BRENTUXIMAB VEDOTIN ASSOCIATED WITH CHEMOTHERAPY IN UNTREATED PATIENTS WITH STAGE I/II UNFAVOURABLE HODGKIN LYMPHOMA - A RANDOMIZED PHASE II LYSA-FIL-EORTC INTERGROUP STUDY
BREACH

Hodgkin Lymphoma (HL) is a neoplasm of lymphoid tissue that is defined
histopathologically by the presence of malignant Hodgkin Reed-Sternberg (RS)
cells. CD30 expression has been well established on RS cells in fresh tumor
biopsies and on established in vitro cell lines.
Chemotherapy alone or combined with radiotherapy produces a durable remission
rate of approximately 70% in patients with newly-diagnosed HL.
Patients with limited stage disease do particularly well, and most of them with
favorable prognostic factors can be cured. The future challenge for this group
of patients is to determine the minimum amount of treatment that is necessary
to achieve cure. Radiotherapy and multi-agent chemotherapy may contribute to
the incidence of late complications that are seen and may be responsible for
excess mortality in this population. Recent studies have shown that the amount
of chemotherapy and the field and dose of radiotherapy can be reduced safely.

Primary objective:
To improve the PET negativity after two cycles of immuno-chemotherapy
Primary efficacy endpoint:
PET 2 assessment according to the five-point scale Deauville criteria (Negative
= 1, 2, 3 and Positive = 4, 5), based on central review.
Secondary objectives:
Secondary efficacy endpoint:
- CR rate (according to Cheson 2007) at the end of treatment
- Progression-free survival (PFS)
- Overall survival
Secondary safety endpoint:
- Toxicity of brentuximab vedotin in combination with combined modality
treatment

Multicentric, open-label, randomized phase II trial
Arm A: 4 cycli van ABVD (elke 28 dagen) Radiotherapie op het einde van de
chemotherapie: 30 Gy INRT zonder boost.
Arm B: 4 cycli van AVD / Brentuximab vedotin (elke 28 dagen) Radiotherapie eind
immuno-chemotherapie: 30 Gy zonder INRT boost.

Arm A:
4 cycles of ABVD (every 28 days) * Radiotherapy at the end of chemotherapy: 30
Gy INRT without boost.
Arm B:
4 cycles of AVD/Brentuximab vedotin (every 28 days) Radiotherapy at the end of
immuno-chemotherapy: 30 Gy INRT without boost.

Physical examination, blood tests, heart and lung-function tests, a CT scan
(with intravenous contrast) and PET scan
Administration of treatments: ABVD (arm A) or AVD + Brentuximab vedotin (arm B)
The rhythm and mode of administration are the same in each arm: by intravenous
infusion in four 28-day cycles, at D1 and D15 of each cycle.
Radiotherapy (RT): This starts from 3 to 4 weeks after the last cycle of
chemotherapy, and will last for about 3 weeks. You get a total standard dose of
30 Gy (Grays), spread over multiple sessions, the areas that were initially
affected by Hodgkin lymphoma.
If the patient is one of the first 21 patients who started the radiotherapy,
the doctor will every week contact him to the visit by the end of treatment to
document all the events that have been observed during the radiotherapy.
The chemotherapy may be associated with known undesirable effects. Nausea and
vomiting, Neurological disorders in the arms or legs, fatigue, gastrointestinal
problems possible risks to the unborn child.