Very Early PET-response Adapted Targeted Therapy for Advanced Hodgkin Lymphoma: a Single -Arm Phase II Study

• Status: Recruiting
• Trial end date: 2023-09-01
• Target enrollment: 0
• Participant gender: All

Summary

The main objective of this trial is to assess whether treatment adaptation based on a very early FDG-PET/CT results in improved efficacy while minimizing treatment toxicity in advanced stage Hodgkin Lymphoma (HL) patients treated with brentuximab vedotin (BV)-containing regimens.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Treatments: Antibodies, Monoclonal; Brentuximab Vedotin; Cyclophosphamide; Dacarbazine; Doxorubicin; Etoposide; Etoposide phosphate; Liposomal doxorubicin; Vinblastine

Criteria

Inclusion Criteria:

• Previously untreated, histologically proven classical Hodgkin lymphoma;

• 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)

• Stage III - IV

• Consent to participation in translational research:

• Archival tumor tissue available (15 blank formalin fixed paraffin embedded tissue samples mounted on APES slides or a tissue block).

• 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 adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 6 months after the last dose of treatment. A highly effective method of birth control is defined as a method which results in a low failure rate (i.e. less than 1 percent per year) when used consistently and correctly.

• 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.

• 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.

Exclusion Criteria:

• Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of Progressive Multifocal Leukoencenphalopathy

• Symptomatic neurologic disease compromising normal activities of daily living or requiring medications

• Sensory or motor peripheral neuropathy greater than or equal to grade 2 according to CTCAE version 4.0

• Any of the following cardiovascular conditions or values:

within 6 months before registration:

• A left-ventricular ejection fraction <50 percent (at registration)

• 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 within 2 years before registration

• Myocardial infarction

• Patients with poorly controlled diabetes mellitus (HbA1c > 7.5 percent or a fasting blood sugar > 200 mg/dL).

• Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks prior to registration.

• Known HIV infection, chronic active hepatitis C, HBV positivity (HBsAg + patients; HBsAg -/HBcAb+/HBV DNA+ patients).

Note: HBsAg-/HBV DNA - patients are eligible; patients who are seropositive due to vaccination are eligible

• Concomitant or previous malignancies within the past 5 years with the exception of adequately treated carcinoma in situ of the cervix , nonmelanoma skin cancer.

• Previous treatment with anti CD30 antibodies

• Known hypersensitivity to any excipient contained in Brentuximab Vedotin formulation and other study drugs. Refer to Summary Product Characteristics for list of excipients.

• Concurrent anti-cancer treatment or use of any investigational agent(s)