Summary
Patients will be randomised in a 1:1 ratio to either arm1 or arm2. Arm1 (standard group): Patients will receive 6 cycles of the escalated BEACOPP regimen as follows- Cyclophosphamide (1250 mg/m^2, IV over 60 minute infusion, day 1); Adriamycin (35 mg/m^2, IV over 30 minute infusion, day 1); Etoposide (200 mg/m^2 per day, IV over 60 minute infusion, day 1 to day 3); Procarbazine (100 mg/m^2 per day, oral capsule, day 1 to day 7); Prednisone (40 mg/m^2 per day, oral tablet, day 1 to day 14); Vincristine (1.4 mg/m^2, IV bolus, day 8); Bleomycin (10 mg/m^2, IV bolus, day 8); Pegylated G-CSF ( 6 mg, subcutaneous injection, day 4). Each cycle is 21 days. Arm2 (experimental group): Patients will receive 6 cycles of the BrECADD regimen as follows- Brentuximab vedotin (1.8 mg/kg, IV over 30 minute infusion, day 1); Cyclophosphamide (1250 mg/m^2, IV over 60 minute infusion, day 2); Adriamycin (40 mg/m^2, IV over 30 minute infusion, day 2); Etoposide (150 mg/m^2 per day, IV over 60 minute infusion, day 2 to day 4); Dacarbazine (250 mg/m^2 per day, IV over 120 minute infusion, day 3 to day 4); Dexamethasone (40 mg/m^2 per day, oral tablet, day 2 to day 5); Pegylated G-CSF (6 mg, subcutaneous injection, day 5). Each cycle is 21 days. In both groups, restaging will take place in the last week of the second treatment cycle (“PET-2â€), at the end of chemotherapy (“PET-6â€), and at the end of radiotherapy if given (restaging after radiotherapy). In both groups, PET-2 is to take place in the last week of the 2nd chemotherapy cycle (between day 17 and day 21) PET-6 is to take place within 3 weeks after day 21 of the 6th chemotherapy cycle. Patients will undergo restaging by FDG-PET with low dose CT, of the whole trunk of the body; images of the lower extremities are only required if a primary tumour was located there. Each restaging will always include an examination of all initially involved lymph nodes or organs using adequate methods. The objective of the PET-2 interim restaging is to document the response to chemotherapy, and to reassess if the patient is still qualified for the trial. The objective of the PET-6 restaging is to document the response to chemotherapy, and to recommend patients for radiotherapy where tumour masses are greater than or equal to 2.5 cm after chemotherapy. If a patient is scheduled for radiotherapy following PET-6 restaging, an additional FDG-PET will take place within 6 weeks after completion of radiotherapy. The decision and organisation of the radiotherapy is up to the discretion of the treating physician on site.