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

• Progression-free survival at 36 months from enrollment [ Designated as safety issue: No ]
  

• Complete response rate [ Designated as safety issue: No ]
  
• Standard uptake values (SUVs) for target sites measured at baseline, after course 2, and after completion of therapy [ Designated as safety issue: No ]
  
• Determination of the optimal cutoff for absolute decrease in maximum SUV body weight (SUVbw) and SUV lean body mass (SUVlbm), relative uptake in tumor vs various reference anatomic sites, IHP criteria as well as various cutoffs for post-therapy maxim ... [ Designated as safety issue: No ]
  
• Volumetric vs 2-dimensional (2-D) measurement changes for target lesions between baseline and after course 2, at the end of chemotherapy, and after IFRT [ Designated as safety issue: No ]
  
• Comparison of qualitative and semiquantitative fludeoxyglucose-PET findings/changes, 2-D and volumetric CT changes, and combinatorial analyses (PET + dedicated CT data) with molecular parameters and conventional parameters [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• To determine the progression-free survival (PFS) at 36 months from enrollment of patients with bulky stage I or II Hodgkin lymphoma treated with ABVD alone or followed by escalated BEACOPP and involved-field radiation therapy.

Secondary

• To evaluate the complete response rate in patients diagnosed with bulky stage I and II Hodgkin lymphoma following PET-response-adapted chemotherapy with or without radiotherapy.
• To determine the predictive value of semiquantitative evaluation of fludeoxyglucose (FDG) uptake using various semiquantitative approaches at baseline, after 2 courses of ABVD, and after completion of therapy.
• To determine the predictive value of volumetric vs 2-dimensional (2-D) measurement changes on CT scan between baseline and after 2 courses, at the end of chemotherapy (PET negative patients only), and after radiotherapy (PET positive patients only), and compare with PET parameters.
• To determine if changes in both qualitative and semiquantitative FDG-PET findings/changes between baseline and after course 2, at the end of chemotherapy (PET negative patients only), and after radiotherapy (PET positive patients only) with combination analyses incorporating changes obtained from dedicated CT scans, correlates with response and PFS.
• 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 International 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 elevation of serial serum sCD30, IL10, CCL17, or CCL22 correlate with relapse/progression or PET scan results.
• To confirm independently useful tissue biomarkers (bcl-2, MAL, FOXP3, GzB) for risk stratification in patients with bulky stage I or II Hodgkin lymphoma treated with this regimen.

OUTLINE: This is a multicenter study.

• ABVD chemotherapy: All patients receive doxorubicin hydrochloride IV over 3-5 minutes, 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 then undergo a PET/CT scan and CT scan of the neck (if it was positive at baseline), chest, abdomen, and pelvis. Patients who are PET-positive proceed to escalated BEACOPP chemotherapy. Patients who are PET-negative receive 4 additional courses of ABVD chemotherapy in the absence of disease progression or unacceptable toxicity.
• Escalated BEACOPP chemotherapy: Patients receive doxorubicin hydrochloride IV over 3-5 minutes and cyclophosphamide IV over 60 minutes on day 1; etoposide IV over 60 minutes on days 1, 2, and 3; oral procarbazine hydrochloride once daily on days 1-7; oral prednisone 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. Patients undergo another PET/CT scan and CT scan of the neck (if it was positive at baseline), chest, abdomen, and pelvis. Patients then undergo involved-field radiation therapy 5 days per week for 3½ weeks (for a total of 30.6 Gy).

Within 3-8 weeks after completion of chemotherapy, patients undergo an additional PET/CT scan (utilizing fludeoxyglucose F 18) and CT scan of the neck (if it was positive at baseline), chest, abdomen, and pelvis. Patients who are PET-negative proceed to follow up. Patients who are PET-positive undergo a 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 a biopsy is neither clinically appropriate nor medically feasible proceed to follow up. Patients who defer the biopsy undergo scanning 3 months later and then undergo biopsy as above.

Blood and serum samples may be collected periodically for biomarker and IHC analysis.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 2 years, and then annually for 7 years.