Chemotherapy Based on PET Scan in Treating Patients With Stage I or Stage II Hodgkin Lymphoma
Chemotherapy Based on PET Scan in Treating Patients With Stage I or Stage II Hodgkin Lymphoma
RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride, bleomycin sulfate,
 vinblastine, dacarbazine, cyclophosphamide, etoposide, procarbazine hydrochloride,
 vincristine sulfate, and prednisone, work in different ways to stop the growth of cancer
 cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses
 high-energy x rays to kill cancer cells. Giving combination chemotherapy together with
 radiation therapy may kill more cancer cells. Comparing results of imaging procedures, such
 as PET scans and CT scans, done before, during, and after chemotherapy may help doctors
 predict a patient's response to treatment and help plan the best treatment.

 PURPOSE: This phase II clinical trial studies how well chemotherapy based on PET/CT scan
 works in treating patients with stage I or stage II Hodgkin lymphoma.
OBJECTIVES:

 Primary

 -  To evaluate the progression-free survival (PFS) at 36 months following registration for
 patients who are positron emission tomography (PET) negative after 2 courses of ABVD,
 and receive 4 additional courses of doxorubicin hydrochloride, bleomycin sulfate,
 vinblastine, and dacarbazine (ABVD) followed by involved-nodal radiotherapy [INRT] of
 30-30.6 Gy.

 Secondary

 -  To evaluate the PET-negative rate after 2 courses of ABVD chemotherapy in patients with
 stage I/II Hodgkin lymphoma with bulky mediastinal disease.

 -  To evaluate the PFS at 36 months for patients who are PET positive after 2 courses of
 chemotherapy and receive 4 courses of escalated bleomycin sulfate, etoposide,
 doxorubicin hydrochloride, cyclophosphamide, vincristine sulfate, procarbazine
 hydrochloride, and prednisone (BEACOPP) followed by INRT of 30-30.6 Gy.

 -  To evaluate the complete response (CR) rate and overall survival (OS) for PET-positive
 and PET-negative patients after 2 courses of ABVD.

 -  To identify sites of relapse following combined-modality therapy (CMT) for patients with
 large mediastinal adenopathy and correlate with RT fields.

 -  To assess toxicity on both arms of study.

 -  To assess reproductive function at baseline and at 3 years after ABVD or escalated
 BEACOPP with specific serum markers.

 -  To bank serum and plasma at baseline and selected time points to assess the prognostic
 value of various markers such as, but not limited to, SCD30, IL10, CCL17, CCL22, and
 MDC.

 -  To create tissue microarrays (TMAs) from patient tumor blocks for future biomarker
 assessment including, but not limited to, bcl-2, FOXP3, and macrophage content.

 -  To measure serum TARC levels pre-treatment and post two courses of ABVD and correlate
 with PET-CT findings (performed at same time points) and 3 year PFS.

 Tertiary

 -  To assess the predictive value of fludeoxyglucose F 18 (18FDG) uptake, as measured by
 semi-quantitative measurements including standard uptake variables (SUVs), with respect
 to response at the end of chemotherapy and PFS.

 -  To compare the predictive value for response and PFS of FDG uptake alone to that of FDG
 uptake in combination with CT size change information.

 -  To compare the predictive value for response and PFS of FDG uptake alone to that of FDG
 uptake in combination with available serum and tissue molecular biomarkers.

 -  To compare the results of the secondary imaging objectives with the corresponding CALGB
 50801 results (contingent on reaching agreement with CALGB on the combined analysis of
 the two studies).

 OUTLINE: This is a multicenter study.

 Induction ABVD chemotherapy: Patients receive doxorubicin hydrochloride IV, bleomycin sulfate
 IV, 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 in the absence of disease progression or
 unacceptable toxicity.

 Patients are then assigned to an intervention arm according to fludeoxyglucose F 18 (18 FDG)
 positron emission tomography (PET)/computed tomography (CT) results (negative vs positive).

 -  ABVD (18FDG-PET/CT negative): Patients receive doxorubicin hydrochloride, bleomycin
 sulfate, vinblastine, and dacarbazine as in induction chemotherapy. Treatment repeats
 every 28 days for 4 courses in the absence of disease progression or unacceptable
 toxicity. Within 3-6 weeks after completion of chemotherapy, patients undergo
 involved-node radiotherapy (INRT) 5 days a week for approximately 3½ weeks.

 -  Escalated or standard BEACOPP* (18FDG-PET/CT positive): Patients receive doxorubicin
 hydrochloride IV and cyclophosphamide IV over 60 minutes on day 1, etoposide IV over 60
 minutes on days 1-3, procarbazine hydrochloride orally (PO) on days 1-7, prednisone PO
 on days 1-14, and bleomycin sulfate IV and vincristine sulfate IV on day 8. Treatment
 repeats every 21 days for 4 courses in the absence of disease progression or
 unacceptable toxicity. Within 3-6 weeks after completion of chemotherapy, patients who
 achieve complete response with a negative 18FDG-PET/CT scan undergo INRT 5 days a week
 for approximately 3½ weeks.

 NOTE: *HIV-positive patients whose 18FDG-PET/CT scans are positive after two courses of
 induction ABVD receive 4 courses of standard BEACOPP followed by INRT.

 Patients undergo 18FDG-PET scans at baseline, and within 8-10 days after 2 courses of ABVD
 induction chemotherapy. Patients also undergo 18FDG-PET/CT** scan within 3-8 weeks after
 completion of 4 courses of BEACOPP and 6 courses of ABVD, and 3 months after completion of
 INRT.

 NOTE: **If PET/CT remains positive, then a biopsy may be performed if medically appropriate
 or clinically feasible at the discretion of the treating physician. If biopsy is positive,
 patients will be followed for survival and secondary malignancies or new primaries.

 Patients may undergo blood sample collection for correlative studies.

 After completion of study therapy, patients are followed up every 3 months for 1 year, every
 6 months for 2 years, and then annually for up to 10 years.
Inclusion Criteria:

 -  Histologically proven classical Hodgkin lymphoma subclassified according to the World
 Health Organization (WHO) Classification of Tumors, 4th edition (2008)

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

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

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

 -  Bone marrow biopsy is required

 -  ECOG performance status 0-2

 -  ANC ≥ 1,000/μL

 -  Platelet count ≥ 100,000/μL

 -  Hemoglobin ≥ 10 g/dL

 -  Serum creatinine ≤ 2 mg/dL

 -  Direct bilirubin ≤ 2 mg/dL

 -  AST/ALT ≤ 2 times upper limit of normal

 -  Women of childbearing potential and sexually active males must be strongly advised to
 use an accepted and effective method of contraception

 -  LVEF by ECHO or MUGA normal unless thought to be disease related

 -  DLCO ≥ 60% with no symptomatic pulmonary disease unless thought to be disease related

 -  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, and
 an HIV test is required for entry on this protocol

 -  HIV-positive patients are eligible if they have CD4 counts ≥ 400/mm³ and are on
 concurrent antiretrovirals

 -  Patient HIV status must be known prior to registration

 -  HIV-positive patients must not have multi-drug resistant HIV infections; CD4
 counts < 400/mm³; or other concurrent AIDS-defining conditions

 -  Concurrent antiretroviral therapy for HIV-positive patients (CD4 counts ≥ 400/mm³)
 allowed

 Exclusion Criteria:

 -  Nodular lymphocyte-predominant Hodgkin lymphoma

 -  Pregnant or nursing

 -  "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

 -  Prior treatment (chemotherapy or radiation therapy) for Hodgkin lymphoma