Hodgkin Lymphoma
Conditions
Keywords
HL
Brief summary
This study aims to evaluate the efficacy of brentuximab vedotin + AVD combination (doxorubicine, vinblastine, dacarbazine) in patients with Hodgkin lymphoma stage I / II with an unfavorable diagnosis, assessed by the negativity of PET (positron emission tomography ) after two cycles of chemotherapy.
Detailed description
Patients will receive either ABVD chemotherapy (standard treatment = doxorubicin, bleomycin, vinblastine, dacarbazine) or the Brentuximab vedotin in combination with chemotherapy AVD (study treatment), depending on randomization. Radiotherapy is planned after chemotherapy or immunochemotherapy. PET scans will be performed before inclusion, after 2 cycles of chemotherapy and after 4 cycles of chemotherapy (if PET after two cycles was positive), at the end of treatment and during follow-up period.
Interventions
DRUGDoxorubicin
25mg/m2
DRUGBleomycin
10mg/m2
DRUGVinblastine
6mg/m2
DRUGDacarbazine
375mg/m2
DRUGBrentuximab Vedotin
1.2 mg/kg
Sponsors
Millennium Pharmaceuticals, Inc.
The Lymphoma Academic Research Organisation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed CD30+ classical Hodgkin lymphoma * 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, including patients with at least one of the following factors: * CSII ≥ 4 nodal areas * age ≥ 50 yrs * M/T ratio ≥ 0.35 * 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 * Availability for periodic blood sampling, study-related assessments, and management of toxicity at the treating institution. * Female patients who: * Are postmenopausal for at least 1 year before the screening visit, OR are surgically sterile, OR * If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, 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. * Written informed consent. * Required baseline laboratory data: * Absolute neutrophil count ≥ 1,500/µL * Platelet count ≥ 75,000/ µL * Hemoglobin ≥ 8g/dL * Serum total bilirubin ≤ 1.5 X ULN unless the elevation is known to be due to Gilbert syndrome. * Serum creatinine ≤ 2.0 mg/dL and/or calculated creatinine clearance \> 40 mL/minute (Cockcroft-Gault formula or MDRD) * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 X ULN
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 * Myocardial infarction within 2 years of randomization * New York Heart Association (NYHA) Class III or IV heart failure (see Appendix 14) * 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 * 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: * HBsAg positive * HBsAg negative, anti-HBs positive and/or anti-HBc positive and detectable viral DNA (HBsAg negative patients and viral DNA negative and patients 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 not excluded if complete resection. * Dementia or altered mental status * Pregnancy or breastfeeding. * Previous treatment with any anti-CD30 antibody. * Known hypersensitivity to any excipients contained in the BV formulation or known contra-indication to any drug contained in the chemotherapy regimens * Treatment with corticosteroids before baseline PET scan * 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 BV * Treatment with any investigational drug within 30 days before first cycle of treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PET2 assessment | 8 weeks | Assessment of PET after two cycles according to the five-point scale Deauville criteria (Negative = 1, 2, 3 and Positive = 4, 5), based on central review. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete response (CR) rate | 16 weeks | according to Cheson 2007 criteria |
| Progression free survival (PFS) | 5 years | Survival without disease progression |
| Overall survival (OS) | 5 years | — |
Countries
Belgium, Croatia, Denmark, France, Netherlands
Outcome results
None listed