The main objective of this trial is to assess whether treatment adaptation based on a very early FDG-PET/CT results in improved efficacy while minimizing treatment toxicity in advanced stage Hodgkin Lymphoma (HL) patients treated with brentuximab vedotin (BV)-containing regimens.
This single-arm phase II study investigates the value of early FDG-PET-response adapted BV-based therapy for advanced HL. All patients will receive one cycle of BrAVD followed by an FDG-PET/CT. Patients with a negative early FDG-PET(Deauville score 1-3) will continue with five more BrAVD cycles (total six cycles) while patients with a positive FDG-PET should shift to six cycles of BrECADD. The hypothesis is that the efficacy will be comparable to the efficacy of BEACOPPesc and BrECADD, while using the intensive chemotherapy regimen only for those patients who do not achieve a negative FDG-PET after one cycle. The choice to assess the treatment sensitivity by PET after a single cycle of BrAVD is based on results from a recent international multicenter study comparing FDG-PET/CT after one and two cycles of ABVD chemotherapy in HL. There is no reason to suspect that FDG-PET1 should be less prognostic after BrAVD than after ABVD. With this trial, the investigators believe they can add important information about the optimal treatment of BV-containing first-line treatment for advanced HL, and thus answer important therapeutic questions that are likely to otherwise remain unanswered even after the Echelon-1 and HD21 trials reach mature results. This relatively large single-arm phase II trial of 150 patients will allow a meaningful comparison with the BrAVD and BrECADD regimens based on modified progression-free survival (primary endpoint) and progression-free survival (secondary endpoint) respectively.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
150
For PET positive (score of 4-5 following Deauville Criteria) patients: Brentuximab vedotin is administered as an IV infusion over a period of 30 minutes at 1.8 mg/kg on day 1, every 3 weeks (6 cycles); For PET negative (score of 1-3 following Deauville Criteria) patients: Brentuximab vedotin is administered as an IV infusion over a period of 30 minutes at 1.2 mg/kg on day 1 and 15, every 4 weeks (5 cycles)
For PET positive (score of 4-5 following Deauville Criteria) patients: Adriamycin is administered as an IV infusion over a period of 15 minutes at 40 mg/m² on day 2, every 3 weeks (6 cycles); For PET negative (score of 1-3 following Deauville Criteria) patients: Adriamycin is administered as an IV infusion over a period of 15 minutes at 25 mg/m² on day 1 and 15, every 4 weeks (5 cycles)
ZNA Stuivenberg
Antwerp, Belgium
Universitair Ziekenhuis Antwerpen
Edegem, Belgium
Modified Progression-free Survival (mPFS) Rate at 2 Years
Modified PFS (mPFS) is defined as the time interval between the date of treatment start and the date of the first of: * Progressive disease (PD) * Start of new treatment for Classical Hodgkin Lymphoma (cHL) when not in Complete Response at the end of protocol treatment; in this case, the date of mPFS is the date of the FDG-PET/CT scan at the end of protocol treatment. Switching therapy prior to end of protocol treatment for reasons other than Progressive Disease is not considered an event for mPFS. "End of protocol treatment" refers to completion of the planned protocol treatment with no more than 1 missed cycle, including radiotherapy on PET positive lesions if administered * Death due to any cause
Time frame: 2 years from the date of treatment start
Proportion of Patients With a Negative FDG-PET
It will be assessed how many patients have a negative FDG-PET image when taken at the end of their first cycle of BrAVD. The BrAVD cycle lasts 4 weeks.
Time frame: At day 22 to 23 from start of treatment (day 1 = date of start of treatment)
Progression-free Survival (PFS) Rate at 2 Years
Progression-free survival
Time frame: 2 years from the date of treatment start
Overall Survival Rate at 2 Years
Overall survival
Time frame: 2 years from the date of treatment start
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
For PET negative (score of 1-3 following Deauville Criteria) patients: Vinblastine is administered as an IV infusion over a period of 15 minutes at 6mg/m² on day 1 and 15, every 4 weeks (5 cycles)
For PET positive (score of 4-5 following Deauville Criteria) patients: Dacarbazine is administered as an IV infusion over a period of 60 minutes at 250 mg/m² on day 3 and 4, every 3 weeks (6 cycles); For PET negative (score of 1-3 following Deauville Criteria) patients: Dacarbazine is administered as an IV infusion over a period of 60 minutes at 375 mg/m² on day 1 and 15, every 4 weeks (5 cycles)
For PET positive (score of 4-5 following Deauville Criteria) patients: Etoposide is administered as an IV infusion over a period of 60 minutes at 150 mg/m² on day 2,3 and 4, every 3 weeks (6 cycles)
For PET positive (score of 4-5 following Deauville Criteria) patients: Cyclophosphamide is administered as an IV infusion over a period of 30 minutes at 1250 mg/m² on day 2, every 3 weeks (6 cycles)
Patients with residual lymphoma mass(es) showing metabolic activity of Deauville score 4 or 5 after completion of chemotherapy will be offered consolidation radiotherapy.
U.Z. Leuven - Campus Gasthuisberg
Leuven, Belgium
University Hospitals Copenhagen - Rigshospitalet
Copenhagen, Denmark
Amsterdam UMC - Locatie AMC
Amsterdam, Netherlands
Deventer Ziekenhuis
Deventer, Netherlands
University Medical Center Groningen
Groningen, Netherlands
Medisch Centrum Leeuwarden-Zuid
Leeuwarden, Netherlands
Haaglanden Medisch Centrum (HMC) - Haaglanden MC - locatie Antoniushove
Leidschendam, Netherlands
Radboudumc - Radboud University Medical Center Nijmegen
Nijmegen, Netherlands
...and 6 more locations