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Clinical Trial Results:
Brentuximab vedotin as consolidation treatment in patients with stage I/II Hodgkin’s lymphoma and FDG-PET positivity after 2 cycles of ABVD

Summary
EudraCT number	2013-000734-35
Trial protocol	FR BE
Global end of trial date	09 Jul 2020

Results information
Results version number	v1(current)
This version publication date	17 Jul 2021
First version publication date	17 Jul 2021
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

BRAPP2

ISRCTN number

US NCT number

NCT02298283

WHO universal trial number (UTN)

Sponsor organisation name

LYSARC

Sponsor organisation address

Centre Hospitalier Lyon-Sud Bâtiment 2D , PIERRE-BÉNITE Cedex, France, 69495

Public contact

Clinical Project Management, LYSARC, brapp2@lysarc.org

Scientific contact

Pauline BRICE Coordinating Investigator, LYSA HDJ Hématologie Hôpital Saint Louis, pauline.brice@aphp.fr

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

09 Jul 2020

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

09 Jul 2020

Was the trial ended prematurely?

Main objective of the trial

Progression free survival (PFS) at 2 years in patients with stage I/II Hodgkin’s lymphoma and FDG-PET positivity after 2 cycles of ABVD receiving brentuximab vedotin as consolidation treatment

Protection of trial subjects

TBC by Project Manager

Background therapy

ABVD: Adriamycin, Bleomycin, Vinblastine and DTIC/Dacarbazine BEACOPPescalated: Bleomycin, Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, Procarbazine and Prednisone IFRT (Involved Field Radiotherapy)

Evidence for comparator

Not Applicable

Actual start date of recruitment

09 Apr 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

France: 47

Country: Number of subjects enrolled

Belgium: 1

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

FRANCE from 09/04/2015 to 04/04/2018 BELGIUM on 29/01/2018

Screening details

Inclusion following FDG-PET positivity after 2 cycles of ABVD => 49 patients enrolled One patient withdrew his consent before induction treatment => 47 patients in Induction

Period 1 title

Induction

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Blinding implementation details

Not Applicable

BEACOPP + IFRT

Arm description

Arm type

Experimental

Investigational medicinal product name

BEACOPP

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Cyclophosphamide 1250 mg/m² i.v. D1 Doxorubicin 35 mg/m² i.v. D1 Vincristine 1.4 mg/m² i.v.(max.2mg) D8 Bléomycine 10 mg/m² i.v J8 Etoposide 200 mg/m²/j i.v. D1 à D3 Procarbazine 100 mg/m²/j p.o. D1 à D7 Prednisone 40 mg/m²/j p.o. D1 à D7 G-CSF 5 µg/kg/j s.c. J9 until GB 1.0x109/L ________________________________________ 2 cycles of 21 days

Number of subjects in period 1	BEACOPP + IFRT
Started	48
Completed	41
Not completed	7
Consent withdrawn by subject	1
Progression	4
Protocol deviation	1
Lack of efficacy	1

Period 2 title

Consolidation

Is this the baseline period?

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Blinding implementation details

Not Applicable

Brentuximab vedotin

Arm description

Arm type

Experimental

Investigational medicinal product name

Brentuximab Vedotin

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

1.8 mg/kg starting 4 to 6 weeks after standard radiotherapy. 8 cycles, one cycle is 3 weeks

Number of subjects in period 2	Brentuximab vedotin
Started	41
Completed	35
Not completed	6
Consent withdrawn by subject	1
Adverse event, non-fatal	4
Progression	1

Baseline characteristics

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Reporting group title

Induction

Reporting group description

Reporting group values	Induction	Total
Number of subjects	48	48
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (inter-quartile range (Q1-Q3))	36 (24 to 42)	-
Gender categorical
Units: Subjects
Female	23	23
Male	25	25

Subject analysis set title

Efficacy set

Subject analysis set type

Full analysis

Subject analysis set description

The efficacy set includes all included patients who have received at least one administration of brentuximab vedotin treatment.

Subject analysis set title

Safety set

Subject analysis set type

Safety analysis

Subject analysis set description

The safety set is defined as all patients who have received at least one dose of brentuximab vedotin.

Subject analysis sets values	Efficacy set	Safety set
Number of subjects	41	41
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (inter-quartile range (Q1-Q3))	33.8 (24 to 36)	33.8 (24 to 36)
Gender categorical
Units: Subjects
Female	22	22
Male	19	19

End points

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Reporting group title

BEACOPP + IFRT

Reporting group description

Reporting group title

Brentuximab vedotin

Reporting group description

Subject analysis set title

Efficacy set

Subject analysis set type

Full analysis

Subject analysis set description

The efficacy set includes all included patients who have received at least one administration of brentuximab vedotin treatment.

Subject analysis set title

Safety set

Subject analysis set type

Safety analysis

Subject analysis set description

The safety set is defined as all patients who have received at least one dose of brentuximab vedotin.

Primary: PFS at 2 years according to investigator assessment

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End point title

PFS at 2 years according to investigator assessment ^[1]

End point description

Progression free survival (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. If a subject has not progressed or died, PFS is censored at the time of last visit with adequate assessment.

End point type

Primary

End point timeframe

at 2 years

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: As per internal LYSARC guidelines, no statistical analysis to be specified for Phase II trial with only one arm and survival endpoint as primary endpoint.

End point values	Efficacy set
Number of subjects analysed	41
Units: percent
number (confidence interval 95%)	90.0 (75.5 to 96.1)

Attachments

PFS

No statistical analyses for this end point

Secondary: CRR at the end of treatment according to Cheson 2007

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End point title

CRR at the end of treatment according to Cheson 2007

End point description

Assessment of response is based on the International Workshop to Standardize Response criteria for NHL (Criteria for evaluation of response in Non-Hodgkin’s lymphoma (Cheson, 2007)). Patient with “not-evaluated” response or without response assessment (due to whatever reason) are considered as missing and are not included in the calculation of complete response rate (CRR).

End point type

Secondary

End point timeframe

At the end of treatment i.e. after 8 cycles of brentuximab vedotin or after last treatment dose in case of permanent treatment discontinuation

End point values	Efficacy set
Number of subjects analysed	39
Units: percent
number (confidence interval 95%)	87.2 (72.57 to 95.70)

No statistical analyses for this end point

Secondary: OS at 2 years

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End point title

OS at 2 years

End point description

OVerall survival (OS) is measured from the date of the first cycle of ABVD to the date of death from any cause. Alive patients are censored at their last follow-up date.

End point type

Secondary

End point timeframe

at 2 years

End point values	Efficacy set
Number of subjects analysed	41
Units: percent
number (confidence interval 95%)	97.5 (83.5 to 99.6)

Attachments

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Before treatment = between informed consent and BEACOPP C1D1 Induction = between 1st administration of BEACOPP and 1st administration of brentuximab vedotin Consolidation = from 1st administration of brentuximab vedotin Overall

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

Reporting group title

Before treatment

Reporting group description

Reporting group title

Induction

Reporting group description

Reporting group title

Consolidation

Reporting group description

Reporting group title

Overall

Reporting group description

Serious adverse events	Before treatment	Induction	Consolidation	Overall
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 41 (2.44%)	12 / 41 (29.27%)	3 / 41 (7.32%)	15 / 41 (36.59%)
number of deaths (all causes)	0	0	1	1
number of deaths resulting from adverse events	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papillary thyroid cancer
subjects affected / exposed	1 / 41 (2.44%)	1 / 41 (2.44%)	0 / 41 (0.00%)	2 / 41 (4.88%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Radiation pneumonitis
subjects affected / exposed	0 / 41 (0.00%)	0 / 41 (0.00%)	1 / 41 (2.44%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Venous thrombosis
subjects affected / exposed	0 / 41 (0.00%)	0 / 41 (0.00%)	1 / 41 (2.44%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Tachycardia
subjects affected / exposed	0 / 41 (0.00%)	0 / 41 (0.00%)	1 / 41 (2.44%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
Hospitalisation
subjects affected / exposed	0 / 41 (0.00%)	1 / 41 (2.44%)	0 / 41 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Febrile neutropenia
subjects affected / exposed	0 / 41 (0.00%)	5 / 41 (12.20%)	0 / 41 (0.00%)	5 / 41 (12.20%)
occurrences causally related to treatment / all	0 / 0	6 / 6	0 / 0	6 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Febrile bone marrow aplasia
subjects affected / exposed	0 / 41 (0.00%)	3 / 41 (7.32%)	0 / 41 (0.00%)	3 / 41 (7.32%)
occurrences causally related to treatment / all	0 / 0	0 / 4	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Vomiting
subjects affected / exposed	0 / 41 (0.00%)	1 / 41 (2.44%)	0 / 41 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
subjects affected / exposed	0 / 41 (0.00%)	1 / 41 (2.44%)	0 / 41 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Bartholinitis
subjects affected / exposed	0 / 41 (0.00%)	1 / 41 (2.44%)	0 / 41 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 41 (0.00%)	1 / 41 (2.44%)	0 / 41 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Before treatment	Induction	Consolidation	Overall
Total subjects affected by non serious adverse events
subjects affected / exposed	0 / 41 (0.00%)	0 / 41 (0.00%)	23 / 41 (56.10%)	23 / 41 (56.10%)
Nervous system disorders
Nervous system disorders
Additional description: Neuropathy peripheral
subjects affected / exposed	0 / 41 (0.00%)	0 / 41 (0.00%)	12 / 41 (29.27%)	12 / 41 (29.27%)
occurrences all number	0	0	14	14
Blood and lymphatic system disorders
Blood and lymphatic system disorders
Additional description: Neutropenia Leukopenia Lymphopenia
subjects affected / exposed	0 / 41 (0.00%)	0 / 41 (0.00%)	3 / 41 (7.32%)	3 / 41 (7.32%)
occurrences all number	0	0	4	4
General disorders and administration site conditions
General disorders and administration site conditions
Additional description: Asthenia Chest discomfort Oedema peripheral
subjects affected / exposed	0 / 41 (0.00%)	0 / 41 (0.00%)	3 / 41 (7.32%)	3 / 41 (7.32%)
occurrences all number	0	0	3	3
Gastrointestinal disorders
Gastrointestinal disorders
Additional description: Constipation
subjects affected / exposed	0 / 41 (0.00%)	0 / 41 (0.00%)	1 / 41 (2.44%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders
Additional description: Lung disorder Pulmonary embolism Rhinorrhoea
subjects affected / exposed	0 / 41 (0.00%)	0 / 41 (0.00%)	3 / 41 (7.32%)	3 / 41 (7.32%)
occurrences all number	0	0	3	3
Infections and infestations
Infections and infestations
Additional description: Bronchitis Herpes zoster Influenza Nasopharyngitis Sinusitis Urinary tract infection Viral infection Vulvovaginal mycotic infection
subjects affected / exposed	0 / 41 (0.00%)	0 / 41 (0.00%)	8 / 41 (19.51%)	8 / 41 (19.51%)
occurrences all number	0	0	10	10

More information

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Were there any global substantial amendments to the protocol? Yes

12 Oct 2014

New version of the protocol V2 => V3 : change in inclusion and Exclusion criteria and biological exams New version of ICF

06 Nov 2014

New version of ICF (new exams tab)

05 Nov 2015

New Investigators Brochure Version 13 (ICF modification + addendum)

23 Feb 2017

New country involved in the study : Belgium New version of protocol V5 Clarification regarding one inclusion criteria

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results:
Brentuximab vedotin as consolidation treatment in patients with stage I/II Hodgkin’s lymphoma and FDG-PET positivity after 2 cycles of ABVD

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: PFS at 2 years according to investigator assessment

Primary: PFS at 2 years according to investigator assessment

Secondary: CRR at the end of treatment according to Cheson 2007

Secondary: CRR at the end of treatment according to Cheson 2007

Secondary: OS at 2 years

Secondary: OS at 2 years

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

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Clinical trials

Clinical Trial Results: Brentuximab vedotin as consolidation treatment in patients with stage I/II Hodgkin’s lymphoma and FDG-PET positivity after 2 cycles of ABVD

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: PFS at 2 years according to investigator assessment

Primary: PFS at 2 years according to investigator assessment

Secondary: CRR at the end of treatment according to Cheson 2007

Secondary: CRR at the end of treatment according to Cheson 2007

Secondary: OS at 2 years

Secondary: OS at 2 years

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Brentuximab vedotin as consolidation treatment in patients with stage I/II Hodgkin’s lymphoma and FDG-PET positivity after 2 cycles of ABVD