Clinical trial NCT02298283: Brentuximab Vedotin as Consolidation Treatment in Patients With Stage I/II HL and PET Positivity After 2 Cycles of ABVD
Official title: Brentuximab Vedotin as Consolidation Treatment in Patients With Stage I/II Hodgkin's Lymphoma and FDG-PET Positivity After 2 Cycles of ABVD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hodgkin Lymphoma
Keywords: Hodgkin lymphoma
HL
brentuximab vedotin
Lead sponsor: The Lymphoma Academic Research Organisation
Sponsor class: OTHER
First posted: 2014-11-21
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: Inclusion Criteria:

1. Patients must have histologically confirmed cluster of differentiation antigen 30+ (CD30+) classical Hodgkin lymphoma
2. Patients must have provided voluntary written informed consent
3. Supradiaphragmatic Ann Arbor clinical stage I or II
4. Mandatory PET scan performed at diagnosis
5. Patients treated with first-line ABVD and PET scan positive after 2 cycles (Deauville score 4 \& 5)
6. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
7. Life expectancy \> 6 months
8. Patients must be 18-65 years of age
9. Patients must be available for periodic blood sampling, study-related assessments and management of toxicity at the treating institution
10. 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
11. 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
12. 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
13. Patient affiliated to social security system

Exclusion Criteria:

1. Patients with dementia or altered mental status that would preclude compliance with drug delivery
2. Women who are pregnant or breastfeeding
3. Patients with symptomatic pulmonary disease
4. 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%
5. 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
6. 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
7. 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
8. Known Human Immunodeficiency Virus (HIV), known or suspected hepatitis C Virus (HCV) or human T-cell lymphotrophic virus (HTLV) serology positivity
9. Patients who have been treated previously with any anti-CD30 antibody
10. Known hypersensitivity to any excipients contained in the brentuximab vedotin formulation
11. Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of Progressive Multifocal Leukoencephalopathy (PML)
12. Any sensory or motor peripheral neuropathy greater than or equal to Grade 2
13. 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

Primary outcomes:
measure: Progression free survival (PFS)
timeFrame: 2 years
Secondary outcomes:
measure: Complete Response rate (CR rate)
timeFrame: 35 weeks
measure: Overall survival
timeFrame: 4 years
Other outcomes:
Locations:
city: Argenteuil
country: France
facility: CH Victor Dupouy
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord
city: Caen
country: France
facility: Centre François Baclesse
city: Chambéry
country: France
facility: CH de Chambéry
city: Corbeil-Essonnes
country: France
facility: CH Sud Francilien
city: Creteil
country: France
facility: Hôpital Henri Mondor
city: Dijon
country: France
facility: CHU de Dijon - Hôpital le Bocage
city: Le Chesnay
country: France
facility: Hôpital André Mignot
city: Le Mans
country: France
facility: Clinique Victor Hugo
city: Lille
country: France
facility: CHRU Lille - Hôpital Claude Huriez
city: Limoges
country: France
facility: CHU de Limoges
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Institut Paoli Calmette
city: Marseille
country: France
facility: Hôpital de la Conception
city: Montpellier
country: France
facility: CHU Montpellier - Saint ELOI
city: Nantes
country: France
facility: CHU de Nantes
city: Paris cedex 10
country: France
facility: Hôpital Saint Louis
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: Hôpital de la Pitié Salpétrière
city: Perpignan
country: France
facility: CH Perpignan
city: Pessac
country: France
facility: Hôpital Haut Lévêque
city: Pierre Bénite Cedex
country: France
facility: CHU Lyon Sud
city: Reims
country: France
facility: CHU Robert Debre
city: Rennes
country: France
facility: CHU Pontchaillou
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Strasbourg
country: France
facility: CHU de Strasbourg
city: Toulouse
country: France
facility: I.U.C.T Oncopole
city: Tours
country: France
facility: CHU Bretonneau
city: Vandœuvre-lès-Nancy
country: France
facility: CHU de Brabois
city: Villejuif
country: France
facility: Gustave Roussy Cancer Campus
Study officials:
affiliation: Lymphoma Study Association
name: Pauline BRICE, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Lymphoma Study Association
name: Thomas GASTINNE, MD
role: PRINCIPAL_INVESTIGATOR
References: