Trial Information

The H10 EORTC/GELA/IIL Randomized Intergroup Trial on Early FDG-PET Scan Guided Treatment Adaptation Versus Standard Combined Modality Treatment in Patients With Supradiaphragmatic Stage I/II Hodgkin's Lymphoma

OBJECTIVES:

Primary

- Evaluate whether chemotherapy alone is as effective, but less toxic, as combined
modality treatment, in terms of progression-free survival (PFS), in patients with
favorable or unfavorable supradiaphragmatic stage I or II Hodgkin's lymphoma who are
fludeoxglucose F 18 positron emission tomography (FDG-PET) scan negative after two
courses of doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine (ABVD).

Secondary

- Evaluate whether early change of chemotherapy from ABVD to escalated cyclophosphamide,
doxorubicin hydrochloride, vincristine, bleomycin, etoposide, procarbazine
hydrochloride, and prednisone (escalated BEACOPP) improves the PFS of patients who are
FDG-PET scan positive after two courses of ABVD.

- Confirm that early response by FDG-PET scan is predictive of the outcome of patients
randomized to the standard treatment arm.

OUTLINE: This is a multicenter, randomized study. Patients are stratified according to
disease prognostic profile (favorable vs unfavorable), participating center, Ann Arbor
clinical stage (I vs II), and availability of a baseline fludeoxyglucose F 18 positron
emission tomography (FDG-PET) scan (yes vs no). Patients are randomized to 1 of 2 treatment
arms.

- Arm I (standard [closed to accrual as of 6/24/2011]): Patients receive ABVD
chemotherapy comprising doxorubicin hydrochloride IV, bleomycin IV or intramuscularly
(IM), vinblastine IV, and dacarbazine IV on days 1 and 15. Treatment repeats every 28
days in the absence of disease progression or unacceptable toxicity. Patients with
favorable prognostic profile receive 3 courses of ABVD. Patients with unfavorable
prognostic profile receive 4 courses of ABVD. Patients undergo FDG-PET scan after
completion of 2 courses of ABVD. Beginning 3-4 weeks after completion of ABVD, patients
undergo involved-node radiotherapy (INRT) 5 days a week for 4-6 weeks.

- Arm II (experimental): Patients receive ABVD as in arm I for 2 courses and then undergo
FDG-PET scan. Further treatment is adapted according to FDG-PET scan result.

- FDG-PET negative: Patients with favorable prognostic profile receive 1 additional
courses of ABVD. Patients with unfavorable prognostic profile receive 2 additional
courses of ABVD. Patients with favorable or unfavorable prognostic profiles
randomized on or after August 9th 2010 who are FDG-PET negative after two courses
of ABVD will receive standard combined modality treatment consisting of ABVD and
INRT as in arm I.

- FDG-PET positive: Patients receive ABVD as in arm I for 2 courses or
intensification to escalated BEACOPP chemotherapy comprising cyclophosphamide IV
and doxorubicin hydrochloride IV on day 1, vincristine IV and bleomycin IV or IM
on day 8, etoposide IV on days 1-3, oral procarbazine hydrochloride on days 1-7,
oral prednisone on days 1-14, and filgrastim (G-CSF) subcutaneously beginning on
day 9 and continuing until blood count recover. Treatment repeats every 21 days
for 2 courses in the absence of disease progression or unacceptable toxicity.
Beginning 3-4 weeks after completion of ABVD or BEACOPP, patients undergo INRT 5
days a week for 4-6 weeks.

After completion of study treatment, patients are followed periodically for at least 10
years.

PROJECTED ACCRUAL: A total of 1,797 patients will be accrued for this study.