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

Hodgkin Lymphoma Clinical Trial

— BRAPP2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02298283
• Other study ID #: BRAPP2
• Status: Completed
• Phase: Phase 2
• Start date: April 2015
• Est. completion date: July 9, 2020

Study information

• Verified date: July 2021
• 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 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).

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: July 9, 2020
• Est. primary completion date: July 9, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Hodgkin Disease
• Hodgkin Lymphoma
• Lymphoma

Intervention

Drug:
• brentuximab vedotin
is 1.8 mg/kg administrated by IV infusion
• Cyclophosphamide
1250 mg/m², IV, part of the BEACOPP chemiotherapy, D1 of 2 BEACOPP cycles, every 3 weeks
• Adriamycin
35mg/m², IV, part of the BEACOPP chemiotherapy, D1 of 2 BEACOPP cycles, every 3 weeks
• Oncovin
1.4 mg/m², IV, part of the BEACOPP chemiotherapy, D8 of 2 BEACOPP cycles, every 3 weeks
• Bleomycin
10 mg/m², IV, part of the BEACOPP chemiotherapy, D8 of 2 BEACOPP cycles, every 3 weeks
• Etoposide
200 mg/m², IV, part of the BEACOPP chemiotherapy, D1 to D3 of 2 BEACOPP cycles, every 3 weeks
• Procarbazine
100 mg/m², IV, part of the BEACOPP chemiotherapy, D1 to D7 of 2 BEACOPP cycles, every 3 weeks
• Prednisone
40 mg/m², IV, part of the BEACOPP chemiotherapy, D1 to D7 of 2 BEACOPP cycles, every 3 weeks
• 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.

Locations

Country	Name	City	State
France	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	Creteil
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	Hôpital de la Conception	Marseille
France	Institut Paoli Calmette	Marseille
France	CHU Montpellier - Saint ELOI	Montpellier
France	CHU de Nantes	Nantes
France	Hôpital Cochin	Paris
France	Hôpital de la Pitié Salpétrière	Paris
France	Hôpital Saint Louis	Paris cedex 10
France	CH Perpignan	Perpignan
France	Hôpital Haut Lévêque	Pessac
France	CHU Lyon Sud	Pierre Bénite Cedex
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

Sponsors (1)

Lead Sponsor	Collaborator
The Lymphoma Academic Research Organisation

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Complete Response rate (CR rate)	according to Cheson 2007	35 weeks
Secondary	Overall survival		4 years