Brentuximab Vedotin as Consolidation Treatment in Patients With Stage I/II HL and PET Positivity After 2 Cycles of ABVD (BRAPP2)

Brentuximab Vedotin as Consolidation Treatment in Patients With Stage I/II Hodgkin's Lymphoma and FDG-PET Positivity After 2 Cycles of ABVD

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).

Study Overview

• Status: Completed
• Conditions: Hodgkin Lymphoma
• Intervention / Treatment: Drug: brentuximab vedotin; Drug: Cyclophosphamide; Drug: Adriamycin; Drug: Oncovin; Drug: Bleomycin; Drug: Etoposide; Drug: Procarbazine; Drug: Prednisone; Drug: G-CSF; Radiation: 30 Grays

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

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Argenteuil, France, 95100
    • CH Victor Dupouy
  • Bordeaux, France, 33300
    • Polyclinique Bordeaux Nord
  • Caen, France, 14076
    • Centre François Baclesse
  • Chambéry, France, 73011
    • CH de Chambery
  • Corbeil-Essonnes, France, 91108
    • CH SUd Francilien
  • Creteil, France, 94010
    • Hopital Henri Mondor
  • Dijon, France, 21034
    • CHU de Dijon - Hopital le Bocage
  • Le Chesnay, France, 78157
    • Hôpital André Mignot
  • Le Mans, France, 72000
    • Clinique Victor Hugo
  • Lille, France, 59037
    • CHRU LILLE - Hôpital Claude Huriez
  • Limoges, France, 87042
    • chu de Limoges
  • Lyon, France, 69008
    • Centre Leon Bérard
  • Marseille, France, 13385
    • Hôpital De La Conception
  • Marseille, France, 13273
    • Institut Paoli Calmette
  • Montpellier, France, 34295
    • CHU Montpellier - Saint ELOI
  • Nantes, France, 44093
    • CHU de Nantes
  • Paris, France, 75651
    • Hopital de la Pitie Salpetriere
  • Paris, France, 75004
    • Hôpital COCHIN
  • Paris cedex 10, France, 75475
    • Hopital Saint Louis
  • Perpignan, France, 66046
    • CH Perpignan
  • Pessac, France, 33604
    • Hopital Haut Leveque
  • Pierre Bénite Cedex, France, 69495
    • CHU Lyon Sud
  • Reims, France, 51092
    • CHU Robert Debré
  • Rennes, France, 35033
    • CHU Pontchaillou
  • Rouen, France, 76000
    • Centre Henri Becquerel
  • Strasbourg, France, 67098
    • CHU de Strasbourg
  • Toulouse, France, 31059
    • I.U.C.T Oncopole
  • Tours, France, 37044
    • CHU Bretonneau
  • Vandœuvre-lès-Nancy, France, 54511
    • CHU de Brabois
  • Villejuif, France, 94805
    • Gustave Roussy Cancer Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: study treatment; 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

Drug: brentuximab vedotin; is 1.8 mg/kg administrated by IV infusion; Other Names: SGN35; Drug: Cyclophosphamide; 1250 mg/m², IV, part of the BEACOPP chemiotherapy, D1 of 2 BEACOPP cycles, every 3 weeks; Drug: Adriamycin; 35mg/m², IV, part of the BEACOPP chemiotherapy, D1 of 2 BEACOPP cycles, every 3 weeks; Other Names: Doxorubicin; Drug: Oncovin; 1.4 mg/m², IV, part of the BEACOPP chemiotherapy, D8 of 2 BEACOPP cycles, every 3 weeks; Other Names: Vincristin; Drug: Bleomycin; 10 mg/m², IV, part of the BEACOPP chemiotherapy, D8 of 2 BEACOPP cycles, every 3 weeks; Drug: Etoposide; 200 mg/m², IV, part of the BEACOPP chemiotherapy, D1 to D3 of 2 BEACOPP cycles, every 3 weeks; Drug: Procarbazine; 100 mg/m², IV, part of the BEACOPP chemiotherapy, D1 to D7 of 2 BEACOPP cycles, every 3 weeks; Drug: Prednisone; 40 mg/m², IV, part of the BEACOPP chemiotherapy, D1 to D7 of 2 BEACOPP cycles, every 3 weeks; Drug: G-CSF; 5 µg/kg/j, SC, D9 until GB 1.0x109/L; Radiation: 30 Grays; 30 Gy radiation of sites initially diagnoses + 6Gy for residual sites, 3 to 4 weeks after D1 of BEACOPP cycle 2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	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.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival		4 years
Complete Response rate (CR rate)	according to Cheson 2007	35 weeks

Collaborators and Investigators

• Sponsor: The Lymphoma Academic Research Organisation
• Investigators: Principal Investigator: Thomas GASTINNE, MD, Lymphoma Study Association

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (ACTUAL): July 9, 2020
• Study Completion (ACTUAL): July 9, 2020

Study Registration Dates

• First Submitted: November 13, 2014
• First Submitted That Met QC Criteria: November 20, 2014
• First Posted (ESTIMATE): November 21, 2014

Study Record Updates

• Last Update Posted (ACTUAL): July 26, 2021
• Last Update Submitted That Met QC Criteria: July 23, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Hodgkin lymphoma; HL; brentuximab vedotin
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Cyclophosphamide; Etoposide; Prednisone; Doxorubicin; Liposomal doxorubicin; Vincristine; Bleomycin; Brentuximab Vedotin; Procarbazine
• Other Study ID Numbers: BRAPP2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO