Response-Based Therapy Assessed By PET Scan in Treating Patients With Bulky Stage I and Stage II Classical Hodgkin Lymphoma

This is single-arm phase II clinical trial of response-adapted therapy based on PET for bulky
stage I and stage II Hodgkin lymphoma. A maximum of 123 patients will be entered to the
study. The primary outcome of this study is progression-free survival (PFS), defined as the
time from study entry to disease progression or death.

Primary Objective:

To determine the progression-free survival (PFS) at 36 months from enrollment for patients
with bulky stage I and II Hodgkin lymphoma. All patients will begin treatment with ABVD.
Patients who are PET negative after 2 cycles of chemotherapy will receive 6 cycles of ABVD
without radiotherapy. Patients who are PET positive after 2 cycles of ABVD will then receive
4 cycles of escalated BEACOPP followed by IFRT. A comparison will be made of the 36-month PFS
between patients who are PET positive and those who are PET negative following 2 cycles of
ABVD.

Secondary Objectives:

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

2. To determine the predictive value of FDG uptake using various semiquantitative
approaches, at baseline, after 2 cycles of ABVD and at completion of therapy.

3. To determine the predictive value of volumetric vs. 2 dimensional (2-D) measurement
changes on CT between baseline and after 2 cycles, at the end of chemotherapy (PET
negative patients only) and after RT (PET positive patients only) and compare with PET
parameters.

4. To determine if changes in both qualitative and semiquantitative FDG-PET findings
between baseline and after cycle 2, at end of chemotherapy (PET negative patients only)
and after RT (PET positive patients only) with combination analyses with incorporating
changes obtained from dedicated CT scans, correlate with response and PFS.

5. To compare the predictive value of both qualitative and semiquantitative FDG-PET
changes, 2-D and volumetric CT changes, and combinatorial analyses (PET+dedicated CT
data) with molecular parameters, and conventional parameters, including IPS.

6. To assess whether elevated baseline serum soluble CD30 (sCD30), IL10, CCL17, and CCL22
correlate with clinical response and PFS.

7. To assess whether persistent or recurrent elevation of serial serum sCD30, IL10, CCL17,
or CCL22 correlate with relapse/progression or PET scan results.

8. To confirm independently useful tissue biomarkers (bcl-2, MAL, FOXP3, CD68, GzB) for
risk stratification in patients with bulky stage I and II Hodgkin lymphoma treated with
this regimen.

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

After completion of study treatment, patients are followed up every 3 months for 1 year,
every 6 months for 2-3 years, and then once a year for a maximum of ten years from the time
of entry on the study.

1. Documentation of Disease:

- Histologically documented Hodgkin lymphoma subclassified according to the WHO
modification of the Rye Classification and staged according to the modified Ann
Arbor Staging Classification system.

- Patients must have clinical stage IA, IB, IIA or IIB.

- Patients with "E" extensions will be eligible if all other criteria have
been met.

- Nodular lymphocyte predominant Hodgkin lymphoma is excluded.

- Core needle biopsies are acceptable if they contain adequate tissue for
primary diagnosis and immunophenotyping. Fine needle aspirates are not
acceptable. If multiple specimens are available, please submit the most
recent. Failure to submit pathology materials within 60 days of patient
registration will be considered a major protocol violation.

- Patients must have a mediastinal mass > 0.33 maximum intrathoracic diameter on
standing postero-anterior chest x-ray or mass measuring > 10 cm in its largest
diameter.

2. Second Malignancy: No "currently active" second malignancy other than non-melanoma
skin cancers. Patients are not considered to have a "currently active" malignancy if
they have completed therapy and are considered by their physician to be at less than
30% risk of relapse.

3. Prior Therapy - Patients may have had one cycle only of ABVD prior to enrolling on
study. No other prior treatment (chemotherapy or radiation therapy) for Hodgkin
lymphoma is allowed. If patient has had one cycle of ABVD, in order to be eligible to
enroll on CALGB 50801, the patient must have had all of the following tests prior to
starting the first cycle of ABVD:

- LVEF by ECHO or MUGA

- PFTs (including DLCO/FVC)CT scan (neck*, chest, abdomen, pelvis)

- FDG-PET/CT scan

- Chest X-ray, PA & Lateral

- CBC, differential, platelets

- ESR

- Serum creatinine

- Glucose

- AST

- Alkaline phosphatase

- Bilirubin

- LDH

Patients with a negative FDG-PET/CT scan do not need to have had a dedicated neck CT
scan prior to starting the previous cycle of ABVD.

4. ECOG Performance status 0-2.

5. LVEF and DLCO - LVEF by ECHO or MUGA within institutional normal limits unless thought
to be disease related. DLCO ≥ 60% with no symptomatic pulmonary disease unless thought
to be disease related.

6. HIV Infection - Patients with known HIV must have a CD4 count > 350 and be on
concurrent antiretrovirals. Patients with a history of intravenous drug abuse or any
behavior associated with an increased risk of HIV infection should be tested for
exposure to the HIV virus. An HIV test is not required for entry on this protocol, but
is required if the patient is perceived to be at risk.

7. Pregnancy Restrictions - Non-pregnant and non-nursing. Due to the teratogenic
potential of the agents used in this study, pregnant or nursing women may not be
enrolled. Women and men of reproductive potential should agree to use an effective
means of birth control.

8. Age Restricitions - Age 18 - 60 years

9. Initial Required Laboratory Data:

- ANC ≥ 1000/μL

- Platelet count ≥ 100,000/μL

- Serum Creatinine ≤ 2 mg/dL

- Bilirubin* ≤ 2 x upper limit of normal

- AST ≤ 2 x upper limit of normal* - In the absence of Gilbert's disease