Clinical Trials Register

Summary
EudraCT Number:	2011-005474-38
Sponsor's Protocol Code Number:	YZIRIT
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2011-12-12
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2011-005474-38

A.3

Full title of the trial

89Zr-Rituximab PET/CT-Imaging and Dosimetry and 90Y-Rituximab Radioimmunotherapy in CD20+ B-Cell lymphoma

A.3.1

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

The use of isotope-bound antibodies to visualize and subsequently treat B-cell lymphoma

A.3.2

Name or abbreviated title of the trial where available

YZIRIT

A.4.1

Sponsor's protocol code number

YZIRIT

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	Institut Jules Bordet
B.1.3.4	Country	Belgium
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	FNRS - Télévie
B.4.2	Country	Belgium
B.4.1	Name of organisation providing support	Les Amis de Bordet
B.4.2	Country	Belgium
B.4.1	Name of organisation providing support	National Cancer Plan
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	Institut Jules Bordet
B.5.2	Functional name of contact point	Vaes Mélanie
B.5.3	Address:
B.5.3.1	Street Address	Boulevard de Waterloo 121
B.5.3.2	Town/ city	Brussels
B.5.3.3	Post code	1000
B.5.3.4	Country	Belgium
B.5.4	Telephone number	003225413747
B.5.5	Fax number	003225413224
B.5.6	E-mail	mvaes@ulb.ac.be

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	89Zr-N-sucDf-rituximab
D.3.2	Product code	none
D.3.4	Pharmaceutical form	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	89Zr-SucDf-Rituximab
D.3.10	Strength
D.3.10.1	Concentration unit	MBq/ml megabecquerel(s)/millilitre
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	0.9 to 7.2
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	Yes
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 antibody
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	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	90Y-DOTA-rituximab
D.3.4	Pharmaceutical form	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	90Y-DOTA-rituximab
D.3.10	Strength
D.3.10.1	Concentration unit	MBq/ml megabecquerel(s)/millilitre
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	50 to 100
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	Yes
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 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

CD20 positive Lymphoma

E.1.1.1

Medical condition in easily understood language

patients with a lymphoma of B cells that expresses CD20

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	14.0
E.1.2	Level	PT
E.1.2	Classification code	10003902
E.1.2	Term	B-cell lymphoma recurrent
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Evaluation of safety of Zirconium-89 (89Zr)- rituximab chimeric anti-CD20 antibody for PET/CT imaging and dosimetry.
Evaluation of safety of Yttrium-90 (90Y)-rituximab chimeric anti-CD20 antibody radioimmunotherapy in patients with B-cell lymphoma who are in partial remission or progressive disease

E.2.2

Secondary objectives of the trial

-Evaluation of the efficacy of 90Y-rituximab treatment by assessment of metabolic response status (by FDG-PET/CT-imaging) and progression-free survival.

-Evaluation of the efficacy of 89Zr-rituximab PET/CT-imaging

-Evaluation of a voxel based dosimetry model based on PET/CT imaging using 89Zr-rituximab

-Diagnostic comparison of 89Zr-rituximab-PET/CT with FDG-PET/CT

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Evaluation of the impact of (cold) anti-CD20 antibodies (rituximab) on targeting of a second radiolabelled anti-CD20-Ab (89Zr-/90Y-rituximab)

Objective: Evaluation of the influence of infusion of unlabelled (cold) rituximab on the distribution of the radio-immunoconjugate

E.3

Principal inclusion criteria

• Histologically confirmed (according to the REAL/WHO classification) CD20 positive lymphomas

• Patients with a PR or PD

• Failed at least one regimen of standard treatment/chemotherapy

• Age 18 years or older

• World Health Organization (WHO) performance status of 0 to 2

• Absolute Neutrophil Count (ANC) of 1.5 x 109/L or higher

• Haemoglobin (Hb) of 9 g/dl or higher

• Platelet count of 100 x 109/L or higher

• Life expectancy of at least 6 months

• Written informed consent obtained according to local guidelines

• For patients with ≥ 3 prior cytotoxic treatment regimens and/or patients previously treated with stem cell transplantation, a bone marrow or peripheral blood stem cell harvest is mandatory to rescue unexpected marrow toxicity from the procedure.

E.4

Principal exclusion criteria

• Patients who have not recovered from the toxic effects of previous treatment

• Any other uncontrolled malignancy except non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma

• Patients with known HIV positivity

• Patients who are positive for HCV, HbsAG or other active infection uncontrolled by treatment

• Patients with abnormal liver function: total bilirubin > 2 x ULN or ALT > 3 x ULN

• Patients with abnormal renal function: serum creatinine> 2 x ULN

• Known anti-chimeric antibody (HACA) reactivity or hypersensitivity to murine antibodies or proteins

• Female patients who are pregnant or breast feeding, or adults of reproductive potential not employing an effective method of birth control. (Women of childbearing potential must have a negative serum pregnancy test at study entry)

• Concurrent severe and/or uncontrolled medical disease (ie. uncontrolled diabetes, conges¬tive heart failure, myocardial infarction within 6 months of the study, unstable and uncon¬trolled hypertension, chronic renal disease, or active uncontrolled infection), which could compromise participation in the study.

• Patients who received investigational drugs less than 4 weeks before entry in this study or who have not as yet recovered from the toxic effects of such therapy

• Patients who underwent surgery within 4 weeks of entering the study or patients who have not as yet recovered from the side-effects of such treatment

• Patients with a history of psychological illness or condition which could interfere with his ability to understand the requirements of the study (this includes alcoholism/drug addiction)

• Patients unwilling or unable to comply with the protocol

E.5 End points

E.5.1

Primary end point(s)

Evaluation of safety of Zirconium-89 (89Zr)- rituximab chimeric anti-CD20 antibody for PET/CT imaging and dosimetry.

Evaluation of safety of Yttrium-90 (90Y)-rituximab chimeric anti-CD20 antibody radioimmunotherapy in patients with B-cell lymphoma who are in partial remission or progressive disease

E.5.1.1

Timepoint(s) of evaluation of this end point

Weekly evaluation of the toxicity during first 3 months
Evaluation of late toxicity every 3 months during 2 years follow-up

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

-Response assessment by FDG-PET three months after administration of the treatment
- other end points will be evaluated at the end of the study with an interim analysis 2 years after the inclusion of the first patient

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

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

Yes

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)

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

First combined administration of the diagnostic and therapeutic radioimmunoconjugate

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

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.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

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

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

LVLS

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

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.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)

expected normal treatment

G. Investigator Networks to be involved in the Trial

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-02-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-03-08

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

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