Brentuximab Vedotin Associated With Chemotherapy in Untreated Patients With Hodgkin Lymphoma.
- Conditions
- Hodgkin Lymphoma
- Interventions
- Registration Number
- NCT02292979
- Lead Sponsor
- The Lymphoma Academic Research Organisation
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 170
-
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
-
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ABVD Doxorubicin Patients in standard arm receive Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine on Day 1 and D14 of each 4-week-cycle during 4 cycles ABVD Bleomycin Patients in standard arm receive Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine on Day 1 and D14 of each 4-week-cycle during 4 cycles ABVD Vinblastine Patients in standard arm receive Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine on Day 1 and D14 of each 4-week-cycle during 4 cycles ABVD Dacarbazine Patients in standard arm receive Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine on Day 1 and D14 of each 4-week-cycle during 4 cycles AVD+BV Doxorubicin Patients in experimental arm receive Doxorubicin, Vinblastine, Dacarbazine and Brentuximab vedotin on Day 1 and D14 of each 4-week-cycle during 4 cycles AVD+BV Vinblastine Patients in experimental arm receive Doxorubicin, Vinblastine, Dacarbazine and Brentuximab vedotin on Day 1 and D14 of each 4-week-cycle during 4 cycles AVD+BV Dacarbazine Patients in experimental arm receive Doxorubicin, Vinblastine, Dacarbazine and Brentuximab vedotin on Day 1 and D14 of each 4-week-cycle during 4 cycles AVD+BV Brentuximab Vedotin Patients in experimental arm receive Doxorubicin, Vinblastine, Dacarbazine and Brentuximab vedotin on Day 1 and D14 of each 4-week-cycle during 4 cycles
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
Trial Locations
- Locations (65)
ZNA Middelheim
🇧🇪Antwerpen, Belgium
ZNA Stuivenberg
🇧🇪Antwerpen, Belgium
A.Z. Sint Jan AV
🇧🇪Brugge, Belgium
Institut Jules Bordet
🇧🇪Bruxelles, Belgium
UCL Louvain Saint Luc
🇧🇪Bruxelles, Belgium
Grand Hôpital de Charleroi
🇧🇪Charleroi, Belgium
Universitair Ziekenhuis Antwerpen
🇧🇪Edegem, Belgium
U.Z. Leuven - Campus Gasthuisberg
🇧🇪Leuven, Belgium
CHU de Liege
🇧🇪Liege, Belgium
AZ Delta - Campus H. Hartziekenhuis
🇧🇪Roeselare, Belgium
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