FIL Study on ABVD DD-DI As Upfront Therapy in HL.

Inclusion Criteria:

• Histologically confirmed classical HL

• Previously untreated disease

• Age 18-60 years

• Ann Arbor stage IIB with extranodal involvement and/or mediastinal bulk, III and IV (Appendix A)

• At least one target PET-avid bidimensionally assessable lesion

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2 (Appendix B)

• Adequate organ and marrow function as defined below: absolute neutrophil count >1,0x109/L, platelets >75 x109/L

• Total bilirubin <2 mg/dl without a pattern consistent with Gilbert's syndrome

• Aspartate Transaminase and Alanine Transaminase (AST/ALT) <3 X institutional UpperLimits of Normality (ULN)

• Creatinine within normal institutional limits or creatinine clearance >50mL/min/1.72 m2 (Appendix C)

• Females of childbearing must have a negative pregnancy test at medical supervisioneven if had been using effective contraception

• Life expectancy > 6 months

• Able to adhere to the study visit schedule and other protocol requirements

• Sign (or their legally acceptable representatives must sign) an informed consentdocument indicating that they understand the purpose of and procedures required forthe study and are willing to participate in the study.

• Access to PET-CT scans facilities qualified by FIL

Exclusion Criteria:

• Nodular Lymphocyte Predominant HL

• Ann Arbor stage IIB without extranodal involvement and/or mediastinal bulky

• Prior chemotherapy or radiation therapy

• Pregnant or lactating females

• Known hypertension (as defined by the updated Guidelines [76]), cardiac arrhythmia,conduction abnormalities, ischemic cardiopathy, left ventricular hypertrophy or leftventricular ejection fraction (LVEF) ≤50% at echocardiography.

• Abnormal QTc interval prolonged (>450 msec in males; >470 msec in women)

• Diffusion lung capacity for CO (DLCO) and/or forced expiratory volume in the 1stsecond (FEV1) tests <50% of predicted not related to impaired respiratory capacitydue to airway compression by mediastinal masses or parenchymal lymphoma

• Known cerebral or meningeal disease (HL or any other etiology)

• Prior history of malignancies unless the patient has been free of the disease forfive years. Exceptions include the following: basal cells carcinoma of the skin,squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma insitu of the breast and prostate cancer with TNM stage of T1a or T1b

• Uncontrolled infectious disease

• Human immunodeficiency virus (HIV) positivity or active infectious A, B or Chepatitis. HBsAg-negative patients with anti-HBc antibody and can be enrolledprovided that Hepatitis B Virus (HBV)-DNA are negative and that antiviral treatmentwith nucleos(t)ide analogs is provided

• Uncompensated diabetes

• Refusal of adequate contraception

• Any medical or psychiatric illness that could, in the investigator's opinion,potentially interfere with the completion of treatment.