Health Condition 1: null- Diffuse Large Cell B Cell Lymphoma or Grade 3b Follicular Lymphoma
Conditions
Interventions
Intervention1: Ofatumumab: Four infusions of ofatumumab will be administered as follows: Day 1 (or up to 3 days
prior to Day 1) and Day 8 (±2 days) of cycle 1 of the salvage chemotherapy cycle, and
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Sponsors
GlaxoSmithKline Pharmaceuticals Ltd
Eligibility
Inclusion criteria
Inclusion criteria: 1 CD20 positive DLBCL or grade 3b follicular lymphoma (FL) at original diagnosis If a biopsy or fine needle aspiration (FNA) is performed prior to enrolment to the study it must confirm CD20 positive DLBCL or grade 3b FL Note If evidence emerges that the binding of the immunohistochemical antibody to CD20 can be blocked by rituximab demonstration of CD20 positivity in the repeat biopsy/FNA will not be required 2 Refractory to or relapsed following first-line treatment with rituximab concurrently with anthracycline- or anthracenedione-based chemotherapy Refractory disease must fulfill one of the following continuing partial response (PR) from termination of first-line treatment The lymphoma should be reconfirmed by biopsy (preferred) or FNA however if these procedures are deemed to be inappropriate, then HOVON may determine eligibility following review of the imaging results and disease history Subjects must have received rituximab concurrently with at least 6 cycles of chemotherapy However, subjects with stage I/II disease will be eligible if they have received rituximab concurrently with at least 3 cycles of chemotherapy and definitive involved-field radiation therapy continuing stable disease (SD) from termination of first-line treatment Reconfirmation of the lymphoma by biopsy (preferred) or FNA is recommended but not mandatory Subjects must have received rituximab concurrently with at least 3 cycles of chemotherapy progressive disease (PD) Biopsy or FNA reconfirmation of the lymphoma is recommended but not mandatory Note: Disease response to first-line treatment should be determined according to Revised Response Criteria for Malignant Lymphoma [Cheson 2007] or International Workshop Response criteria for NHL [Cheson 1999] For guidance on the adequacy of dosing of rituximab during first-line therapy refer to the SPM 3 Baseline FDG-PET scans must demonstrate positive lesions compatible with CT defined anatomical tumor sites 4 CT scan showing at least: 2 or more clearly demarcated lesions/nodes with a long axis >1.5cm and short axis >=1.0cm OR 1 clearly demarcated lesion/node with a long axis >2.0cm and short axis >=1.0cm. 5 Age >=18 6 ECOG performance status 0 1 or 2 7 Eligible for high dose chemotherapy and ASCT 8 Resolution of toxicities from first-line therapy to a grade that in the opinion of the investigator does not contraindicate study participation 9 Signed written informed consent
Exclusion criteria
Exclusion criteria: 1 Any previous cancer therapy for the lymphoma, with the exception of First-line treatment with rituximab and an anthracycline- or anthracenedionebased chemotherapy Monotherapy rituximab, dosed prior to first-line rituximab combined with chemotherapy or as maintenance therapy Radiotherapy as part of the first-line treatment plan Radiotherapy to a limited field at a maximum dose of symptoms 2 Received any of the following treatments within two weeks prior to start of study therapy (unless otherwise stated) Anti-cancer cytotoxics (e.g. alkylating agents anti-metabolites purine analogues) Radiotherapy unless it is to a limited field at a maximum dose of control life-threatening symptom 3 Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to enrollment whichever is longer or currently participating in any other interventional clinical study unless in the opinion of the investigator it does not contraindicate participation in this study 4 Planned post-randomisation glucocorticoid therapy unless specified by the protocol administered in doses glucocorticoid-refer to the SPM for glucocorticoid equivalent doses) administered as inhalation therapy for mild COPD or asthma 5 History of significant cerebrovascular disease or event with significant symptoms or sequelae unless in the opinion of the investigator it does not contraindicate participation in the study 6 Clinically significant cardiac disease including unstable angina acute myocardial infarction within six months prior to randomisation congestive heart failure (NYHA III-IV) and arrhythmia unless controlled by therapy with the exception of extra systoles or minor conduction abnormalities, unless in the opinion of the investigator it does not contraindicate participation in the study 7 Significant concurrent, uncontrolled medical condition that in the opinion of the investigator contraindicates participation in this study 8 Known lymphoma involvement of the CNS 9 Known or suspected hypersensitivity to study treatments that in the opinion of the investigator contraindicates their participation 10 Known HIV positivity 11 Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg In addition if negative for HBsAg but HBcAb positive (regardless of HBsAb status) a HB DNA test will be performed and if positive the subject will be excluded
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the progression-free survival (PFS) in subjects receiving ofatumumab in addition to salvage chemotherapy (O-chemo) compared to subjects receiving rituximab in addition to salvage chemotherapy (R-chemo).Timepoint: Long Term Follow-up | — |
Secondary
| Measure | Time frame |
|---|---|
| Changes in health-related quality of life (HRQL) measures.Timepoint: Long Term Follow-up;Event-free survival.Timepoint: Long Term Follow-up;Incidence, severity of adverse events, serious adverse events and other safety. parameters.Timepoint: Long Term Follow-up;Number of subjects completing ASCT.Timepoint: 3 Months Post ASCT Follow-up;Number of subjects with inadequate mobilisation of autologous stem cells (2.0 million CD34+ cells/kg) prior to administration of high dose therapy (HDT).Timepoint: HDT-ASCT Visit;Overall response rate after salvage chemoimmunotherapyTimepoint: 3-Months Follow-up;Overall response rate three months after ASCT.Timepoint: 3 Months Post ASCT Follow-up;Overall survival.Timepoint: Long Term Follow-up;Time to neutrophil and platelet recovery after each cycle of therapy including HDT/ASCT.Timepoint: Long Term Follow-up;To evaluate the following in subjects receiving O-chemo compared to subjects receiving R-chemo: â?¢ PFS in the DHAP subgroupTimepoint: Long Term Follow-up | — |
Countries
Argentina, Austria, Belgium, China, Czech Republic, Denmark, Estonia, Finland, Germany, Greece, Hungary, India, Ireland, Israel, Japan, Netherlands, Norway, Poland, Republic of Korea, Russian Federation, Singapore, Spain, Sweden, Thailand, United Kingdom, United States of America
Contacts
Public ContactKedar Nayak
GlaxoSmithKline Pharmaceuticals Ltd.
Outcome results
None listed