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

NCT ID: NCT02298283

Last Updated: 2021-07-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2020-07-09

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

Conditions

Hodgkin Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

brentuximab vedotin

Intervention Type: DRUG

is 1.8 mg/kg administrated by IV infusion

Cyclophosphamide

Intervention Type: DRUG

1250 mg/m², IV, part of the BEACOPP chemiotherapy, D1 of 2 BEACOPP cycles, every 3 weeks

Adriamycin

Intervention Type: DRUG

35mg/m², IV, part of the BEACOPP chemiotherapy, D1 of 2 BEACOPP cycles, every 3 weeks

Oncovin

Intervention Type: DRUG

1.4 mg/m², IV, part of the BEACOPP chemiotherapy, D8 of 2 BEACOPP cycles, every 3 weeks

Bleomycin

Intervention Type: DRUG

10 mg/m², IV, part of the BEACOPP chemiotherapy, D8 of 2 BEACOPP cycles, every 3 weeks

Etoposide

Intervention Type: DRUG

200 mg/m², IV, part of the BEACOPP chemiotherapy, D1 to D3 of 2 BEACOPP cycles, every 3 weeks

Procarbazine

Intervention Type: DRUG

100 mg/m², IV, part of the BEACOPP chemiotherapy, D1 to D7 of 2 BEACOPP cycles, every 3 weeks

Prednisone

Intervention Type: DRUG

40 mg/m², IV, part of the BEACOPP chemiotherapy, D1 to D7 of 2 BEACOPP cycles, every 3 weeks

G-CSF

Intervention Type: DRUG

5 µg/kg/j, SC, D9 until GB 1.0x109/L

30 Grays

Intervention Type: RADIATION

30 Gy radiation of sites initially diagnoses + 6Gy for residual sites, 3 to 4 weeks after D1 of BEACOPP cycle 2.

Interventions

brentuximab vedotin

is 1.8 mg/kg administrated by IV infusion

Intervention Type: DRUG

Cyclophosphamide

1250 mg/m², IV, part of the BEACOPP chemiotherapy, D1 of 2 BEACOPP cycles, every 3 weeks

Intervention Type: DRUG

Adriamycin

35mg/m², IV, part of the BEACOPP chemiotherapy, D1 of 2 BEACOPP cycles, every 3 weeks

Intervention Type: DRUG

Oncovin

1.4 mg/m², IV, part of the BEACOPP chemiotherapy, D8 of 2 BEACOPP cycles, every 3 weeks

Intervention Type: DRUG

Bleomycin

10 mg/m², IV, part of the BEACOPP chemiotherapy, D8 of 2 BEACOPP cycles, every 3 weeks

Intervention Type: DRUG

Etoposide

200 mg/m², IV, part of the BEACOPP chemiotherapy, D1 to D3 of 2 BEACOPP cycles, every 3 weeks

Intervention Type: DRUG

Procarbazine

100 mg/m², IV, part of the BEACOPP chemiotherapy, D1 to D7 of 2 BEACOPP cycles, every 3 weeks

Intervention Type: DRUG

Prednisone

40 mg/m², IV, part of the BEACOPP chemiotherapy, D1 to D7 of 2 BEACOPP cycles, every 3 weeks

Intervention Type: DRUG

G-CSF

5 µg/kg/j, SC, D9 until GB 1.0x109/L

Intervention Type: DRUG

30 Grays

30 Gy radiation of sites initially diagnoses + 6Gy for residual sites, 3 to 4 weeks after D1 of BEACOPP cycle 2.

Intervention Type: RADIATION

Other Intervention Names

SGN35; Doxorubicin; Vincristin

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Lymphoma Academic Research Organisation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pauline BRICE, MD

Role: PRINCIPAL_INVESTIGATOR

Lymphoma Study Association

Thomas GASTINNE, MD

Role: PRINCIPAL_INVESTIGATOR

Lymphoma Study Association

Locations

CH Victor Dupouy

Argenteuil, , France

Polyclinique Bordeaux Nord

Bordeaux, , France

Centre François Baclesse

Caen, , France

CH de Chambéry

Chambéry, , France

CH Sud Francilien

Corbeil-Essonnes, , France

Hôpital Henri Mondor

Créteil, , France

CHU de Dijon - Hôpital le Bocage

Dijon, , France

Hôpital André Mignot

Le Chesnay, , France

Clinique Victor Hugo

Le Mans, , France

CHRU Lille - Hôpital Claude Huriez

Lille, , France

CHU de Limoges

Limoges, , France

Centre Léon Bérard

Lyon, , France

Institut Paoli Calmette

Marseille, , France

Hôpital de la Conception

Marseille, , France

CHU Montpellier - Saint ELOI

Montpellier, , France

CHU de Nantes

Nantes, , France

Hôpital Cochin

Paris, , France

Hôpital Saint Louis

Paris, , France

Hôpital de la Pitié Salpétrière

Paris, , France

CH Perpignan

Perpignan, , France

Hôpital Haut Lévêque

Pessac, , France

CHU Lyon Sud

Pierre-Bénite, , France

CHU Robert Debre

Reims, , France

CHU Pontchaillou

Rennes, , France

Centre Henri Becquerel

Rouen, , France

CHU de Strasbourg

Strasbourg, , France

I.U.C.T Oncopole

Toulouse, , France

CHU Bretonneau

Tours, , France

CHU de Brabois

Vandœuvre-lès-Nancy, , France

Gustave Roussy Cancer Campus

Villejuif, , France

Countries

France

Other Identifiers

BRAPP2

Identifier Type: -

Identifier Source: org_study_id