Chemotherapy Based on Positron Emission Tomography Scan in Treating Patients With Stage I or Stage II Hodgkin Lymphoma

PRIMARY OBJECTIVES:

I. To determine the progression-free survival (PFS) from enrollment for patients with
non-bulky stage I and II Hodgkin lymphoma.

II. To compare the PFS of patients who are PET positive versus PET negative following 2
cycles of doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine (ABVD).

SECONDARY OBJECTIVES:

I. To evaluate the complete response (CR) rate of patients diagnosed with non-bulky stage I
and II Hodgkin lymphoma following PET response-adapted chemotherapy with or without radiation
therapy.

II. To determine the predictive value of fludeoxyglucose (FDG) uptake using various
semi-quantitative approaches, at baseline, after 2 cycles of AVBD and at completion of
therapy.

III. To determine the predictive value of volumetric changes on computed tomography (CT) vs
2-dimensional (2-D) analyses after 2 cycles and 4 cycles and compare with PET parameters with
and without combination analyses (PET + dedicated CT data).

IV. To compare the predictive value of metabolic parameters/changes that are measured both
visually and semi-quantitatively, International Harmonization Project (IHP) criteria, 2-D and
volumetric CT changes, molecular parameters, and conventional parameters, including
International Prognostic Score (IPS).

V. To assess whether elevated baseline circulating markers of inflammation (including soluble
cluster of differentiation CD30 [sCD]30, soluble CD 163 [CD163], interleukin-10 (IL10),
chemokine (C-C motif) ligand 17 (CCL17), and chemokine (C-C motif) ligand 22 [CCL22])
correlate with clinical response and PFS and PET scan results.

VI. To assess whether persistent or recurrent elevated serial circulating markers of
inflammation (including soluble CD30 [sCD30], soluble CD163 [sCD163], IL10, CCL17, or CCL22)
correlate with relapse/progression or PET scan results.

VII. To confirm independently useful tissue biomarkers for risk stratification in patients
with non-bulky stage I and II Hodgkin lymphoma treated with this regimen.

VIII. To compare mediastinal bulk on standing posterior-anterior (PA) and lateral chest x-ray
(> 0.33 maximum chest diameter) with chest CT (mass > 10 cm).

OUTLINE:

ABVD CHEMOTHERAPY: Patients receive doxorubicin hydrochloride intravenously (IV) over 3-5
minutes, bleomycin sulfate IV over 3-5 minutes, vinblastine IV over 3-5 minutes, and
dacarbazine IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for 2
courses. Patients then undergo PET scan. Patients achieving complete response (CR), partial
response (PR), or stable disease (SD) with a negative PET scan receive 2 additional courses
of ABVD chemotherapy in the absence of disease progression or unacceptable toxicity. Patients
achieving CR, PR, or SD with a positive PET scan proceed to escalated BEACOPP chemotherapy.

ESCALATED BEACOPP* CHEMOTHERAPY: Patients receive doxorubicin hydrochloride IV over 3-5
minutes and cyclophosphamide IV over 60 minutes on day 1, etoposide IV over 45-60 minutes on
days 1-3, procarbazine orally (PO) on days 1-7, prednisone PO on days 1-14, and bleomycin
sulfate IV and vincristine IV on day 8. Treatment repeats every 21 days for 2 courses in the
absence of disease progression or unacceptable toxicity. Within 4-6 weeks after completion of
BEACOPP chemotherapy, patients undergo involved-field radiotherapy (IFRT) 5 days a week for
3½ weeks.

NOTE: * HIV-positive patients receive standard BEACOPP instead of escalated BEACOPP.

Patients undergo fludeoxyglucose F^18 PET/CT scan at baseline, and within 8-10 days after
completion of chemotherapy. Patients also undergo additional PET/CT scans within 3-4 weeks
after completion of ABVD or within 12 weeks after completion of BEACOPP and IFRT. Patients
with a negative PET scan proceed to follow up. Patients with a positive PET scan undergo
biopsy**. Patients with a negative biopsy proceed to follow up, and patients with a positive
biopsy are treated at the discretion of the investigator.

NOTE: ** Patients for whom biopsy is neither clinically appropriate nor medically feasible
proceed to follow-up. Patients for whom biopsy is neither clinically indicated nor medically
appropriate undergo a repeat PET/CT scan after 3 months. If PET/CT scan remains positive,
patients undergo biopsy as above.

After completion of study therapy, patients are followed up every 3 months for 1 year, every
6 months for 2-3 years, and then annually for a maximum of 5 years.

DISEASE CHARACTERISTICS:

- Histologically confirmed* Hodgkin lymphoma

- Clinical stage IA, IB, IIA, or IIB disease according to the modified Ann Arbor
Staging Classification system

- Subclassified according to the WHO modification of the Rye Classification

- "E" extension allowed provided all other criteria have been met NOTE: *Pathology
materials must be submitted within 60 days of study registration. Core-needle
biopsies are acceptable provided they contain adequate tissue for primary
diagnosis and immunophenotyping. Fine-needle aspirates not allowed. If multiple
specimens are available, submit the most recent.

- No nodular lymphocyte-predominant Hodgkin lymphoma

- No mediastinal mass > 0.33 maximum intrathoracic diameter by standing postero-anterior
chest x-ray or peripheral or retroperitoneal adenopathy > 10 cm in its largest
diameter

- Measurable disease by physical examination or imaging studies

- Any tumor mass measurable in two dimensions and > 1 cm (or 1.5 cm if 0.5 cm
slices are used, as in spiral CT scans) allowed

- Lesions that are considered intrinsically non-measurable include:

- Bone lesions

- Leptomeningeal disease

- Ascites

- Pleural/pericardial effusion

- Lymphangitis cutis/pulmonis

- Abdominal masses that are not confirmed and followed by imaging techniques

- Cystic lesions

- Lesions that are situated in a previously irradiated area

PATIENT CHARACTERISTICS:

- Performance status 0-2

- ANC ≥ 1,000/μL

- Platelet count ≥ 100,000/μL

- Serum creatinine ≤ 2 mg/dL

- Bilirubin ≤ 2 mg/dL

- AST ≤ 2 times upper limit of normal

- LVEF normal by ECHO or MUGA

- DLCO ≥ 60% with no symptomatic pulmonary disease

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Patients with known HIV allowed provided they have CD4 counts ≥ 350/mcL

- Patients must not have multi-drug resistant HIV infections (i.e., concurrent
AIDS-defining conditions)

- An HIV test is required for patients with a history of IV drug abuse or any
behavior associated with an increased risk of HIVinfection

- No "currently active" second malignancy other than nonmelanoma skin cancers

- Patients are not considered to have a "currently active" malignancy provided they
have completed therapy and are considered by their physician to be at < 30% risk
of relapse

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior chemotherapy or radiotherapy for Hodgkin lymphoma

- 1 course of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) allowed
and will be considered the first course