EORTC-1537-LYMG: Very early FDG-PET-response adapted targeted therapy for advanced Hodgkin lymphoma: a single-arm phase II study

Prior treatment

• Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks prior to registration
• Previous treatment with anti CD30 antibodies
• Concurrent anti-cancer treatment or use of any investigational agent(s)
• Any of the following cardiovascular conditions or values: - within 6 months before registration

Other illness

• Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of Progressive Multifocal Leukoencenphalopathy
• Myocardial infarction
• Known HIV infection, chronic active hepatitis C, HBV positivity (HBsAg + patients; HBsAg -/HBcAb+/HBV DNA+ patients)
• Concomitant or previous malignancies within the past 5 years with the exception of adequately treated carcinoma in situ of the cervix, nonmelanoma skin cancer
• Known hypersensitivity to any excipient contained in Brentuximab Vedotin formulation and other study drugs
• Symptomatic neurologic disease compromising normal activities of daily living or requiring medications
• New York Heart Association (NYHA) Class III or IV heart failure
• Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
• symptomatic coronary heart disease (stable angina pectoris is allowed)
• severe uncontrolled hypertension defined as blood pressure (BP) >150/100 mmHg despite optimal antihypertensive treatment - within 2 years before registration

Lab values

• Patients with poorly controlled diabetes mellitus (HbA1c > 7.5 % or a fasting blood sugar > 200 mg/dL)
• A left-ventricular ejection fraction <50%

Other

• Sensory or motor peripheral neuropathy greater than or equal to grade 2 according to CTCAE version 5.0

• Previously untreated, histologically proven classical Hodgkin lymphoma
• Absence of any medical, psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
• Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations
• Staged by PET with diagnostic-quality CT (i.v. contrast). - Clinical stages according to Lugano 2014 and based on FDG/PET CT:Stage IIB with large mediastinal mass > 1/3 max transverse diameter thorax and/or extranodal lesion(s) (GHSG) - Stage III - IV
• Participation in translational research is mandatory and therefore patient must consent to additional blood samples at multiple time points in the study. In addition, sufficient tissue must be available (15 blank formalin fixed paraffin embedded tissue samples mounted on APES slides or a tissue block)
• Age ≥18 and ≤60
• WHO performance status 0-2
• Patient demonstrates adequate organ function as defined in the protocol
• Women of child bearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours prior to the first dose of study treatment
• Patients of childbearing / reproductive potential should use two birth control methods, as defined by the investigator, from the time of signing the informed consent form, and throughout the entire study and for 6 months after the last dose of treatment
• Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 6 months after the last study treatment