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

NCT ID: NCT02292979

Last Updated: 2022-08-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 170 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-31
• Study Completion Date: 2022-06-02

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.

Conditions

Hodgkin Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ABVD

Patients in standard arm receive Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine on Day 1 and D14 of each 4-week-cycle during 4 cycles

Group Type: ACTIVE_COMPARATOR

Doxorubicin

Intervention Type: DRUG

25mg/m2

Bleomycin

Intervention Type: DRUG

10mg/m2

Vinblastine

Intervention Type: DRUG

6mg/m2

Dacarbazine

Intervention Type: DRUG

375mg/m2

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

Group Type: EXPERIMENTAL

Doxorubicin

Intervention Type: DRUG

25mg/m2

Vinblastine

Intervention Type: DRUG

6mg/m2

Dacarbazine

Intervention Type: DRUG

375mg/m2

Brentuximab Vedotin

Intervention Type: DRUG

1.2 mg/kg

Interventions

Doxorubicin

25mg/m2

Intervention Type: DRUG

Bleomycin

10mg/m2

Intervention Type: DRUG

Vinblastine

6mg/m2

Intervention Type: DRUG

Dacarbazine

375mg/m2

Intervention Type: DRUG

Brentuximab Vedotin

1.2 mg/kg

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

The Lymphoma Academic Research Organisation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marc André, Pr

Role: PRINCIPAL_INVESTIGATOR

Lymphoma Study Association

Luc Fornecker, Dr

Role: PRINCIPAL_INVESTIGATOR

Lymphoma Study Association

Locations

ZNA Middelheim

Antwerp, , Belgium

ZNA Stuivenberg

Antwerp, , Belgium

A.Z. Sint Jan AV

Bruges, , Belgium

Institut Jules Bordet

Brussels, , Belgium

UCL Louvain Saint Luc

Brussels, , Belgium

Grand Hôpital de Charleroi

Charleroi, , Belgium

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

U.Z. Leuven - Campus Gasthuisberg

Leuven, , Belgium

CHU de Liege

Liège, , Belgium

AZ Delta - Campus H. Hartziekenhuis

Roeselare, , Belgium

CHU Dinant Godinne

Yvoir, , Belgium

University Hospital Rebro

Zagreb, , Croatia

Rigshospitalet

Copenhagen, , Denmark

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 Necker

Paris, , France

Hôpital de la Pitié Salpétrière

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, , France

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 Cancer Institute - location Daniel den Hoed

Rotterdam, , Netherlands

Erasmus MC

Rotterdam, , Netherlands

Countries

Belgium; Croatia; Denmark; France; Netherlands

References

Goldkuhle M, Kreuzberger N, von Tresckow B, Eichenauer DA, Specht L, Monsef I, Skoetz N. Chemotherapy alone versus chemotherapy plus radiotherapy for adults with early-stage Hodgkin's lymphoma. Cochrane Database Syst Rev. 2024 Dec 2;12(12):CD007110. doi: 10.1002/14651858.CD007110.pub4.

Reference Type: DERIVED

PMID: 39620432 (View on PubMed)

Fornecker LM, Lazarovici J, Aurer I, Casasnovas RO, Gac AC, Bonnet C, Bouabdallah K, Feugier P, Specht L, Molina L, Touati M, Borel C, Stamatoullas A, Nicolas-Virelizier E, Pascal L, Lugtenburg P, Di Renzo N, Vander Borght T, Traverse-Glehen A, Dartigues P, Hutchings M, Versari A, Meignan M, Federico M, Andre M; LYSA-FIL-EORTC Intergroup. Brentuximab Vedotin Plus AVD for First-Line Treatment of Early-Stage Unfavorable Hodgkin Lymphoma (BREACH): A Multicenter, Open-Label, Randomized, Phase II Trial. J Clin Oncol. 2023 Jan 10;41(2):327-335. doi: 10.1200/JCO.21.01281. Epub 2022 Jul 22.

Reference Type: DERIVED

PMID: 35867960 (View on PubMed)

Other Identifiers

BREACH

Identifier Type: -

Identifier Source: org_study_id