Diffuse Large B-Cell Lymphoma (DLBCL)
Conditions
Sponsors
GlaxoSmithKline Research and Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects eligible for enrolment in the study must meet all of the following 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. Relapse is defined as: • Biopsy (preferred) or FNA confirmed DLBCL or grade 3b FL after a complete response (CR). However, for subjects relapsing during first-line treatment, biopsy/FNA reconfirmation of the lymphoma is recommended but not mandatory. 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. 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. 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. Any previous cancer therapy for the lymphoma, with the exception of: • First-line treatment with rituximab and an anthracycline- or anthracenedione-based 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 =10Gy to control life-threatening 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 =10Gy to control life-threatening symptoms. 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 =1mg/kg/day prednisolone (or equivalent dose of other 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. 12. Active hepatitis C infection. 13. Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis and tuberculosis. 14. Other past or current malignancy unless in the opinion of the investigator it does not contraindicate participation in the study. For example, subjects 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.* 15. Prior treatment with anti-CD20 monoclonal antibodies with the exception of rituximab. 16. Screening laboratory values: • platelets <100x109/L (unless due to lymphoma involvement of the bone marrow) • neutrophils <1.5x109/L (unless due to ly
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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).;Secondary Objective: To evaluate the following in subjects receiving O-chemo compared to subjects receiving R-chemo: • PFS in the DHAP subgroup. • Overall response rate after salvage chemoimmunotherapy. • Overall response rate three months after ASCT. • Event-free survival. • Overall survival. • Number of subjects with inadequate mobilisation of autologous stem cells (<2.0 million CD34+ cells/kg) prior to administration of high dose therapy (HDT). • Changes in health-related quality of life (HRQL) measures • Incidence, severity of adverse events, serious adverse events and other safety parameters. • Number of subjects completing ASCT • Time to neutrophil and platelet recovery after each cycle of therapy including HDT/ASCT.;Primary end point(s): Progression-free survival (PFS). Progression-free survival is defined as the time from randomization until stable disease after two cycles of salvage chemoimmunotherapy, progression or death, whichever occurs first. | — |
Countries
Austria, Belgium, Czech Republic, Denmark, Estonia, Finland, Germany, Greece, Hungary, Ireland, Netherlands, Poland, Spain, Sweden, United Kingdom
Outcome results
None listed