We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Brentuximab Vedotin Associated With Chemotherapy in Untreated Patients With Hodgkin Lymphoma. (BREACH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02292979
Recruitment Status : Completed
First Posted : November 18, 2014
Last Update Posted : August 19, 2022
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
The Lymphoma Academic Research Organisation

Tracking Information
First Submitted Date  ICMJE October 28, 2014
First Posted Date  ICMJE November 18, 2014
Last Update Posted Date August 19, 2022
Actual Study Start Date  ICMJE March 2015
Actual Primary Completion Date December 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 13, 2014)
PET2 assessment [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 13, 2014)
  • Complete response (CR) rate [ Time Frame: 16 weeks ]
    according to Cheson 2007 criteria
  • Progression free survival (PFS) [ Time Frame: 5 years ]
    Survival without disease progression
  • Overall survival (OS) [ Time Frame: 5 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Brentuximab Vedotin Associated With Chemotherapy in Untreated Patients With Hodgkin Lymphoma.
Official Title  ICMJE Brentuximab Vedotin Associated With Chemotherapy in Untreated Patients With Stage I/II Unfavourable Hodgkin Lymphoma. A Randomized Phase II LYSA-FIL-EORTC Intergroup Study
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hodgkin Lymphoma
Intervention  ICMJE
  • Drug: Doxorubicin
    25mg/m2
  • Drug: Bleomycin
    10mg/m2
  • Drug: Vinblastine
    6mg/m2
  • Drug: Dacarbazine
    375mg/m2
  • Drug: Brentuximab Vedotin
    1.2 mg/kg
Study Arms  ICMJE
  • 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
    Interventions:
    • Drug: Doxorubicin
    • Drug: Bleomycin
    • Drug: Vinblastine
    • Drug: Dacarbazine
  • 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
    Interventions:
    • Drug: Doxorubicin
    • Drug: Vinblastine
    • Drug: Dacarbazine
    • Drug: Brentuximab Vedotin
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 13, 2014)
170
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 2, 2022
Actual Primary Completion Date December 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Croatia,   Denmark,   France,   Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02292979
Other Study ID Numbers  ICMJE BREACH
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party The Lymphoma Academic Research Organisation
Original Responsible Party Same as current
Current Study Sponsor  ICMJE The Lymphoma Academic Research Organisation
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Millennium Pharmaceuticals, Inc.
Investigators  ICMJE
Principal Investigator: Marc André, Pr Lymphoma Study Association
Principal Investigator: Luc Fornecker, Dr Lymphoma Study Association
PRS Account The Lymphoma Academic Research Organisation
Verification Date August 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP