rituximab refractory follicular lymphoma MedDRA version: 16.1 Level: LLT Classification code 10016896 Term: Follicle centre lymphoma diffuse small cell lymphoma NOS System Organ Class: 100000004864
Conditions
Sponsors
VU University Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Biopsy-proven rituximab refractory follicular lymphoma (defined as disease progression while on rituximab maintenance therapy). Patients are required to have received a minimum of 2 infusions of rituximab maintenance therapy and/or be on a maintenance schedule for a minimum of 3 months (measured from the time of first maintenance infusion). Disease progression must have occurred before the last maintenance infusion. •No clinical or pathological evidence of transformation to high-grade or diffuse large B-cell lymphoma (e.g. B symptoms, fast-growing tumour, or increasing lactate dehydrogenase level) •Patients must have radiographically documented measurable disease, defined as 2 or more clearly demarcated lesions with a largest diameter of at least 1.5 cm or 1 clearly demarcated lesion with a largest diameter of at least 2.0 cm by computed tomography scan. All radiology studies must be performed within 14 days prior to registration. •Adult patients, >=18 years of age •Clinical indication for treatment as determined by the “treating physician” •ECOG performance status of 0, 1 or 2. •Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial •Before patient registration, written informed consent must be given according to GCP, and national regulations. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: •Known central nervous system involvement •Concurrent use of other anti-cancer agents •All other lymphoma treatment (except rituximab maintenance therapy) during the last 6 months. •Concurrent use of glucocorticoids (>10mg/day prednisolone or equivalent), or glucocorticoids (>10mg/day prednisolone or equivalent) within 4 weeks of first infusion •Prior use of any investigational monoclonal antibody within 6 months of study start •Prior use of any anti-cancer vaccine •Previous allogeneic stem cell transplantation at any time or previous autologous stem cell transplantation within 6 months of first infusion •More than 1 previous radioimmunotherapy •Radioimmunotherapy within 3 months of first infusion •Other active malignancy or history of other active malignancy. However patients who have been free of malignancy for at least 5 years, or have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible. •Intolerance of exogenous protein administration •Pregnant and breastfeeding women and those of childbearing potential who are not able or willing to use adequate and effective contraception. Definition of adequate and effective contraception: use of two reliable forms of contraception. For women, effective contraception is required to continue for = 12 months after the last dose of obinutuzumab. For men, effective contraception is required to continue for = 3 months after the last dose of obinutuzumab. •Life expectancy 1.5 times the upper limit of normal (unless creatinine clearance normal), or creatinine clearance 2.5 times the upper limit of normal oTotal bilirubin >3 x ULN oNeutrophil count <1.5 x 109/L (unless due to underlying disease, as established by extensive bone marrow involvement) oHemoglobin <8 g/dL (unless due to underlying disease, as established by extensive bone marrow involvement)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To determine the efficacy (defined as overall response) of obinutuzumab monotherapy given in cycles of 4 weekly infusions to rituximab-refractory follicular lymphoma patients ; Secondary Objective: •To determine the efficacy (defined as progression free survival, overall survival, duration of response, duration of stable disease, time to next treatment) of obinutuzumab monotherapy given as 4 weekly infusions to rituximab-refractory follicular lymphoma patients. •To investigate the relationship between tumour uptake on immuno-PET and tumour response to obinutuzumab •To compare tumour uptake using immuno-PET as a novel imaging biomarker to “standard imaging technique” (18F-PET/CT, contrast enhanced CT) •To investigate the biodistribution and dosimetry in normal tissue of 89Zr-obinutuzumab •To determine the value of FDG-PET-CT scanning in response assessment of follicular lymphoma patients •To assess safety data by monitoring all adverse and serious adverse events (AEs/SAEs) according to the NCI CTCAE v.4. ;Primary end point(s): •Overall response using the Revised Response Criteria for Malignant Lymphoma (RRMCML) for disease assessment (10) ;Timepoint(s) of evaluation of this end point: week 10-12 after start study treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Progression-free survival •Overall survival •Duration of response, in responders •Duration of stable disease •Time to next anti-lymphoma treatment •The detection of tumour lesions employing contrast enhanced CT-scan •The detection of tumour lesions employing 18F-FDG-PET •The detection of tumour lesions employing 89Zr-obinutuzumab immuno-PET •The detection of 89Zr-obinutuzumab in normal tissue •The description of safety data: all adverse events and serious adverse events (AEs/SAEs) according to to the NCI CTCAE v.4. ; Timepoint(s) of evaluation of this end point: PFS+duration of response+uration of stable disease +The detection of tumour lesions employing contrast enhanced CT-scan 6,9,12 months Os+time to next treatment: every 2 months up to one year •The detection of tumour lesions employing 18F-FDG-PET: month 6 •The detection of tumour lesions employing 89Zr-obinutuzumab immuno-PET: day 1,4,7 •The detection of 89Zr-obinutuzumab in normal tissue: day 1,4,7 •The description of safety data: every visit | — |
Countries
Netherlands
Contacts
Public ContactTrial office dept. of Haematology
VU University Medical Center
Outcome results
None listed