HD17 for Intermediate Stage Hodgkin Lymphoma - Treatment Optimization Trial in the First-Line Treatment of intermediate Stage Hodgkin lymhoma; Therapy stratification by means of FDG-PET

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 current treatment standard for patients with intermediate stage Hodgkin
lymphoma is a combined chemo- and radiotherapy. This kind of treatment provides
excellent cure rates, but is associated with treatment-related late toxicities.
According to present knowledge, these are mainly due to the combined use of
both treatment modalities, so if radiotherapy could be dispensed with, this
would be a significant therapeutic advancement. By using FDG-PET after 4 cycles
of chemotherapy it might be possible to identify those patients in whom
radiotherapy can be omitted.

Also in this trial 30 Gy involved-field radiotherapy, which is
well-established, is compared to involved-node radiotherapy, which marks an
interesting advancement in terms of the target volume definition. It is
expected that acute and late toxicities can be further minimized with this
treatment approach while efficacy will be maintained.
Besides, the trial will show whether radiotherapy can be dispensed within
patients who are PET negative after chemotherapy.

The aim of this trial is to individualize and thus to optimize treatment for
each patient by adapting it to the individual response.
The treatment response is determined by means of FDG-PET after 2 cycles of
escalated BEACOPP + 2 cycles of ABVD.
The aim for patients who show a good response is to reduce the toxicity of
therapy without impairing treatment results. Consequently, in future only those
patients who show an inadequate response to chemotherapy would receive
additional radiotherapy.

IN radiotherapy is introduced to investigate whether this new target volume
definition leads to a reduction in toxicity while maintaining the PFS rate.

Prospective, randomized multicenter study with treatment stratification by
means of FDGPET-scan performed after 4 courses of chemotherapy.

STANDARD ARM:
2 x escalated BEACOPP + 2 x ABVD + 30 Gy IF-RT, independent of the FDG-PET
result


EXPERIMENTAL ARM:
2 x escalated BEACOPP + 2 x ABVD for all patients, then stratification by means
of FDG-PET;
for PET positive patients: + 30 Gy IN-RT
for PET negative patients: no RT


The randomization result will not be disclosed until the results of the
restaging examinations and the FDG*PET assessment by the central PET panel have
been established.

For PET-negative patients after 4 courses of chemotherapy: end of treatment
For PET-positive patients after 4 courses of chemotherapy: 30 Gy Involved Node
Radiotherapy

Those patients in whom radiotherapy is omitted have a higher risk of relapse.
However, from the GHSG*s point of view this is a manageable risk because of the
availability of effective treatments that lead to permanent cure in a major
part of relapsed patients.
Besides, the trial will be monitored regularly regarding imbalances between the
treatment arms in terms of the number of relapsed patients or patients with
primarily progressive disease, and it would be terminated early in case of a
significantly increased number of events.
In summary, from the GHSG*s perspective the potential benefit that may be
gained from the HD17 trial clearly outweighs the risks described above.