Trial Information

A Phase II Trial of Response-Adapted Therapy of Stage III-IV Hodgkin Lymphoma Using Early Interim FDG-PET Imaging

OBJECTIVES:

Primary

- To estimate the 2-year progression-free survival (PFS) of HIV-negative patients with
stage III-IV Hodgkin lymphoma treated with response-adapted therapy based on
fludeoxyglucose F 18 (FDG)-PET imaging after 2 courses of doxorubicin hydrochloride,
bleomycin, vinblastine, and dacarbazine (ABVD).

- To estimate the 2-year PFS of patients who are PET-positive after treatment with 2
courses of ABVD and an escalated dose regimen comprising cyclophosphamide, doxorubicin
hydrochloride, etoposide, vincristine sulfate, bleomycin, procarbazine hydrochloride,
and prednisone (BEACOPP).

Secondary

- To estimate the 2-year overall survival (OS) of patients treated with these regimens.

- To estimate the response rate (i.e., complete and partial responses) in patients
treated with these regimens.

- To evaluate the toxicity of these response-adapted regimens.

- To document the feasibility of centralized, real-time review of FDG-PET imaging for
U.S. cooperative group studies.

- To prospectively evaluate the overall response rate, complete response rate, PFS, and
OS of HIV-positive patients treated with these response-adapted regimens.

OUTLINE: This is a multicenter study.

All patients undergo baseline whole-body fludeoxyglucose F 18 (FDG)-PET/CT imaging before
beginning chemotherapy. Patients then receive doxorubicin hydrochloride IV, bleomycin IV,
vinblastine IV, and dacarbazine IV (ABVD) on days 1 and 15. Treatment repeats every 28 days
for up to 2 courses in the absence of disease progression or unacceptable toxicity. Between
days 22 and 25 of course 2, patients undergo a second FDG-PET/CT scan to assess response.
Subsequent therapy is based on FDG-PET/CT scan results. Patients are stratified according to
FDG-PET positivity (yes vs no). Patients who are FDG-PET-negative continue treatment with
ABVD for up to 4 additional courses in the absence of disease progression or unacceptable
toxicity. Patients who are FDG-PET-positive are then further stratified according to HIV
positivity (yes or no) and receive 1 of the following treatment regimens:

- Escalated-dose BEACOPP chemotherapy: HIV-negative patients receive escalated-dose
BEACOPP chemotherapy comprising doxorubicin hydrochloride IV and cyclophosphamide IV on
day 1, etoposide IV on days 1-3, oral procarbazine hydrochloride on days 1-7, oral
prednisone on days 1-14, and bleomycin IV and vincristine IV on day 8. Patients receive
filgrastim (G-CSF) subcutaneously on days 8-14. Treatment repeats every 21 days for up
to 6 courses in the absence of disease progression or unacceptable toxicity.

- Standard-dose BEACOPP chemotherapy: HIV-positive patients receive standard dose BEACOPP
chemotherapy comprising doxorubicin hydrochloride IV and cyclophosphamide IV on day 1,
etoposide IV on days 1-3, oral procarbazine hydrochloride on days 1-7, oral prednisone
on days 1-14, and bleomycin IV and vincristine IV on day 8. Treatment repeats every 21
days for up to 6 courses in the absence of disease progression or unacceptable
toxicity.

Six to eight weeks after completion of chemotherapy, patients undergo a post-treatment
FDG-PET/CT scan.

Some patients may undergo bone marrow biopsy at 1 month after the last course of
chemotherapy.

After completion of study treatment, patients are followed up periodically for 7 years.