Clinical Trials Register

Summary
EudraCT Number:	2021-000493-29
Sponsor's Protocol Code Number:	CA224-069
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-02-16
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

Spain - AEMPS

A.2

EudraCT number

2021-000493-29

A.3

Full title of the trial

A Phase 1/2 Study of the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Relatlimab Plus Nivolumab in Pediatric and Young Adult Participants with Recurrent or Refractory Classical Hodgkin Lymphoma and Non-Hodgkin Lymphoma

Estudio en fase I/II de la seguridad, tolerabilidad, farmacocinética y eficacia preliminar de relatlimab más nivolumab en participantes pediátricos y adultos jóvenes con linfoma de Hodgkin clásico y linfoma no Hodgkin recurrentes o resistentes

A.3.1

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

Relatlimab + Nivolumab in Pediatric and Young Adult Lymphomas (RELATIVITY-069)

Relatlimab más nivolumab en participantes pediátricos y adultos jóvenes con linfoma (RELATIVITY-069)

A.4.1

Sponsor's protocol code number

CA224-069

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1264-4062

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	Bristol-Myers Squibb International Corporation
B.1.3.4	Country	Belgium
B.3.1 and B.3.2	Status of the sponsor	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 International Corporation
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bristol-Myers Squibb International Corporation
B.5.2	Functional name of contact point	GSM-CT
B.5.3	Address:
B.5.3.1	Street Address	Parc de l'Alliance - Avenue de Finlande, 4
B.5.3.2	Town/ city	Braine-l'Alleud
B.5.3.3	Post code	1420
B.5.3.4	Country	Belgium
B.5.6	E-mail	clinical.trials@bms.com

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	No
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	Anti-LAG-3 -8ml vial
D.3.2	Product code	BMS-986016
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	relatlimab
D.3.9.2	Current sponsor code	BMS-986016
D.3.9.3	Other descriptive name	BMS986016
D.3.9.4	EV Substance Code	SUB168199
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	No
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	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.2.1.1.1	Trade name	Opdivo (100 mg/10 ml)
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 - 10ml vial COMMERCIAL
D.3.2	Product code	BMS-936558
D.3.4	Pharmaceutical form	Concentrate 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	NIVOLUMAB
D.3.9.1	CAS number	946414-94-4
D.3.9.2	Current sponsor code	BMS-936558
D.3.9.3	Other descriptive name	BMS936558
D.3.9.4	EV Substance Code	SUB32944
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	No
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	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.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

Recurrent or Refractory Classical Hodgkin Lymphoma and Non-Hodgkin Lymphoma

Linfoma de Hodgkin clásico y linfoma no Hodgkin recurrentes o resistentes

E.1.1.1

Medical condition in easily understood language

Hodgkin Lymphoma and Non-Hodgkin Lymphoma

Linfoma de Hodgkin clásico y linfoma no Hodgkin

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	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10080208
E.1.2	Term	Classical Hodgkin lymphoma
E.1.2	System Organ Class	100000004864

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	10025320
E.1.2	Term	Lymphomas non-Hodgkin's B-cell
E.1.2	System Organ Class	10005329 - Blood and lymphatic system disorders

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	10025322
E.1.2	Term	Lymphomas non-Hodgkin's unspecified histology
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

Part A: To characterize the safety, tolerability, and define the MTD or RP2D for the combination of relatlimab + nivolumab in pediatric participants less than 18 years of age with R/R cHL and NHL.
Part A: To characterize the PK of relatlimab for the combination of relatlimab + nivolumab in pediatric participants less than 18 years of age with R/R cHL and NHL.
Part B: To assess the preliminary efficacy of relatlimab + nivolumab based on the RP2D from part A in participants less than or equal to 30 years old with cHL (Cohort 1).

Parte A: caracterizar la seguridad y tolerabilidad y definir la DMT o DRF2 para la combinación de relatlimab + nivolumab en participantes pediátricos menores de 18 años de edad con LHc y LNH R/R.
Parte A: caracterizar la FC de relatlimab para la combinación de relatlimab + nivolumab en participantes pediátricos menores de 18 años de edad con LHc y LNH R/R.
Parte B: evaluar la eficacia preliminar de relatlimab + nivolumab según la DRF2 de la parte A en participantes con una edad igual o inferior a 30 años con LHc (cohorte 1).

E.2.2

Secondary objectives of the trial

Part B: To assess the safety of relatlimab + nivolumab in R/R cHL (Cohort 1) and NHL (Cohort2)
Part B: To evaluate the ORR of relatlimab + nivolumab in participants ≤ 30 years of age with cHL (Cohort 1)

Parte B: evaluar la seguridad de relatlimab + nivolumab en el LHc R/R (cohorte 1) y el LNH (cohorte 2).
Parte B: evaluar la TRG de relatlimab + nivolumab en participantes de ≤ 30 años de edad con LHc (cohorte 1).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Male and female participants less than 18 years of age (Part A), and less than or equal to 30 years of age (Part B) with Recurrent or Refractory Classical Hodgkin Lymphoma (R/R cHL) (Cohort 1) and Non Hodgkin Lymphoma (NHL) (Cohort 2).
• Participants with pathologically confirmed high-risk R/R cHL, after non-response to or failure of first-line standard therapy prior to HDCT/ASCT.
• Participants with pathologically confirmed high-risk, R/R NHL after failure or non-response to first-line therapy
• Participants must have measurable FDG-PET-CT positive disease in both cHL and NHL cohorts.

- Participantes de ambos sexos menores de 18 años de edad (parte A) y con una edad igual o inferior a 30 años (parte B) con LHc (cohorte 1) y LNH (cohorte 2) R/R.
- Participantes con LHc R/R de alto riesgo confirmado anatomopatológicamente, después de ausencia de respuesta o fracaso del tratamiento estándar de primera línea antes de la QTDA/el TACM.
- Participantes con LNH R/R de alto riesgo confirmado anatomopatológicamente después de ausencia de respuesta o fracaso del tratamiento de primera línea
- Los participantes deben tener enfermedad medible positiva en la TEP-FDG-TAC en las cohortes de LHc y LNH.

E.4

Principal exclusion criteria

• Prior treatment with an anti-cytotoxic T-lymphocyte-associated protein 4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways, with the exception of anti-PD(L)-1 targeted therapies.
• Prior treatment with LAG-3-targeted agents.
• Participants with prior autologous stem cell transplantation (HDCT/ASCT).
• Participants with a history of allogeneic bone marrow transplantation and with active graft versus host disease (GVHD) and prior history of Grade > 2 GVHD.
• Participants with clinically significant systemic illnesses unrelated to the cancer as judged by the investigators, which would compromise the participant’s ability to tolerate the study treatment.
• Participants with autoimmune disease.

- Tratamiento previo con un anticuerpo contra la proteína 4 asociada a linfocitos T citotóxicos, o cualquier otro anticuerpo o fármaco dirigido específicamente a la coestimulación de los linfocitos T o a las vías de los puntos de control, con la excepción de los tratamientos dirigidos a PD(L)-1.
- Tratamiento previo con fármacos dirigidos a LAG-3.
- Participantes con trasplante autólogo de células madre (QTDA/TACM) previo.
- Participantes con antecedentes de alotrasplante de médula ósea y enfermedad de injerto contra huésped (EICH) activa y antecedentes previos de EICH de grado >2.
- Participantes con enfermedades sistémicas clínicamente significativas no relacionadas con el cáncer según el criterio de los investigadores, lo que comprometería la capacidad del participante para tolerar el tratamiento del estudio.
- Participantes con enfermedad autoinmunitaria.

E.5 End points

E.5.1

Primary end point(s)

1/Part A- Dose-limiting toxicities (DLTs), Maximum Tolerated Dose/Recommended Phase 2 Dose; (MTD/RP2D), and incidences of Adverse Events (AEs), Serious Adverse Events (SAEs), AEs leading to discontinuation, deaths and laboratory abnormalities
2/Part A- maximum observed serum concentration (Cmax), trough observed concentration (Ctrough), time to maximum concentration (Tmax), and area under the curve within a dosing interval (AUC(TAU)) for relatlimab
3/Part B- Complete Metabolic Response (CMR) rate

1/parte A: TLD, DMT/DRF2 e incidencias de AA, AAG y AA que provoquen la interrupción del tratamiento, muertes y anomalías analíticas.
2/Parte A: Cmax, Cmin, Tmax y ABC(TAU) para relatlimab.
3/Parte B: Tasa de RMC

E.5.1.1

Timepoint(s) of evaluation of this end point

1/Up to 100 days after the last dose of study Treatment
2/At specified timepoints in Section 9.5 of the protocol
3/Up to 32 weeks from last patient first treatment

1/ hasta 100 días después de la última dosis del tratamiento del estudio
2/ a ciertos tiempos especificados en la sección 9.5 del protocolo
3/ hasta 32 semanas desde el primer tratamiento del último paciente

E.5.2

Secondary end point(s)

1/Part B: Incidences of AEs, SAEs, AEs leading to discontinuation, deaths, and laboratory abnormalities
2/Part B: Overall Response Rate (ORR)

1/parte B: Incidencias de AA, AAG y AA que provoquen la interrupción del tratamiento, muertes y anomalías analíticas.
2/Parte B: tasa de respuesta global (TRG)

E.5.2.1

Timepoint(s) of evaluation of this end point

1/Up to 100 days after the last dose of study Treatment
2/Up to 2 years after LPFT

1/ Hasta 100 días después de la última dosis del tratamiento del estudio
2/ hasta 2 años después del primer tratamiento del último paciente (PTUP)

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

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability

Tolerabilidad

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Dose-finding cohort by age/weight group

Cohorte de determinación de dosis por grupo de edad / peso

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

France

Germany

Italy

Netherlands

Spain

United Kingdom

United States

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 last participant last visit in the survival follow-up period

La última visita del participante en el período de seguimiento de supervivencia

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

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)

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)

At the conclusion of the study, if the study treatment is not available as an approved treatment in the local country, participants who continue to demonstrate clinical benefit may be eligible to receive BMS-supplied study treatment for maximum of 2 years treatment duration as specified in Section 7.1. If the study treatment is not available as an approved and available treatment, study intervention may be provided via compassionate use or single named patient access requiring approval...

Al final del estudio,si el tratamiento no está disponible como un tratamiento aprobado en el país,los participantes que continúen demostrando un beneficio clínico pueden ser elegibles para recibir el tratamiento proporcionado por BMS por un máx de 2 años de duración del tratamiento.Si el tratamiento no está disponible como un tratamiento aprobado,la intervención del estudio se puede proporcionar mediante el uso compasivo o el acceso de un solo paciente designado que requiera aprobación

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	ECMC Paediatric Network
G.4.3.4	Network Country	United Kingdom

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2022-05-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-03-31

P. End of Trial
P.	End of Trial Status	Ongoing

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