Brentuximab Vedotin Associated With Chemotherapy in Untreated Patients With Hodgkin Lymphoma.

Hodgkin Lymphoma Clinical Trial

— BREACH  

Official title:

Brentuximab Vedotin Associated With Chemotherapy in Untreated Patients With Stage I/II Unfavourable Hodgkin Lymphoma. A Randomized Phase II LYSA-FIL-EORTC Intergroup Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02292979
• Other study ID #: BREACH
• Status: Completed
• Phase: Phase 2
• Start date: March 2015
• Est. completion date: June 2, 2022

Study information

• Verified date: August 2022
• Source: The Lymphoma Academic Research Organisation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 170
• Est. completion date: June 2, 2022
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Hodgkin Disease
• Hodgkin Lymphoma
• Lymphoma

Intervention

Drug:
• Doxorubicin
25mg/m2
• Bleomycin
10mg/m2
• Vinblastine
6mg/m2
• Dacarbazine
375mg/m2
• Brentuximab Vedotin
1.2 mg/kg

Locations

Country	Name	City	State
Belgium	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	CHU Dinant Godinne	Yvoir
Croatia	University Hospital Rebro	Zagreb
Denmark	Rigshospitalet	Copenhagen
France	CHU d'Amiens	Amiens
France	CHU d'Angers	Angers
France	CH de Annecy	Annecy
France	CHU Jean Minjoz	Besançon
France	CH de Bourg en Bresse	Bourg en Bresse
France	Centre François Baclesse	Caen
France	CHU de Caen	Caen
France	CH de Chalon sur Saône	Chalon sur Saône
France	CH de Chambéry	Chambéry
France	Hôpital Antoine Béclère	Clamart
France	CHU de Clermont-Ferrand	Clermont-Ferrand
France	CH Sud Francilien de Corbeil	Corbeil Essonnes
France	CHU Henri Mondor	Créteil
France	CHU de Dijon	Dijon
France	CHU de Grenoble	Grenoble
France	CH La Rochelle	La Rochelle
France	Centre Hospitalier de Versailles - André Mignot	Le Chesnay
France	CHRU de Lille - Hôpital Claude Hurriez	Lille
France	CHU de Limoges	Limoges
France	Centre Léon Bérard	Lyon
France	Institut Paoli Calmettes	Marseille
France	CH de Meaux	Meaux
France	CHR de Metz	Metz
France	CHU de Montpellier - Saint Eloi	Montpellier
France	CHU de Mulhouse	Mulhouse
France	CHU Nancy Brabois	Nancy
France	CHU Hôtel Dieu Nantes	Nantes
France	CHU de Nîmes	Nîmes
France	Hôpital de la Pitié Salpétrière	Paris
France	Hôpital Necker	Paris
France	Hôpital Saint Antoine	Paris
France	Hôpital Saint Louis	Paris
France	Centre François Magendie	Pessac
France	Centre Hospitalier Lyon Sud	Pierre Bénite
France	CHU Robert Debré	Reims
France	CHU Pontchaillou	Rennes
France	CH de Roubaix	Roubaix
France	Centre Henri Becquerel	Rouen
France	Institut de Cancérologie de Loire	Saint Priest en Jarez
France	CHU de Strasbourg	Strasbourg
France	CHU de Toulouse	Toulouse
France	CHU Bretonneau	Tours
France	Institut Gustave Roussy	Villejuif
Netherlands	Academisch Medisch Centrum - Universiteit van Amsterdam	Amsterdam
Netherlands	Antoni Van Leeuwenhoekziekenhuis	Amsterdam
Netherlands	Amphia Ziekenhuis	Breda
Netherlands	Reinier De Graaf Gasthuis	Delft
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Leiden University Medical Centre	Leiden
Netherlands	Radboud University Medical Center Nijmegen	Nijmegen
Netherlands	Erasmus MC	Rotterdam
Netherlands	Erasmus MC Cancer Institute - location Daniel den Hoed	Rotterdam

Sponsors (2)

Lead Sponsor	Collaborator
The Lymphoma Academic Research Organisation	Millennium Pharmaceuticals, Inc.

Countries where clinical trial is conducted

Belgium,  Croatia,  Denmark,  France,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PET2 assessment	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.	8 weeks
Secondary	Complete response (CR) rate	according to Cheson 2007 criteria	16 weeks
Secondary	Progression free survival (PFS)	Survival without disease progression	5 years
Secondary	Overall survival (OS)		5 years