HD21 for advanced stages: Treatment optimization trial in the first-line treatment of advanced stage Hodgkin lymphoma; comparison of 4-6 cycles of escalated BEACOPP with 4-6 cycles of BrECADD; a randomized phase III trial

The German Hodgkin Study Group Center (GHSG) in Cologne is responsible for
developing trials to improve the treatment of Hodgkin lymphoma.
Improvements in radiotherapy and the introduction of polychemotherapy have
contributed to the development of an incurable malignant disease into an
oncological disease in adults that actually has the best prognosis of all.
Relevant improvements in diagnostics and treatment are based on a stringent
implementation of quality standards in the areas of pathology, radiology,
nuclear medicine, radiotherapy and chemotherapy.

The standard treatment for patients with advanced stage is 4- 6 coureses of
escalated BEACOPP chemotherapy every 3 weeks, followed by radiotherapy, when
necessary.
This standard treatment is an intensive treatment with both acute and long term
toxicity.

Therefore the GHSG had started this new trial to prove that the new
chemotherapy regimen, BrECADD, is non-inferior to BEACOPP as first line
treatment in advanced stage classical Hodgkin Lymphoma patients up to 60 years.
The combination of conventional chemotherapy with brentuximab vedotin is
designed to reduce the doses of certain conventional cytostatics in order to
reduce the rate of adverse events while maintaining an equally good response to
treatment.

This study has been transitioned to CTIS with ID 2024-518022-33-00 check the CTIS register for the current data.

primary objective of the trial is to demonstrate non-inferior efficacy of 4-6
cycles of BrECADD compared to 4-6 cycles of escalated BEACOPP, each followed by
radiotherapy on PET-positive residual lesions, in terms of progression free
survival (efficacy objective).

If non-inferior efficacy can be shown, the co-primary objective is to further
demonstrate reduced toxicity of the BrECADD treatment compared to the escalated
BEACOPP treatment measured by treatment related morbidity (TRMB objective).

Open label, prospective, multicenter trial with two parallel groups and central
statified randomization (minimization method).


Amendment March 2020: new cohort in this trial: older patients between 61-75
years.

Patients are randomized to receive either 4-6 cycles of escalated BEACOPP
regimen (standard group) or 4-6 cycles of BrECADD (experimental group).
After the first two cycles, a restaging is performed by contrast-enhanced
computed tomography (ceCT) and FDG PET/CT in all patients in order to guide
response-adapted continuation of therapy consisting of 4 or only 2 additional
cycles of randomized chemotherapy in case of a PET positive or negative staging
result, respectively.

So patients with negative PET-CT-scan after 2 cycles, will receive additional 2
cycles of chemotherapy.
Patients with a positive PET-CT-scan after 2 cycles, will receive 4 cycles of
chemotherapy.

A second restaging will be performed after completion of chemotherapy; Patients
with PET-positive residual disease will receive local irradiation, while
patients in complete remission do not receive radiotherapy.

Amendment March 2020: all patients in the elderly cohort receive PET guided
treatment with 4- 6 cycles of BrECADD +/- RT.

The benefit from participating in this trial is the chance of being treated
with a new treatment approach that we hope to cause less side-effects compared
to the current standard therapy.
The results of this trial may provide valuable knowledge for the treatment of
Hodgkin Lymphoma in future.
However, it cannot be guaranteed that a patient will benefit from participating
in this trial, and it cannot be ruled out with absolute certainty that
participation in this trial, will not impair the success of the therapy in the
long run.

Patients may suffer from side effects. Qualtiy of Life investigations can be
part of the trial for a certain amount of patients.