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

• Status: Active, not recruiting
• Trial end date: 2023-01-01
• Target enrollment: 0
• Participant gender: All

Summary

The FIL-Rouge is a randomized, open-label, multicenter, phase III, 2-arm study. The primary objective is to compare efficacy and tolerability of the intensified variant 'dose-dense/dose-intense ABVD' (ABVD DD-DI) with an interim PET response-adapted ABVD program as upfront therapy in advanced-stage classical Hodgkin Lymphoma (HL).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Fondazione Italiana Linfomi ONLUS
• Treatments: Bleomycin; Dacarbazine; Doxorubicin; Liposomal doxorubicin; Vinblastine

Criteria

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 >1,0 x109/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 Upper Limits of Normality (ULN)

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

• Females of childbearing must have a negative pregnancy test at medical supervision even 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 consent document indicating that they understand the purpose of and procedures required for the 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 left ventricular 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 1st second (FEV1) tests <50% of predicted not related to impaired respiratory capacity due 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 for five years. Exceptions include the following: basal cells carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ 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 C hepatitis. HBsAg-negative patients with anti-HBc antibody and can be enrolled provided that Hepatitis B Virus (HBV)-DNA are negative and that antiviral treatment with 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.