Clinical Trials Register

Summary
EudraCT Number:	2021-001711-85
Sponsor's Protocol Code Number:	PTF202
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-09-22
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

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A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2021-001711-85

A.3

Full title of the trial

A prospective, international, multi-centre, open-label,single-arm phase II study investigating the predictive value of [68Ga]Ga-PentixaFor PET imaging in primary and isolated secondary CNS lymphoma patients

A.3.1

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

A prospective, international, multi-centre, open-label, phase II study investigating the utility of [68Ga]Ga-PentixaFor PET imaging in response assessment (evaluation of the tumour response to the applied therapy) of primary (primary tumour in brain) and isolated secondary (secondary tumour in brain after relapse of a primary tumour not located in the brain) CNS lymphoma patients

A.3.2

Name or abbreviated title of the trial where available

[68Ga]Ga-PentixaFor PET imaging in CNS lymphoma patients

A.4.1

Sponsor's protocol code number

PTF202

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	PentixaPharm GmbH
B.1.3.4	Country	Germany
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	PentixaPharm GmbH
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	PentixaPharm GmbH
B.5.2	Functional name of contact point	Senior Clinical Research Manager
B.5.3	Address:
B.5.3.1	Street Address	Bismarckstrasse 13
B.5.3.2	Town/ city	Würzburg
B.5.3.3	Post code	97080
B.5.3.4	Country	Germany
B.5.4	Telephone number	+4993199136074
B.5.5	Fax number	+4993199136078
B.5.6	E-mail	Anja.Zehnder@pentixapharm.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	[68Ga]Ga-PentixaFor
D.3.4	Pharmaceutical form	Powder for solution for injection
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	NA
D.3.9.1	CAS number	1345698-96-5
D.3.9.2	Current sponsor code	[68Ga]Ga-PTF
D.3.9.3	Other descriptive name	PENTIXAFOR
D.3.9.4	EV Substance Code	SUB196568
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	50
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	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	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

Central nervous system (CNS) lymphoma

E.1.1.1

Medical condition in easily understood language

A rare non-Hodgkin lymphoma in which malignant (cancer) cells from lymph tissue form in the brain and/or spinal cord or spread from other parts of the body to the brain and/or spinal cord

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10028997
E.1.2	Term	Neoplasm malignant
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

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the negative predictive value (NPV) of [68Ga]Ga-PentixaFor (PTF)-PET at interim examination (after 6 ± 2 weeks of induction chemotherapy) for progression-free survival (PFS).

E.2.2

Secondary objectives of the trial

TO EVALUATE : the positive predictive value of PTF-PET at interim examination for PFS, and the safety and tolerability of PTF-PET imaging,and the predictive values of PTF-PET at the end of induction chemotherapy for PFS, and the predictive values of PTF-PET at interim examination and end-of-chemotherapy-treatment for complete response(CR), and the predictive values of pre-treatment PTF-PET imaging parameters for PFS and CR, and the predictive values of interim PTF-PET imaging parameters for PFS and CR, and the predictive values of changes between pretreatment and interim PTF-PET imaging parameters for PFS. To determine the sensitivity of pre-treatment PTF-PET for CXCR4-positivity in the fraction of patients from whom biopsy tissue is available, by using histopathology as the reference standard on a patient basis. TO EVALUATE: the diagnostic agreement between PTF-PET and MRI at baseline imaging on a patient level, and the observer agreement of PTF PET

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

Scientific Accompanying Program of the PTF202 Study (Substudy):Liquid-biopsy-based genotyping in patients with CNS lymphoma to improve the diagnostic performance of [68Ga] Ga-PentixaFor PET to investigate how the level of cfDNA changes during therapy of CNS lymphoma and to be able to predict who will respond particularly well to therapy and in which patients less or more therapy should possibly be used, based on the course of cfDNA in combination with [68Ga]Ga- PentixaFor PET. However, no genes of inherited diseases or genes directly associated with cancer development will be studied.

E.3

Principal inclusion criteria

All study patients must meet all the following criteria:
1.Written informed consent obtained according to international guidelines and local laws by patient (or legally acceptable representative if the patient is temporarily legally not competent owing to his/her disease). [Note: No invasive study-specific procedures may be carried out until this consent has been given.]
2.Patient aged 18 years or above (either sex).
3.Histologically confirmed primary or secondary CNSL based on cytology/flow cytometry of cerebrospinal fluid (CSF) or brain biopsy.
4.Disease exclusively located in the CNS (primary CNSL or secondary CNSL with isolated CNS relapse). Subjects who had undergone allogeneic stem cell transplant > 12 months prior to first dose of study drug, have no evidence of active graft versus host disease, and are not on systemic immunosuppressive therapy are allowed to participate in the study.
5.At least one measurable parenchymal lesion. [Note: parenchymal CNSL is a “must”, and additional locations such as leptomeningeal disease are permitted.]
6.Previously untreated CNS disease.[Note: Previous or ongoing steroid treatment is permitted. Prophylaxis chemotherapy is not necessary, as induction chemotherapy will start within 72 hours after PTF-PET.]
7.At least one morphologically measurable lesion according to the IPCG criteria (Appendix 1).
8.Patients scheduled to undergo induction chemotherapy based on one of the following: High-dose methotrexate (HD-MTX)-based chemotherapy, ICE/DeVIC or High-dose cytarabine (HD-AraC)-based chemotherapy.
9.ECOG performance status ≤ 2 for patients aged ≥65 years;ECOG performance status ≤ 3 for patients aged <65 years.
10.Life expectancy of at least 3 months, as estimated by the investigator.
11.For women of child-bearing potential: negative pregnancy test.
12.For sexually active female patients of child-bearing potential: The patient agrees to take adequate contraceptive measures during study participation and also agrees to continue use of this method for the duration of the study and for 6 months after the last dose of PTF.
13.For male patients whose partner is of child-bearing potential: The patient is willing to ensure that he and his partner use effective contraception during the study and for 6 months after the last dose of PTF.

E.4

Principal exclusion criteria

Any patient meeting one or more of the following criteria will not be included:
1.Known hypersensitivity to [68Ga]Ga-PentixaFor or its components.
2.Contraindication for contrast-enhanced MRI as set out in the relevant institutional guidelines (e.g., pacemaker, defibrillator, aneurysm clip, metal in the body, renal insufficiency, severe claustrophobia etc.).
3.Contraindication for the use of gadolinium contrast for MRI.
4.Contraindication for PET according to institutional guidelines (weight-based, e.g. weight > 180 kg).
5.Inability to lie still for the entire imaging time.
6.Systemic lymphoma manifestation (outside the CNS).
7.Presence of active infection at screening or history of serious infection within the previous 6 weeks (except HIV infection: patients with HIV-associated primary CNSL are considered eligible).
8.Administration of another investigational medicinal product within the 30 days (or 5 excretion half-lives, whichever period is the longer) before first treatment with PTF.
[Note: Re screening may be performed to accept washout of prior agents.]
9.Current toxicity of Grade >2 from previous standard or investigational therapies (grade according to the NCI Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE 5.0).
10.For female patients: Pregnancy (existing or intended) or breast-feeding.
11.Renal impairment: Both of the following: Estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73 m2 Creatinine clearance < 60 ml/min
12.Hepatic impairment: Both of the following: Aspartate aminotransferase (AST) > 3 upper limit of normalAlanine aminotransferase (ALT) > 3 upper limit of normal
13.Presence of any unstable systemic disease (including, but not limited to, active infection, uncontrolled hypertension, unstable angina, congestive heart failure, serious cardiac arrhythmia requiring medication, hepatic, renal or metabolic disease.
14.Presence of psychiatric disease, alcohol abuse or any other medical condition(s) that, in the opinion of the investigator, makes the patient unable to comply with study procedures and visits.
15. Patient weight ≤ 48 kg

E.5 End points

E.5.1

Primary end point(s)

1. to evaluate the negative predictive value (NPV) of [68Ga]Ga-PentixaFor (PTF) PET at interim examination (after 6 ± 2 weeks of induction chemotherapy) for progression-free survival (PFS).

E.5.1.1

Timepoint(s) of evaluation of this end point

Patients will be evaluated after 6 weeks of induction Chemotherapy

E.5.2

Secondary end point(s)

2. To evaluate the positive predictive value (PPV) of PTF PET at interim examination (after 6 ± 2 weeks of induction chemotherapy) for PFS.
3.To evaluate the safety and tolerability of PTF PET imaging.
4.To evaluate the predictive values of PTF PET at the end of induction chemotherapy for PFS.
5.To evaluate the predictive values of PTF PET at interim examination (after 6 ± 2 weeks of induction chemotherapy) and end-of-chemotherapy-treatment for complete response (CR).
6.To evaluate the predictive values of pre-treatment PTF PET imaging parameters for PFS and CR.
7.To evaluate the predictive values of interim (after 6 ± 2 weeks of induction chemotherapy) PTF PET imaging parameters for PFS and CR.
8.To evaluate the predictive values of changes between pre-treatment and interim (after 6 ± 2 weeks of induction chemotherapy) PTF PET imaging parameters for PFS.
9.To determine the sensitivity of pre-treatment PTF PET for CXCR4-positivity in the fraction of patients from whom biopsy tissue is available, by using histopathology (CXCR4 overexpression by immunohistochemistry, IHC) as the reference standard on a patient basis.
10.To evaluate the diagnostic agreement between PTF PET and MRI at baseline imaging on a patient level.
11.To evaluate the observer agreement of PTF PET (inter- and intra-reader agreement).

E.5.2.1

Timepoint(s) of evaluation of this end point

Patients will be evaluated after 6 ± 2 weeks of induction chemotherapy for PFS and after 6 ± 2 weeks of induction chemotherapy and end-of-chemotherapy-treatment for complete response (CR).

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

E.6.4

Safety

Yes

E.6.5

Efficacy

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.8.3

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

Denmark

France

Germany

Italy

Netherlands

United States

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Written informed consent to be obtained by authorised legal representative, if the patient is temporarily legally not competent owing to his/her disease

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.4.2.2

In the whole clinical trial

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

2022-03-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-11-26

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

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