Advanced Hodgkin Lymphoma Clinical Trial
— COBRAOfficial title:
Very Early PET-response Adapted Targeted Therapy for Advanced Hodgkin Lymphoma: a Single -Arm Phase II Study
| Verified date | November 2023 |
| Source | European Organisation for Research and Treatment of Cancer - EORTC |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Active, not recruiting |
| Enrollment | 150 |
| Est. completion date | November 16, 2026 |
| Est. primary completion date | August 28, 2023 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 60 Years |
| Eligibility | 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) |
| Country | Name | City | State |
|---|---|---|---|
| Belgium | ZNA Stuivenberg | Antwerp | |
| Belgium | Universitair Ziekenhuis Antwerpen | Edegem | |
| Belgium | U.Z. Leuven - Campus Gasthuisberg | Leuven | |
| Denmark | University Hospitals Copenhagen - Rigshospitalet | Copenhagen | |
| Netherlands | Amsterdam UMC - Locatie AMC | Amsterdam | |
| Netherlands | Deventer Ziekenhuis | Deventer | |
| Netherlands | University Medical Center Groningen | Groningen | |
| Netherlands | Medisch Centrum Leeuwarden-Zuid | Leeuwarden | |
| Netherlands | Haaglanden Medisch Centrum (HMC) - Haaglanden MC - locatie Antoniushove | Leidschendam | |
| Netherlands | Radboudumc - Radboud University Medical Center Nijmegen | Nijmegen | |
| Netherlands | Erasmus MC | Rotterdam | |
| Poland | Maria Sklodowska Curie National Institute of Oncology - National Research Institute | Warsaw | |
| Portugal | Instituto Portugues De Oncologia - Francisco Gentil - Centro De Lisboa | Lisboa | |
| Slovakia | National Cancer Institute | Bratislava | |
| Spain | Hospital Duran i Reynals (Institut Catala D'Oncologia) | L'Hospitalet De Llobregat | |
| Spain | Complejo Hospitalario de Navarra | Pamplona |
| Lead Sponsor | Collaborator |
|---|---|
| European Organisation for Research and Treatment of Cancer - EORTC |
Belgium, Denmark, Netherlands, Poland, Portugal, Slovakia, Spain,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Modified Progression-free survival (mPFS) | Modified PFS (mPFS) is defined as the time interval between the date of treatment start and the date of the first of: Progressive disease (PD) Start of new treatment for Classical Hodgkin Lymphoma (cHL) when not in Complete Response at the end of protocol treatment; in this case, the date of mPFS is the date of the FDG-PET/CT scan at the end of protocol treatment. Switching therapy prior to end of protocol treatment for reasons other than Progressive Disease is not considered an event for mPFS. "End of protocol treatment" refers to completion of the planned protocol treatment with no more than 1 missed cycle, including radiotherapy on PET positive lesions if administered Death due to any cause |
4 years after start of first patient in | |
| Secondary | Proportion of patients with a negative FDG-PET | It will be assessed how many patients have a negative FDG-PET image when taken at the end of their first cycle of BrAVD. The BrAVD cycle lasts 4 weeks. | 4 years after start of first patient in | |
| Secondary | Progression-free survival (PFS) | Progression-free survival | 4 years after start of first patient in | |
| Secondary | Overall survival | Overall survival | 4 years after start of first patient in | |
| Secondary | Adverse events graded according to the National Cancer Institute Common Occurrence of Adverse Events | Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for adverse events (NCI-CTCAE) version 5.0 | 4 years after start of first patient in |