S0816 Fludeoxyglucose F 18-PET/CT Imaging and Combination Chemotherapy With or Without Additional Chemotherapy and G-CSF in Treating Patients With Stage III or Stage IV Hodgkin Lymphoma

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.

DISEASE CHARACTERISTICS:

- Histologically confirmed classical Hodgkin lymphoma (HL) (i.e., nodular sclerosis,
mixed cellularity, lymphocyte-rich, or lymphocyte-depleted)

- Previously untreated stage III or IV disease

- No nodular lymphocyte predominant disease

- Bidimensionally measurable disease

- Adequate biopsy samples from original diagnostic specimen must be available for
pathologic review

- Tissue obtained from core biopsies allowed

- No tissue obtained from needle aspirations or cytologies

- Must have known HIV status

- No multi-drug resistant HIV infection, CD4 counts < 150/μL, or other concurrent
AIDS-defining conditions in HIV-positive patients

- HIV-positive patients with CD4 counts ≥ 150/μL at the time of enrollment OR
documented CD4 count > 250/μL at any time within 8 months prior to HL diagnosis
allowed

- Must have undergone unilateral or bilateral bone marrow biopsy within the past 42 days

- Must have a diagnostic quality CT scan of the chest/abdomen and pelvis AND baseline
FDG-PET scan within the past 28 days

- Combined PET/CT scans required

- No older "stand-alone" FDG-PET scans

- No low-resolution "localization" CT scans as part of a combined PET/CT scans

PATIENT CHARACTERISTICS:

- Zubrod performance status 0-2

- Serum erythrocyte sedimentation rate, lactate dehydrogenase (LDH), hemoglobin,
albumin, white blood cell count (WBC), and lymphocytes measured within the past 28
days

- Serum estradiol (women only), testosterone (men only), follicle stimulating hormone
(FSH) and luteinizing hormone (LH) (both men and women) levels must be drawn within 60
days prior to registration

- Not pregnant or nursing

- Fertile patients must use effective contraception during and for ≥ 6 months after
completion of study therapy

- No significant cardiac abnormalities as assessed by multiple gated acquisition scan
(MUGA) or ECHO AND cardiac ejection fraction ≥ 45% in patients with a history of
hypertension or cardiac symptoms

- Hepatitis B-negative (i.e., hepatitis B surface antigen-negative or anti-hepatitis B
core antigen-negative)

- Patients immune to or immunized against hepatitis B (i.e., anti-hepatitis B
surface antibody-positive) are eligible

- Hepatitis C-negative (i.e., anti-hepatitis C antibody-negative)

- No significant lung disease with abnormal lung function tests (i.e., diffusing
capacity of lung for carbon monoxide (DLCO) > 25% below predicted after correction for
hemoglobin) unless attributable to lymphoma

- No requirement for continuous supplemental oxygen therapy

- No other prior malignancy except adequately treated basal cell or squamous cell skin
cancer, in situ cervical cancer, adequately treated stage I or II cancer from which
the patient is currently in complete remission, or any other cancer from which the
patient has been disease-free for 5 years

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior chemotherapy, radiotherapy, or antibody therapy for lymphoma

- No prior solid organ transplantation