Clinical Trials Register

Summary
EudraCT Number:	2013-003990-89
Sponsor's Protocol Code Number:	Uni-Koeln-1707
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-12-07
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Sweden - MPA

A.2

EudraCT number

2013-003990-89

A.3

Full title of the trial

Brentuximab vedotin or B-CAP in the treatment of older patients with newly diagnosed classical Hodgkin Lymphoma – a GHSG-NLG Intergroup Phase II trial –

Brentuximab vedotin eller B-CAP för behandling av äldre med nydiagnosticerat klassiskt Hodgkin lymfom
– en fas II studie av den Tyska Hodgkin-studiegruppen (GHSG-German Hodgkin Study Group) i samarbete med den Nordiska lymfomgruppen (NLG) –

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Immunochemotherapy as new treatment for older Patients with Hodgkin Lymphoma

Immunokemoterapi som ny behandling av äldre patienter med Hodgkin lymfom

A.4.1

Sponsor's protocol code number

Uni-Koeln-1707

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02191930

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	University of Cologne
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Millennium Pharmaceutical Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	German Hodgkin Study Group
B.5.2	Functional name of contact point	German Hodgkin Study Group
B.5.3	Address:
B.5.3.1	Street Address	Gleueler Straße 269-273
B.5.3.2	Town/ city	Cologne
B.5.3.3	Post code	50935
B.5.3.4	Country	Germany
B.5.4	Telephone number	0049221478 88200
B.5.5	Fax number	0049221478 88188
B.5.6	E-mail	ghsg@uk-koeln.de

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	ADCETRIS
D.2.1.1.2	Name of the Marketing Authorisation holder	Millennium Pharmaceuticals Inc.
D.2.1.2	Country which granted the Marketing Authorisation	United States
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Adcetris
D.3.4	Pharmaceutical form	Lyophilisate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	brentuximab vedotin
D.3.9.1	CAS number	914088-09-8
D.3.9.3	Other descriptive name	BRENTUXIMAB VEDOTIN
D.3.9.4	EV Substance Code	SUB32397
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DOXORUBICIN
D.3.9.1	CAS number	23214-92-8
D.3.9.4	EV Substance Code	SUB06391MIG
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Lyophilisate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CYCLOPHOSPHAMIDE
D.3.9.1	CAS number	6055-19-2
D.3.9.4	EV Substance Code	SUB16414MIG
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 4
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PREDNISONE
D.3.9.3	Other descriptive name	PREDNISONE
D.3.9.4	EV Substance Code	SUB10020MIG
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Treatment of older patients with newly diagnosed classical Hodgkin lymphoma

Behandling av äldre patienter med nydiagnostiserat klassiskt Hodgkin lymfom

E.1.1.1

Medical condition in easily understood language

classical Hodgkin lymphoma

klassiskt Hodgkin lymfom

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.1
E.1.2	Level	HLGT
E.1.2	Classification code	10025319
E.1.2	Term	Lymphomas Hodgkin's disease
E.1.2	System Organ Class	10005329 - Blood and lymphatic system disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objectives are to show efficacy of B-CAP and brentuximab vedotin monotherapy

E.2.2

Secondary objectives of the trial

Secondary objectives are to show the safety and feasibility of B-CAP and brentuximab vedotin.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

B-CAP group:
-Histologically proven classical Hodgkin lymphoma
-First diagnosis, no previous treatment except prephase as outlined
-Age: 60 years or older
-Advanced stages: Stage IIB with large mediastinal mass and/or extranodal lesions, stage III or IV disease
-ECOG performance status ≤ 2 or ≤ 3 if due to HL
-CIRS-G score of ≤ 6 and ≤ 3 per organ system (except score 4 for eye, ear, nose and throat)
-Negative HIV test
-Screening laboratory values must meet the following criteria: Hemoglobin ≥8.0 g/dl, WBC ≥1500/μl; neutrophils ≥1500/μl; platelets ≥75,000/μl (Unless due to HL) Alkaline phosphatase <3 ULN, AST or ALT <3 ULN, serum total bilirubin ≤1.5 ULN (unless diagnosed with Gilbert’s Syndrome)* INR 2 and an aPTT 2 ULN unless due to anticoagulation Creatinine clearance > 40 ml/min as estimated by the Cockroft-Gault formula*
-Life expectancy > 3 months

Brentuximab vedotin single agent group:
-Histologically proven classical Hodgkin lymphoma
-First diagnosis, no previous treatment
-Age: 60 years or older stage IA to IVB
-CIRS-G score of ≥ 7 or 4 in one organ system (except score 4 for eye, ear, nose and throat)
-Patients not eligible to curative poly-chemotherapy at the investigators judgment
-Negative HIV test
-Screening laboratory values must meet the following criteria: Hemoglobin ≥8.0 g/dl, WBC ≥1500/μl; neutrophils ≥1500/μl; platelets ≥75,000/μl (Unless due to HL) Alkaline phosphatase <3 ULN, AST or ALT <3 ULN, serum total bilirubin ≤1.5 ULN (unless diagnosed with Gilbert’s Syndrome)* INR 2 and an aPTT 2 ULN unless due to anticoagulation Creatinine clearance > 40 ml/min as estimated by the Cockroft-Gault formula*

E.4

Principal exclusion criteria

B-CAP group:
-Composite lymphoma or nodular lymphocyte- predominant Hodgkin lymphoma (NLPHL)
-Prior chemotherapy or radiation for HL except prephase as outlined in the protocol
-Prior chemotherapy containing anthracyclines
-Concurrent disease which precludes protocol treatment, in particular the following conditions: Chronic obstructive pulmonary disease (requiring ≥ 2 inpatient treatments due to exacerbation within 1 year); History of myocardial infarction ≤ 6 months prior to first dose of study drug; Symptomatic ischemic heart disease, ongoing arrhythmias of Grade > 2, or any other cardiac condition (e.g. pericardial effusion restrictive cardiomyopathy) within 6 months prior to first dose of study drug. Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed; Heart failure ≥ NYHA II and/or EF <50% (MUGA scan or echocardiography); Uncontrolled hypertension despite appropriate medication; Uncontrolled active infection; Chronic active or persisting (positive PCR) hepatitis B and/or hepatitis C
-Ongoing long-term (i.e. >6 months) ingestion of corticosteroids (e.g. for chronic polyarthritis) or antineoplastic drugs (e.g. methotrexate)
-Peripheral neuropathy greater than CTC Grade 1
-Patient’s lack of accountability, inability to appreciate the nature, meaning and consequences of the trial and to formulate his/her own wishes correspondingly
-Non-compliance General intolerance of any protocol medication Patients who have a relationship of dependence or
employer-employee relationship to the sponsor or the investigator
-Committal to an institution on judicial or official order Participation in another interventional trial that could interact with this trial

Brentuximab vedotin single agent group:
-Composite lymphoma or nodular lymphocyte- predominant Hodgkin lymphoma (NLPHL)
-Prior chemotherapy or radiation for HL except prephase as outlined in the protocol
-Ongoing long-term (i.e. >6 months) ingestion of corticosteroids (e.g. for chronic polyarthritis) or antineoplastic drugs (e.g. methotrexate)
-Peripheral neuropathy greater than CTC Grade 1
-Patient’s lack of accountability, inability to appreciate the nature, meaning and consequences of the trial and to formulate his/her own wishes correspondingly
-Non-compliance General intolerance of any protocol medication Patients who have a relationship of dependence or employer-employee relationship to the sponsor or the investigator
-Committal to an institution on judicial or official order
-Participation in another interventional trial that could interact with this trial

E.5 End points

E.5.1

Primary end point(s)

Primary endpoint of the study is the objective response rate (ORR), defined as the proportion of patients having CR, CRr or PR in the centrally reviewed restaging after six cycles of chemotherapy.

E.5.1.1

Timepoint(s) of evaluation of this end point

see E.5.1

E.5.2

Secondary end point(s)

Secondary endpoints include the complete remission rate assessed after the end of treatment, progression-free survival (PFS) at three years, overall survival (OS), OSHL and PFSHL at three years (defined as OS and PFS but deaths for known reasons other than HL or toxicity of treatment are censored and not considered as failures), the frequency of adverse events and the relative dose intensity of the novel brentuximab vedotin-containing B-CAP regimen or brentuximab vedotin.

E.5.2.1

Timepoint(s) of evaluation of this end point

see E.5.2

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Final analysis

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.3

Elderly (>=65 years)

Yes

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

The attending physician and patient discuss and decide together about the (after-) care

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	German Hodgkin Study Group
G.4.3.4	Network Country	Germany
G.4 Investigator Network to be involved in the Trial: 2
G.4.1	Name of Organisation	NLG - Nordic Lymphoma Group
G.4.3.4	Network Country	Norway

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-03-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-01-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-03-16

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials