Untreated patients with histologically confirmed CD30+ classical Hodgkin lymphoma (stage I/II), aged > or = 18 and < or = 60 years old, with at least one unfavourable clinical pronostic factor MedDRA version: 17.0 Level: LLT Classification code 10020328 Term: Hodgkin's lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 17.0 Level: SOC Classification code 10029104 Term: Neoplasms benign, malignant and unspecified (incl cys
Conditions
Interventions
Product Name: Brentuximab vedotin
Product Code: SGN-35
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: brentuximab vedotin
CAS Number: 914088-09-8
Other desc
Sponsors
LYSARC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Histologically confirmed CD30+ classical Hodgkin lymphoma according to local evaluation • Supradiaphragmatic Ann Arbor clinical stage I or II • Previously untreated • PET scan without IV contrast at diagnosis available for central review with at least one hypermetabolic lesion • Unfavourable (U) characteristics according to the classic EORTC/LYSA clinical prognostic factors. Unfavourable (U) subset includes patients with at least one of the following factors: o CSII = 4 nodal areas o age = 50 yrs o M/T ratio = 0.35 o ESR = 50 (without B-symptoms) or ESR = 30 with B-symptoms • ECOG performance status 0-2 • Life expectancy > 6 months • Age 18 to 60 years (= 18 years to = 60 years) • Patients must be available for periodic blood sampling, study-related assessments, and management of toxicity at the treating institution. • Female patients who: o Are postmenopausal for at least 1 year before the screening visit, OR are surgically sterile, OR o If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 6 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse • Male patients, even if surgically sterilized (ie, status postvasectomy), who: o Agree to practice effective barrier contraception during the entire study treatment period and through 6 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse. • Patients must give written informed consent. A copy of the informed signed consent form will be retained in the patient’s chart. • Required baseline laboratory data: o Absolute neutrophil count = 1,500/µL o Platelet count = 75,000/ µL o Hemoglobin = 8g/dL o Serum total bilirubin = 1.5 X ULN unless the elevation is known to be due to Gilbert syndrome. o Serum creatinine = 2.0 mg/dL and/or calculated creatinine clearance > 40 mL/minute (Cockcroft-Gault formula or MDRD) o Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3 X ULN 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 170 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Histological diagnosis different from classical Hodgkin Lymphoma. Nodular lymphocyte predominant subtypes (nodular paragranuloma or Poppema paragranuloma) are excluded. • Known cerebral or meningeal disease of any etiology, including signs or symptoms of PML • Any sensory or motor peripheral neuropathy = Grade 2 • Known history of any of the following cardiovascular conditions o Myocardial infarction within 2 years of randomization o New York Heart Association (NYHA) Class III or IV heart failure (see Appendix 14) o 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 o Recent evidence (within 30 days before first dose of study drug) of a left-ventricular ejection fraction <50% • Unstable diabetes mellitus (to avoid uninterpretable FDG-PET scan). • Known HIV positive • HCV positive • HBV positive. This means: o HBsAg positive o HBsAg negative, anti-HBs positive and/or anti-HBc positive and detectable viral DNA o Note: ? Patients who are HBsAg negative and viral DNA negative are eligible ? Patients who are seropositive due to a history of hepatitis B vaccine are eligible. • Any history of cancer during the last 5 years, with the exception of non-melanoma skin tumors. Carcinoma in situ of any type are not excluded if they have undergone complete resection. • Dementia or altered mental status that would preclude compliance with drug delivery • Pregnancy or breastfeeding. Females of childbearing potential having a positive ß-HCG pregnancy test result during screening or a positive pregnancy test (urinary or blood) within 1 day before start of treatment. • Previous treatment with any anti-CD30 antibody. • Known hypersensitivity to any excipients contained in the brentuximab vedotin formulation or known contra-indication to any drug contained in the chemotherapy regimens (for ex.: pulmonary or neurological disease grade = 2) • Treatment with corticosteroids before baseline PET scan (PET 0) • Patients with known active viral, bacterial, or fungal infection requiring treatment with antimicrobial therapy or with untreated known active Grade 3 viral, bacterial, or fungal infection, within 2 weeks prior to the first dose of brentuximab vedotin • Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy or immune-chemotherapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of the combination AVD+brentuximab vedotin in untreated patients with stage I/II unfavourable Hodgkin lymphoma, as measured by the rate of PET negativity after two cycles of immuno chemotherapy, PET assessment based on central review.;Secondary Objective: To assess the efficacy and safety of AVD+brentuximab vedotin as measured by: • Secondary efficacy endpoints: - CR rate (according to Cheson 2007) at the end of treatment - Progression-free survival - Overall survival • Secondary safety endpoint: - Toxicity of Brentuximab vedotin in combination with combined modality treatment will be assessed. ;Primary end point(s): The primary endpoint is the PET response rate according to the Deauville criteria based on central review assessed after 2 cycles of chemotherapy or immuno-chemotherapy (ABVD or AVD/Brentuximab vedotin).;Timepoint(s) of evaluation of this end point: The categorization of the patients according to PET results will be performed as follows: - 1, 2 or 3: PET negative = Responder - 4- 5: PET positive =Non-responder. - Missing PET evaluation (for whatever reason) : Non-responder As sensitivity analysis will be performed on the Evaluable Set. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints are the efficacy and the safety;Timepoint(s) of evaluation of this end point: Secondary efficacy endpoints will include: • COMPLETE RESPONSE RATES ACCORDING TO PET RESPONSE AT END OF TREATMENT Disease response evaluation at end of treatment (after radiotherapy) will be used to determine the Response Rate. • PET RESPONSE RATE (ACCORDING TO DEAUVILLE CRITERIA) AT END OF TREATMENT PET evaluation will be performed at end of treatment. • PROGRESSION FREE SURVIVAL (PFS) PFS is defined as the time from randomization into the study to the first observation of documented disease progression or death due to any cause. If a subject has not progressed or died, PFS will be censored at the time of last visit assessment. • OVERALL SURVIVAL (OS) Overall survival will be measured from date of randomization into the study to the date of death from any cause. | — |
Countries
France
Contacts
Public ContactCo-coordinating Investigator
Dr Luc-Matthieu Fornecker
Outcome results
None listed