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

Phase 1

• Conditions: Advanced stage Hodgkin Lymphoma; MedDRA version: 20.1 Level: LLT Classification code 10080208 Term: Classical Hodgkin lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: PT Classification code 10020206 Term: Hodgkin's disease System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: HLT Classification code 10020243 Term: Hodgkin's disease NEC System Organ Class: 10005329 - Blood and lymphatic system disorders; MedDRA version: 20.0 Level: HLGT Classification code 10025319 Term: Lymphomas Hodgkin's disease System Organ Class: 10005329 - Blood and lymphatic system disorders; MedDRA version: 20.0 Level: SOC Classification code 10005329 Term: Blood and lymphatic system disorders System Organ Class: 10005329 - Blood and lymphatic system disorders; MedDRA version: 20.0 Level: SOC Classification code 10029104 Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps) System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-000498-35-BE
• Lead Sponsor: European Organisation for Research and Treatment of Cancer (EORTC)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-11-21
• Last Update Posted: 30 April 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 150

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) (GHSG)
- Stage III - IV
• Participation in translational research is mandatory and therefore patient must consent for it. The following material must be available:
- Archival tumor tissue available (15 blank formalin fixed paraffin embedded tissue samples mounted on APES slides or a tissue block);
- To allow sequential sampling of blood during the course of the trial.
• 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.
• 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 150
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 5.0
• Any of the following cardiovascular conditions or values:
- within 6 months before registration:
• A left-ventricular ejection fraction <50%
• New York Heart Association (NYHA) Class III or IV heart failure (see Appendix D).
• 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:
• Myocardial infarction
• Patients with poorly controlled diabetes mellitus (HbA1c > 7.5 % 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)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified