Clinical Trials Register

Summary
EudraCT Number:	2017-003334-82
Sponsor's Protocol Code Number:	Uni-Koeln-3140
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-08-05
Trial 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

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A. Protocol Information

A.1

Member State Concerned

Austria - BASG

A.2

EudraCT number

2017-003334-82

A.3

Full title of the trial

Abscopal Effect of Radiotherapy and Nivolumab in anti-PD1 Pretreated Relapsed or Refractory classical Hodgkin Lymphoma -
An international multicenter Phase II trial

Abscopaler Effekt von Radiotherapie und Nivolumab bei rezidiviertem klassischen Hodgkin Lymphom unter vorheriger anti-PD1 Therapie - Eine internationale multizentrische GHSG Phase II Studie

A.3.1

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

Effect of Radiotherapy and Nivolumab in Relapsed classical Hodgkin Lymphoma

Effekt von Radiotherapie und Nivolumab bei rezidiviertem klassischen Hodgkin Lymphom

A.3.2

Name or abbreviated title of the trial where available

AERN

A.4.1

Sponsor's protocol code number

Uni-Koeln-3140

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	Bristol-Myers Squibb
B.4.2	Country	Germany
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	Trial Coordination Center
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	004922147888200
B.5.5	Fax number	004922147888188
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	Opdivo
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb Pharma EEIG
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Nivolumab
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	Opdivo
D.3.9.1	CAS number	946414-94-4
D.3.9.3	Other descriptive name	NIVOLUMAB
D.3.9.4	EV Substance Code	SUB122750
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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)	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	Yes
D.3.11.13.1	Other medicinal product type	Monoclonal anti-PD1 antibody

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

Improvement of efficacy of nivolumab in patients with relapsed or refractory classical Hodgkin Lymphoma who recently progressed on anti-PD1 therapy.

E.1.1.1

Medical condition in easily understood language

Improvement of efficacy of nivolumab in patients with relapsed or refractory classical Hodgkin Lymphoma who recently progressed on anti-PD1 therapy.

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	20.0
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

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of the trial is to show efficacy of the experimental treatment strategy.

E.2.2

Secondary objectives of the trial

Secondary objectives are to further evaluate efficacy, show safety and feasibility and perform correlative studies.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Relapsed/refractory cHL with progression while treated with an anti-PD1 antibody or
Relapsed/refractory cHL with stable disease for > 6 months as best response to ongoing anti-PD1 antibody therapy
- At least two distinct FDG-avid HL-lesions with at least 5cm distance between them, and one of them considered eligible for irradiation with 20Gy
- One but the irradiated lesion has to be outside the 10% isodose in RT planning confirmed by the Central Response Evaluation Panel (CREP)
- Age ≥ 18 years, all sexes

E.4

Principal exclusion criteria

-Nodular-lymphocyte predominant HL (NLPHL) or composite/greyzone lymphoma
-Lymphoma involving the central nervous system
-Naïve to treatment with anti-PD1 targeting antibodies
-Prior allogeneic stem-cell transplantation (alloSCT), if one or more of the following conditions are met:
a. AlloSCT conducted <12 months prior to registration for the screening phase
b. Requiring continued immunosuppression beyond 7d) at registration for the screening phase
c. History of acute graft-versus-host disease ≥°3
d. History of chronic graft-versus-host disease ≥°3

E.5 End points

E.5.1

Primary end point(s)

Abscopal response rate (ARR-6) with abscopal response centrally confirmed as restaging result after RT to a single lesion and at least four but not more than six nivolumab infusions (RE-6 result)

E.5.1.1

Timepoint(s) of evaluation of this end point

please refer to E.5.1

E.5.2

Secondary end point(s)

Overall abscopal response rate (OARR)
Overall response rate (ORR)
Duration of response (DOR)
Progression-free survival (PFS)
Overall survival (OS)
Adverse events (AE)
Feasibility aspects
Quality of life (QoL) and life situation (LS) aspects
Correlative studies

E.5.2.1

Timepoint(s) of evaluation of this end point

please refer to E.5.1

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

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

The end of the trial (EoT) will be reached with the end-of-treatment visit (final restaging) of the last patient receiving therapy within the trial, but one year after Last Patient In (LPI) at the earliest.

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.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

Yes

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)

If a patient benefits from continuous therapy within the trial, treating physician should consider to prescribe Nivo. within its indication for relapsed or refractory class. HL to continue treatment outside the trial. There will be documented FU within the trial until EoT. Thereafter the patient will be monitored by treating physician accord. to standard of care. In case of relapsed or progressive disease treating physician and patient will discuss approp. strategies.

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

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-08-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-09-02

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2024-05-04

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