Brentuximab Vedotin as Consolidation Treatment in Patients With Stage I/II HL and PET Positivity After 2 Cycles of ABVD
- Conditions
- Hodgkin Lymphoma
- Interventions
- Registration Number
- NCT02298283
- Lead Sponsor
- The Lymphoma Academic Research Organisation
- Brief Summary
This study aims to evaluate the efficacy brentuximab vedotin as consolidation treatment in patients with stage I/II Hodgkin's lymphoma and 18-fluorodeoxyglucose (FDG) -PET positivity after 2 cycles of ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine).
- Detailed Description
This study aims to evaluate the progression free survival after treatment for patient with stage I/II supradiaphragmatic HL patient and PET positive after 2 courses of ABVD.
The treatment consist of 3 phases :
* induction treatment with 2 cycles every 3 weeks of bleomycin, etoposide, Adriamycin, cyclophosphamide, oncovin, procarbazine, and prednisone (BEACOPP) escalated
* radiotherapy 30 Gy starting 3 to 4 weeks after last day of second course of BEACOPP-escalated
* consolidation treatment with 8 cycles every 21 days of brentuximab vedotin
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
-
Patients must have histologically confirmed cluster of differentiation antigen 30+ (CD30+) classical Hodgkin lymphoma
-
Patients must have provided voluntary written informed consent
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Supradiaphragmatic Ann Arbor clinical stage I or II
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Mandatory PET scan performed at diagnosis
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Patients treated with first-line ABVD and PET scan positive after 2 cycles (Deauville score 4 & 5)
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Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
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Life expectancy > 6 months
-
Patients must be 18-65 years of age
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Patients must be available for periodic blood sampling, study-related assessments and management of toxicity at the treating institution
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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
-
Male patients, even if surgically sterilized, who 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
-
Clinical laboratory values as specified below before the first dose of study drug:
- Absolute neutrophil count ≥ 1,500/µL
- Platelet count ≥ 75,000/ µL
- Total bilirubin must be < 1.5 x the upper limit of the normal (ULN) unless the elevation is known to be due to Gilbert syndrome
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST)must be < 3 x the upper limit of the normal range
- Serum creatinine must be < 2.0 mg/dL and/or creatinine clearance or calculated creatinine clearance > 40 mL/minute
- Hemoglobin must be ≥ 8g/dL
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Patient affiliated to social security system
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Patients with dementia or altered mental status that would preclude compliance with drug delivery
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Women who are pregnant or breastfeeding
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Patients with symptomatic pulmonary disease
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Patients with known history of any of the following cardiovascular conditions:
- Myocardial infarction within 2 years of inclusion
- 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
- Recent evidence (within 6 months before first dose of study drug) of a left-ventricular ejection fraction <50%
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Any history of cancer or cancer treatment during the last 3 years with the exception of non-melanoma skin cancer or stage 0 (in situ) carcinoma of any type if they have undergone complete resection
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Uncontrolled infectious disease, including active Hepatitis B Virus (HBV) infection defined by either detection of Hepatitis B surface (HBs) Antigen or presence of Hepatitis B core (HBc) antibody without detectable anti HBs antibody
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Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics at the time of inclusion and planned to be still on going within 2 weeks prior to first study drug dose
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Known Human Immunodeficiency Virus (HIV), known or suspected hepatitis C Virus (HCV) or human T-cell lymphotrophic virus (HTLV) serology positivity
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Patients who have been treated previously with any anti-CD30 antibody
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Known hypersensitivity to any excipients contained in the brentuximab vedotin formulation
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Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of Progressive Multifocal Leukoencephalopathy (PML)
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Any sensory or motor peripheral neuropathy greater than or equal to Grade 2
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Patients that have not completed any prior treatment chemotherapy and/or other investigational agents within at least 5 half-lives of last dose of that prior treatment
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description study treatment 30 Grays * induction = BEACOPP-escalated (bleomycin, etoposide, adriamycin, cyclophosphamide, oncovin, procarbazine, and prednisone) : 2 cycles every 3 weeks * radiotherapy = involved field radiotherapy (IFRT) will be given 3 to 4 weeks after the last day of second BEACOPP at 30 Grays (+boost 6 Grays to area with residual lesion) in 3 weeks * Consolidation = brentuximab vedotin treatment will start 4 weeks after the last day of IFRT and up to 6 weeks. The dose of study treatment is 1.8 mg/kg study treatment brentuximab vedotin * induction = BEACOPP-escalated (bleomycin, etoposide, adriamycin, cyclophosphamide, oncovin, procarbazine, and prednisone) : 2 cycles every 3 weeks * radiotherapy = involved field radiotherapy (IFRT) will be given 3 to 4 weeks after the last day of second BEACOPP at 30 Grays (+boost 6 Grays to area with residual lesion) in 3 weeks * Consolidation = brentuximab vedotin treatment will start 4 weeks after the last day of IFRT and up to 6 weeks. The dose of study treatment is 1.8 mg/kg study treatment Cyclophosphamide * induction = BEACOPP-escalated (bleomycin, etoposide, adriamycin, cyclophosphamide, oncovin, procarbazine, and prednisone) : 2 cycles every 3 weeks * radiotherapy = involved field radiotherapy (IFRT) will be given 3 to 4 weeks after the last day of second BEACOPP at 30 Grays (+boost 6 Grays to area with residual lesion) in 3 weeks * Consolidation = brentuximab vedotin treatment will start 4 weeks after the last day of IFRT and up to 6 weeks. The dose of study treatment is 1.8 mg/kg study treatment Adriamycin * induction = BEACOPP-escalated (bleomycin, etoposide, adriamycin, cyclophosphamide, oncovin, procarbazine, and prednisone) : 2 cycles every 3 weeks * radiotherapy = involved field radiotherapy (IFRT) will be given 3 to 4 weeks after the last day of second BEACOPP at 30 Grays (+boost 6 Grays to area with residual lesion) in 3 weeks * Consolidation = brentuximab vedotin treatment will start 4 weeks after the last day of IFRT and up to 6 weeks. The dose of study treatment is 1.8 mg/kg study treatment Oncovin * induction = BEACOPP-escalated (bleomycin, etoposide, adriamycin, cyclophosphamide, oncovin, procarbazine, and prednisone) : 2 cycles every 3 weeks * radiotherapy = involved field radiotherapy (IFRT) will be given 3 to 4 weeks after the last day of second BEACOPP at 30 Grays (+boost 6 Grays to area with residual lesion) in 3 weeks * Consolidation = brentuximab vedotin treatment will start 4 weeks after the last day of IFRT and up to 6 weeks. The dose of study treatment is 1.8 mg/kg study treatment Bleomycin * induction = BEACOPP-escalated (bleomycin, etoposide, adriamycin, cyclophosphamide, oncovin, procarbazine, and prednisone) : 2 cycles every 3 weeks * radiotherapy = involved field radiotherapy (IFRT) will be given 3 to 4 weeks after the last day of second BEACOPP at 30 Grays (+boost 6 Grays to area with residual lesion) in 3 weeks * Consolidation = brentuximab vedotin treatment will start 4 weeks after the last day of IFRT and up to 6 weeks. The dose of study treatment is 1.8 mg/kg study treatment Etoposide * induction = BEACOPP-escalated (bleomycin, etoposide, adriamycin, cyclophosphamide, oncovin, procarbazine, and prednisone) : 2 cycles every 3 weeks * radiotherapy = involved field radiotherapy (IFRT) will be given 3 to 4 weeks after the last day of second BEACOPP at 30 Grays (+boost 6 Grays to area with residual lesion) in 3 weeks * Consolidation = brentuximab vedotin treatment will start 4 weeks after the last day of IFRT and up to 6 weeks. The dose of study treatment is 1.8 mg/kg study treatment Prednisone * induction = BEACOPP-escalated (bleomycin, etoposide, adriamycin, cyclophosphamide, oncovin, procarbazine, and prednisone) : 2 cycles every 3 weeks * radiotherapy = involved field radiotherapy (IFRT) will be given 3 to 4 weeks after the last day of second BEACOPP at 30 Grays (+boost 6 Grays to area with residual lesion) in 3 weeks * Consolidation = brentuximab vedotin treatment will start 4 weeks after the last day of IFRT and up to 6 weeks. The dose of study treatment is 1.8 mg/kg study treatment Procarbazine * induction = BEACOPP-escalated (bleomycin, etoposide, adriamycin, cyclophosphamide, oncovin, procarbazine, and prednisone) : 2 cycles every 3 weeks * radiotherapy = involved field radiotherapy (IFRT) will be given 3 to 4 weeks after the last day of second BEACOPP at 30 Grays (+boost 6 Grays to area with residual lesion) in 3 weeks * Consolidation = brentuximab vedotin treatment will start 4 weeks after the last day of IFRT and up to 6 weeks. The dose of study treatment is 1.8 mg/kg study treatment G-CSF * induction = BEACOPP-escalated (bleomycin, etoposide, adriamycin, cyclophosphamide, oncovin, procarbazine, and prednisone) : 2 cycles every 3 weeks * radiotherapy = involved field radiotherapy (IFRT) will be given 3 to 4 weeks after the last day of second BEACOPP at 30 Grays (+boost 6 Grays to area with residual lesion) in 3 weeks * Consolidation = brentuximab vedotin treatment will start 4 weeks after the last day of IFRT and up to 6 weeks. The dose of study treatment is 1.8 mg/kg
- Primary Outcome Measures
Name Time Method Progression free survival (PFS) 2 years PFS is defined as the time from the date of the first cycle of ABVD to the first observation of documented disease progression or death due to any cause.
- Secondary Outcome Measures
Name Time Method Overall survival 4 years Complete Response rate (CR rate) 35 weeks according to Cheson 2007
Trial Locations
- Locations (30)
CH Sud Francilien
🇫🇷Corbeil-Essonnes, France
Hôpital André Mignot
🇫🇷Le Chesnay, France
Centre Léon Bérard
🇫🇷Lyon, France
CH de Chambéry
🇫🇷Chambéry, France
CHU de Dijon - Hôpital le Bocage
🇫🇷Dijon, France
Centre François Baclesse
🇫🇷Caen, France
CHU Montpellier - Saint ELOI
🇫🇷Montpellier, France
Hôpital Henri Mondor
🇫🇷Creteil, France
CHRU Lille - Hôpital Claude Huriez
🇫🇷Lille, France
CHU Pontchaillou
🇫🇷Rennes, France
Hôpital de la Pitié Salpétrière
🇫🇷Paris, France
Institut Paoli Calmette
🇫🇷Marseille, France
Hôpital de la Conception
🇫🇷Marseille, France
CHU de Nantes
🇫🇷Nantes, France
Hôpital Saint Louis
🇫🇷Paris cedex 10, France
CH Perpignan
🇫🇷Perpignan, France
Hôpital Haut Lévêque
🇫🇷Pessac, France
CHU Lyon Sud
🇫🇷Pierre Bénite Cedex, France
Hôpital Cochin
🇫🇷Paris, France
CH Victor Dupouy
🇫🇷Argenteuil, France
Polyclinique Bordeaux Nord
🇫🇷Bordeaux, France
Clinique Victor Hugo
🇫🇷Le Mans, France
CHU de Limoges
🇫🇷Limoges, France
Centre Henri Becquerel
🇫🇷Rouen, France
CHU de Strasbourg
🇫🇷Strasbourg, France
CHU Robert Debre
🇫🇷Reims, France
I.U.C.T Oncopole
🇫🇷Toulouse, France
CHU de Brabois
🇫🇷Vandœuvre-lès-Nancy, France
CHU Bretonneau
🇫🇷Tours, France
Gustave Roussy Cancer Campus
🇫🇷Villejuif, France