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

• Progression-free survival (PFS) at 36 months [ Designated as safety issue: No ]
• PFS after 2 courses of ABVD [ Designated as safety issue: No ]

• Complete response rate [ Designated as safety issue: No ]
• FDG/PET uptake [ Designated as safety issue: No ]
• Volumetric changes on CT scan after courses 2 and 4 of ABVD [ Designated as safety issue: No ]
• Changes in metabolic parameters [ Designated as safety issue: No ]

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Radiation therapy uses high energy x-rays to kill cancer cells. Giving combination chemotherapy together with radiation therapy may kill more cancer cells and allow doctors to save the part of the body where the cancer started. Comparing results of diagnostic procedures, such as PET scan, 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 trial is studying how well chemotherapy based on PET scan works in treating patients with stage I or stage II Hodgkin lymphoma.

OBJECTIVES:

Primary

• To determine the progression-free survival (PFS) of patients with non-bulky stage I or II Hodgkin lymphoma treated with ABVD alone or followed by escalated BEACOPP and involved-field radiation therapy.
• To compare the PFS of patients who are PET positive versus PET negative after 2 courses of ABVD.

Secondary

• To evaluate the complete response rate in patients treated with these regimens.
• To determine the predictive value of semiquantitative evaluation of FDG/PET uptake using various approaches at baseline, after 2 courses of AVBD, and at completion of therapy.
• To determine the predictive value of volumetric changes on CT scan after courses 2 and 4 of ABVD and compare with PET parameters with and without combination analyses (PET+dedicated CT data).
• To compare the predictive value of metabolic parameters/changes both visual and quantitative, IHP criteria, volumetric CT changes, molecular parameters, and conventional parameters, including initial prognostic score.
• To assess whether elevated baseline serum soluble CD30 (sCD30), IL10, CCL17, and CCL22 correlate with clinical response and PFS.
• To assess whether persistent or recurrent elevated serial serum sCD30, IL10, CCL17, or CCL22 correlate with relapse/progression or PET scan results.
• To confirm independently useful tissue biomarkers for risk stratification in patients with non-bulky stage I and II Hodgkin lymphoma treated with these regimens.
• To compare mediastinal bulk on standing PA and lateral chest x-ray (> 0.33 maximum chest diameter) with chest CT (mass > 10 cm).

OUTLINE: This is a multicenter study.

• ABVD chemotherapy: Patients receive doxorubicin hydrochloride 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, oral procarbazine on days 1-7, oral prednisone 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.

Patients may undergo blood sample collection for biomarker studies.

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.

• Biological: bleomycin sulfate
• Drug: ABVD regimen
• Drug: BEACOPP regimen
• Drug: cyclophosphamide
• Drug: dacarbazine
• Drug: doxorubicin hydrochloride
• Drug: etoposide
• Drug: prednisone
• Drug: procarbazine hydrochloride
• Drug: vinblastine sulfate
• Drug: vincristine sulfate
• Other: laboratory biomarker analysis
• Procedure: computed tomography
• Radiation: fludeoxyglucose F 18
• Radiation: radiation therapy

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