Study design/treatment schema. (A) Using a standard 3 + 3 design, the B-cell malignancy and T-cell malignancy dose escalations proceeded separately. Patients who did not complete the multidose phase for reasons other than DLT were replaced as necessary. The B-cell malignancy dose escalation completed through the maximum planned dose level (10 mg/kg). After the B-cell malignancy dose escalation component of the study, an expansion cohort was enrolled to further explore the clinical and biological activity of varlilumab (at 0.3 mg/kg every 3 weeks) in patients with Hodgkin lymphoma. The study was closed after treatment of 4 patients in the Hodgkin lymphoma expansion cohort and 5 patients at the 3 mg/kg dose level in the T-cell malignancy dose-escalation phase. (B) During the dose-escalation phase, varlilumab (represented by red circles) was initially administered as a single dose with 28-day observation. Additional multidose treatment (4 weekly doses with a 4-week observation) and retreatment (up to 4 additional cycles, each consisting of 4 weekly doses with an 8-week observation) were allowed for patients who had not experienced progressive disease or DLT. Patients in the Hodgkin lymphoma expansion cohort received varlilumab at 0.3 mg/kg, every 3 weeks (up to 5 cycles, each consisting of 4 doses). Diagnostic imaging and restaging were repeated every 12 weeks (as indicated by asterisks).