of Cycle 1
- Vaccination with a live vaccine within 28 days prior to randomization
- Recent major surgery (within 4 weeks prior to start of Cycle 1), other than for
diagnosis
- Abnormal laboratory values as defined by protocol for creatinine, creatinine
clearance, AST or ALT, total bilirubin, INR, PTT or aPPT, unless these abnormalities
are due to underlying lymphoma
- Positive as per protocol definition for HIV, HTLV1, hepatitis C or chronic hepatitis
B
- Pregnant or lactating women
- Life expectancy < 12 months
- Participation in another clinical trial with drug intervention within 28 days prior
to start of Cycle 1 and during study
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What will happen
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Drug; RO5072759; 1000 mg iv on Days 1, 8 and 15 of Cycle 1 and on Day 1 of Cycles 2-8 (21-day cycles) or Cycles 2-6 (28-day cycles); followed by 1000 mg iv every 2 months in responders until disease progression, for up to 2 years; B; GA101; Drug; rituximab [MabThera/Rituxan]; 375 mg/m2 iv on Day 1 of Cycles 1-8 (21-day cycles) or Cycles 1-6 (28-day cycles); followed by 375 mg/m2 iv every 2 months in responders until disease progression, for up to 2 years; A; Drug; chemotherapy; CHOP (6 cycles of 21 days), CVP (8 cycles of 21 days), Bendamustine (6 cycles of 28 days). Patients with follicular lymphoma are receiving either CHOP, CVP or Bendamustine as background chemotherapy as selected by each participating site at study start. Background chemotherapy for patients with non-follicular lymphoma will be chosen by the site individually for each patient.; A; B
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Primary aim
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Progression-free survival in patients with follicular lymphoma, investigator-assessed according to the Revised Response Criteria for Malignant Lymphoma
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Secondary Aim
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Progression-free survival in the overall study population, investigator-assessed; up to approximately 7.5 years; No; Progression-free survival, Independent Review Committee - assessed; up to approximately 7.5 years; No; Response (overall response and complete response), investigator-assessed; 168 days; No; Response (overall response and complete response), Independent Review Committee - assessed; 168 days; No; Overall survival; up to approximately 10.7 years; No; Event-free survival; up to approximately 7.5 years; No; Disease-free survival; up to approximately 7.5 years; No; Duration of response; up to approximately 7.5 years; No; Time to next anti-lymphoma treatment; up to approximately 10.7 years; No; Safety: Incidence of adverse events; up to approximately 10.7 years; No; Patient-reported outcomes (Functional Assessment of Cancer Therapy for Lymphoma scale, EuroQol EQ-5D questionnaire); up to approximately 7.5 years; No; Medical resource utilization (hospitalizations, subsequent drug therapies, medical and surgical procedures); up to approximately 7.5 years; No
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Participant Information Sheet
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Sorry, not currently available
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Website
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Sorry, not currently available
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Recruitment Status
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Recruiting
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Nation
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Scotland, England, Wales
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Location
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Aberdeen, Birmingham, Bournemouth, Bristol, Cambridge, Canterbury, Cardiff, Cottingham, Edinburgh, Glasgow, Great Yarmouth, Harlow, Leeds, Leicester, London, Manchester, Norwich, Nottingham, Oxford, Portsmouth, Southampton, Sutton, Swansea, Swindon, Truro
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