BREACH: Brentuximab Vedotin Associated With Chemotherapy in Untreated Patients With Hodgkin Lymphoma.
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: ABVD Patients in standard arm receive Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine on Day 1 and D14 of each 4-week-cycle during 4 cycles |
Drug: Doxorubicin
25mg/m2
Drug: Bleomycin
10mg/m2
Drug: Vinblastine
6mg/m2
Drug: Dacarbazine
375mg/m2
|
| Experimental: AVD+BV Patients in experimental arm receive Doxorubicin, Vinblastine, Dacarbazine and Brentuximab vedotin on Day 1 and D14 of each 4-week-cycle during 4 cycles |
Drug: Doxorubicin
25mg/m2
Drug: Vinblastine
6mg/m2
Drug: Dacarbazine
375mg/m2
Drug: Brentuximab Vedotin
1.2 mg/kg
|
Outcome Measures
Primary Outcome Measures
- 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
- 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]
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | ZNA Middelheim | Antwerpen | Belgium | ||
| 2 | ZNA Stuivenberg | Antwerpen | Belgium | ||
| 3 | A.Z. Sint Jan AV | Brugge | Belgium | ||
| 4 | Institut Jules Bordet | Bruxelles | Belgium | ||
| 5 | UCL Louvain Saint Luc | Bruxelles | Belgium | ||
| 6 | Grand Hôpital de Charleroi | Charleroi | Belgium | ||
| 7 | Universitair Ziekenhuis Antwerpen | Edegem | Belgium | ||
| 8 | U.Z. Leuven - Campus Gasthuisberg | Leuven | Belgium | ||
| 9 | CHU de Liege | Liege | Belgium | ||
| 10 | AZ Delta - Campus H. Hartziekenhuis | Roeselare | Belgium | ||
| 11 | CHU Dinant Godinne | Yvoir | Belgium | ||
| 12 | University Hospital Rebro | Zagreb | Croatia | ||
| 13 | Rigshospitalet | Copenhagen | Denmark | ||
| 14 | CHU d'Amiens | Amiens | France | ||
| 15 | CHU d'Angers | Angers | France | ||
| 16 | CH de Annecy | Annecy | France | ||
| 17 | CHU Jean Minjoz | Besançon | France | ||
| 18 | CH de Bourg en Bresse | Bourg en Bresse | France | ||
| 19 | Centre François Baclesse | Caen | France | ||
| 20 | CHU de Caen | Caen | France | ||
| 21 | CH de Chalon sur Saône | Chalon sur Saône | France | ||
| 22 | CH de Chambéry | Chambéry | France | ||
| 23 | Hôpital Antoine Béclère | Clamart | France | ||
| 24 | CHU de Clermont-Ferrand | Clermont-Ferrand | France | ||
| 25 | CH Sud Francilien de Corbeil | Corbeil Essonnes | France | ||
| 26 | CHU Henri Mondor | Créteil | France | ||
| 27 | CHU de Dijon | Dijon | France | ||
| 28 | CHU de Grenoble | Grenoble | France | ||
| 29 | CH La Rochelle | La Rochelle | France | ||
| 30 | Centre Hospitalier de Versailles - André Mignot | Le Chesnay | France | 78157 | |
| 31 | CHRU de Lille - Hôpital Claude Hurriez | Lille | France | 59037 | |
| 32 | CHU de Limoges | Limoges | France | ||
| 33 | Centre Léon Bérard | Lyon | France | ||
| 34 | Institut Paoli Calmettes | Marseille | France | ||
| 35 | CH de Meaux | Meaux | France | ||
| 36 | CHR de Metz | Metz | France | ||
| 37 | CHU de Montpellier - Saint Eloi | Montpellier | France | ||
| 38 | CHU de Mulhouse | Mulhouse | France | ||
| 39 | CHU Nancy Brabois | Nancy | France | ||
| 40 | CHU Hôtel Dieu Nantes | Nantes | France | ||
| 41 | CHU de Nîmes | Nîmes | France | ||
| 42 | Hôpital Necker | Paris | France | 75743 | |
| 43 | Hôpital de la Pitié Salpétrière | Paris | France | ||
| 44 | Hôpital Saint Antoine | Paris | France | ||
| 45 | Hôpital Saint Louis | Paris | France | ||
| 46 | Centre François Magendie | Pessac | France | ||
| 47 | Centre Hospitalier Lyon Sud | Pierre Bénite | France | 69495 | |
| 48 | CHU Robert Debré | Reims | France | ||
| 49 | CHU Pontchaillou | Rennes | France | ||
| 50 | CH de Roubaix | Roubaix | France | ||
| 51 | Centre Henri Becquerel | Rouen | France | ||
| 52 | Institut de Cancérologie de Loire | Saint Priest en Jarez | France | ||
| 53 | CHU de Strasbourg | Strasbourg | France | ||
| 54 | CHU de Toulouse | Toulouse | France | ||
| 55 | CHU Bretonneau | Tours | France | 37044 | |
| 56 | Institut Gustave Roussy | Villejuif | France | ||
| 57 | Academisch Medisch Centrum - Universiteit van Amsterdam | Amsterdam | Netherlands | ||
| 58 | Antoni Van Leeuwenhoekziekenhuis | Amsterdam | Netherlands | ||
| 59 | Amphia Ziekenhuis | Breda | Netherlands | ||
| 60 | Reinier De Graaf Gasthuis | Delft | Netherlands | ||
| 61 | University Medical Center Groningen | Groningen | Netherlands | ||
| 62 | Leiden University Medical Centre | Leiden | Netherlands | ||
| 63 | Radboud University Medical Center Nijmegen | Nijmegen | Netherlands | ||
| 64 | Erasmus MC Cancer Institute - location Daniel den Hoed | Rotterdam | Netherlands | ||
| 65 | Erasmus MC | Rotterdam | Netherlands |
Sponsors and Collaborators
- The Lymphoma Academic Research Organisation
- Millennium Pharmaceuticals, Inc.
Investigators
- Principal Investigator: Marc André, Pr, Lymphoma Study Association
- Principal Investigator: Luc Fornecker, Dr, Lymphoma Study Association
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BREACH