Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruiting
Participants planned
43
Countries
6
Sites
11
Cutaneous T-cell lymphoma, a category of cancers of lymphocytes (a type of white blood cells) that primarily involve the skin
To evaluate the progression free survival rate at 48 weeks (according to EORTC-ISCL-USCLC criteria) of anti-CCR4 monoclonal antibody (mogamulizumab) and TSEB in IB-IIB cutaneous T-cell lymphoma.
Key facts
- Sponsor
- European Organisation For Research And Treatment Of Cancer
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 22 Feb 2022 → ongoing
- Decision date (initial)
- 2024-04-30
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
- Funding sources
- Kyowa Kirin Holding B.V.
External identifiers
- EU CT number
- 2022-502434-10-00
- EudraCT number
- 2019-004566-17
- ClinicalTrials.gov
- NCT04128072
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Safety, Others
To evaluate the progression free survival rate at 48 weeks (according to EORTC-ISCL-USCLC criteria) of anti-CCR4 monoclonal antibody (mogamulizumab) and TSEB in IB-IIB cutaneous T-cell lymphoma.
Secondary objectives 7
- To evaluate the overall safety
- To assess the response rate
- To assess the progression-free survival
- To assess the overall survival
- To assess the time to progression
- To evaluate the duration of response
- To evaluate the time to next significant treatment
Conditions and MedDRA coding
Cutaneous T-cell lymphoma, a category of cancers of lymphocytes (a type of white blood cells) that primarily involve the skin
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 22.0 | LLT | 10028502 | Mycosis fungoides refractory | 10029104 |
| 22.0 | LLT | 10028504 | Mycosis fungoides stage II | 10029104 |
| 20.0 | HLGT | 10025321 | Lymphomas non-Hodgkin's T-cell | 10029104 |
| 22.0 | LLT | 10028511 | Mycosis fungoides/Sezary syndrome refractory | 10029104 |
| 22.0 | LLT | 10028503 | Mycosis fungoides stage I | 10029104 |
| 22.0 | LLT | 10028512 | Mycosis fungoides/Sezary syndrome stage I | 10029104 |
| 22.0 | LLT | 10028508 | Mycosis fungoides/Sezary syndrome | 10029104 |
| 22.0 | LLT | 10028513 | Mycosis fungoides/Sezary syndrome stage II | 10029104 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | single-arm It is a phase II, multicenter, open-label, single-arm trial in patients with MF stages IB-IIB who have failed at least one prior course of systemic therapy and have not been treated with TSEB or mogamulizumab.
The treatment will be administered sequentially:
• Two cycles of mogamulizumab will be first administered, then mogamulizumab will
be stopped;
• TSEB will start 28 days after mogamulizumab cycle 2 day 1 and will be
administered over 2 weeks ;
• After 2 weeks of rest, patients will re-start mogamulizumab for a maximum of 18
months (after protocol treatment start) unless disease progression or the occurrence of
another withdrawal criterion.
The primary objective is to determine the antitumor activity of mogamulizumab plus TSEB,
assessed in term of the progression free survival rate at 48 weeks (according to EORTCISCL-
USCLC criteria).
The secondary endpoints include evaluation of overall safety, response rate (of
mogamulizumab alone and the combination), overall survival, time to progression, duration
of response and time to next significant treatment.
A total of 43 patients will be registered.
|
Not Applicable | None |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- Males and female subjects ≥ 18 years
- Mycosis fungoides stage IB, IIA, IIB
- Subjects who have failed at least one prior course of systemic therapy. Psoralen plus ultraviolet light therapy (PUVA) is not considered to be a systemic therapy
- Adequate haematological and organ function
- Signed informed consent
Exclusion criteria 4
- Prior treatment with mogamulizumab
- Known hypersensitivity to CHO cell products or any component of the mogamulizumab formulation
- Significant uncontrolled intercurrent illness
- Prior TSEB treatment with at least one of the following conditions: • Patient has received high-dose TSEB (>30 Gray) • Patient has received TSEB ((including low-dose [12 Gray]) within 12 months before enrolment
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Progression Free Survival Rate, at 48 weeks after start of mogamulizumab (PFSR-48).
Secondary endpoints 8
- Overall safety of both mogamulizumab and TSEB.
- Response rate (RR) to both mogamulizumab and TSEB. Time Frame: From the first patient treatment start till 48 weeks as of last patient in Proportion of patients achieving partial response or complete response according to EORTC-ISCL-USCLC criteria
- Progression-free survival (PFS).
- Overall survival (OS).
- Time to progression.
- Duration of response.
- Time to next treatment.
- Exploratory endpoints: Quality of life: Skindex-29 and EORTC-QLQ-C30, and time to treatment failure.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
SCP32519702 · ATC
- Active substance
- Mogamulizumab
- Substance synonyms
- KW-0761, AMG 761
- Route of administration
- INTRAVENOUS
- Max daily dose
- 1.0 mg/kg milligram(s)/kilogram
- Max total dose
- 40 mg/Kg milligram(s)/kilogram
- Max treatment duration
- 18 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01XC25 — MOGAMULIZUMAB
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/16/1756
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- POTELIGEO is indicated for the treatment of adult patients with mycosis fungoides (MF) or Sézary syndrome (SS) who have received at least one prior systemic therapy.
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
European Organisation For Research And Treatment Of Cancer
- Sponsor organisation
- European Organisation For Research And Treatment Of Cancer
- Address
- Emmanuel Mounierlaan 83/11
- City
- Sint-Lambrechts-Woluwe
- Postcode
- 1200
- Country
- Belgium
Scientific contact point
- Organisation
- European Organisation For Research And Treatment Of Cancer
- Contact name
- Stéphanie Kromar
Public contact point
- Organisation
- European Organisation For Research And Treatment Of Cancer
- Contact name
- Vassilis Golfinopoulos
Third parties 6
| Organisation | City, country | Duties |
|---|---|---|
| Klinikos Limited ORG-100048116
|
Clydebank, United Kingdom | On site monitoring |
| Creapharm Clinical Supplies ORG-100020131
|
Le Haillan, France | Code 14 |
| Hospital Universitario 12 De Octubre ORG-100028548
|
Madrid, Spain | Laboratory analysis |
| Hospital Universitario Fundacion Jimenez Diaz ORG-100028994
|
Madrid, Spain | Laboratory analysis |
| Hospital Universitario Puerta De Hierro De Majadahonda ORG-100028532
|
Majadahonda, Spain | Laboratory analysis |
| Luxembourg Institute Of Health ORG-100028830
|
Dudelange, Luxembourg | Laboratory analysis |
Locations
6 EU/EEA countries · 11 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Denmark | Ongoing, recruiting | 3 | 1 |
| France | Ongoing, recruiting | 6 | 2 |
| Germany | Ongoing, recruiting | 10 | 3 |
| Greece | Ongoing, recruiting | 4 | 1 |
| Italy | Ongoing, recruiting | 6 | 2 |
| Spain | Ongoing, recruiting | 8 | 2 |
| Rest of world
United Kingdom
|
— | 6 | — |
Investigational sites
Copenhagen University Hospital
Oncology, Blegdamsvej 9, 2100, Copenhagen Oe
Assistance Publique Hopitaux De Paris
Dermatology, 1 Avenue Claude Vellefaux, 75010, Paris
Centre Hospitalier Universitaire De Bordeaux
Dermatology, 1 Rue Jean Burguet, 33000, Bordeaux
Universitaetsklinikum Mannheim GmbH
Dermatology, Venerology and Allergology, Theodor-Kutzer-Ufer 1-3, Wohlgelegen, Mannheim
Klinikum der Universitaet Muenchen AöR
Poliklinik für Dermatologie und Allergologie, Frauenlobstrasse 9-11, Ludwigsvorstadt-Isarvorstadt, Munich
Johannes Wesling Klinikum Minden
University Clinic for Dermatology, Venerology, Allergology, and Phlebology, Hans-Nolte-Strasse 1, Haeverstaedt, Minden
Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
Dermatology, Via Cherasco 15, 10126, Turin
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Hematology, Piazzale Spedali Civili 1, 25123, Brescia
Hospital Universitario 12 De Octubre
Dermatology, Bloque D, Avenida De Cordoba Sn, Madrid
Hospital Universitario Puerta De Hierro De Majadahonda
Radiation Oncology, Calle De Joaquin Rodrigo 2, 28222, Majadahonda
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Denmark | 2023-05-04 | 2023-07-25 | |||
| France | 2022-02-22 | 2023-06-20 | |||
| Germany | 2023-05-17 | 2023-10-25 | |||
| Greece | 2023-02-27 | 2023-03-07 | |||
| Italy | 2023-03-17 | 2023-11-17 | |||
| Spain | 2023-02-21 | 2023-05-09 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Temporary halts 1 · Art. 38 CTR
Temporary halt TH-56215
- Halt date
- 2024-10-30
- Member states concerned
- Germany
- Publication date
- 2024-11-07
- Reason
- Sponsor decision
- Explanation
- Two German sites currently authorized to recruit in the study (sites 414 and 527), have been performing CT scans instead of MRIs for baseline and disease assessments . At site Muehlenkreiskliniken Johannes Wesling Klinikum Minden: for seqIDs 10 (stage IIB, CT scans at baseline and FU week 32 disease assessment) and 11 (stage IIB, CT scan FU week 32 disease assessment); at site UniversitaetsMedizin Mannheim: for seqID 31 (stage IIB, CT scan at baseline) and seqID32 (stage IIB, CT scan at baseline). Please note that for patient 32 the method used for the baseline imaging assessment is not yet reported in the database.
Approvals of the initial submission were obtained under CTD on 23 November 2021 (Authorities) and 23 March 2022 (Ethics Committees).
Those approvals included the use of MRI instead of CT scan in the German sites.
Indeed, the EC requested the BfS approval for this study, but sites sent back the BfS statements confirming that BfS approval was not needed as they all agreed to use MRI instead of CT scan.
Subsequently, the sites of Prof Stadler (site 414) and Prof Nicolay (site 527) were authorized on 17 May 2023 and on 25 October 2023, respectively, both under the approved protocol v3.0 dd 28SEP2021 and the approved PISIC v3.0 dd 28SEP2021 and biobank PISIC v1.0 dd 13NOV2020.
Later, in November 2023, the first two patients were enrolled at site 414.
In the meantime, a subsequent substantial amendment (DE02 amendment) has been submitted with the protocol v3.1 dd 25NOV2022 and the PISIC v3.1 dd 25NOV2022 ) to align all EU countries with the same protocol and PISIC before the transition of the study to CTR.
During the DE02 review, the German EC realized that the previously approved German PISIC v3.0 dd 28SEP2021 and subsequent submitted PISIC v3.1 dd 25NOV2022 still contained the mention of CT scan despite the only permitted method for disease assessment in the MOGAT study in Germany was MRI following the initial CTD submission.
The PISIC has therefore been corrected but the first German patients enrolled in the study did sign a PISIC which mentions CT scan as one of the possible methods for disease assessment.
During a medical review of two patients at site 414, EORTC discovered that disease imaging assessments were conducted using CT scans instead of MRIs. Upon seeking clarification, the site Principal Investigator, Pr. Rudolf Stadler, confirmed that CT scans are considered the standard of care at his hospital for these assessments. It was understood that this German site acted in accordance with their standard practices by using CT scans, which resulted in no additional radiation exposure compared to what is typically involved in the diagnosis and follow-up of patients with this disease, thereby posing no harm to the patients enrolled in the trial.
Indeed, the initial disease stage for all patients enrolled in the trial by this study site was reported as IIB, for which staging and follow-up via CT scans are deemed standard practice according to current German AWMF guidelines for cutaneous lymphoma (Dippel et al., S2k-Leitlinie – Kutane Lymphome (ICD10 C82–C86): Update 2021, J Dtsch Dermatol Ges. 2022 Apr;20(4):537-555).
Meanwhile, a new stage IIB patient enrolled at site 527 also received a CT scan as part of the baseline disease assessment, despite previous reminders. Consequently, a temporary halt is being implemented to ensure that no new patients undergo CT scans, allowing sufficient time to fully understand the situation, including the circumstances at other open German sites. - Follow-up measures
- The patients still in the study will be followed as per protocol but again, sites should use MRI instead of CT scans and several reminders have been sent to the sites accordingly. As this imaging deviation is not impacting the safety of the current investigational treatment, patients still under treatment will continue their treatment as per protocol.
A teleconference will be held between sponsor and German sites in order to discuss in detail the temporary halt and the use of MRI vs CT scan. - Benefit-risk balance changed
- No
- Treatment stopped
- No
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 47 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_EL_EU CT 2022-502434-10-00_Redacted | 5.0 |
| Protocol (for publication) | D1_Protocol_EN_EU CT 2022-502434-10-00_Redacted | 5.0 |
| Protocol (for publication) | D4_QLQ-C30 questionnaire DE EU CT 2022-502434-10-00 | 3.0 |
| Protocol (for publication) | D4_QLQ-C30 questionnaire DK EU CT 2022-502434-10-00 | 3.0 |
| Protocol (for publication) | D4_QLQ-C30 questionnaire EL EU CT 2022-502434-10-00 | 3.0 |
| Protocol (for publication) | D4_QLQ-C30 questionnaire ES EU CT 2022-502434-10-00 | 3.0 |
| Protocol (for publication) | D4_QLQ-C30 questionnaire FR EU CT 2022-502434-10-00 | 3.0 |
| Protocol (for publication) | D4_QLQ-C30 questionnaire IT EU CT 2022-502434-10-00 | 3.0 |
| Protocol (for publication) | D4_Skindex29 questionnaire DE EU CT 2022-502434-10-00_redacted | 1.0 |
| Protocol (for publication) | D4_Skindex29 questionnaire DK EU CT 2022-502434-10-00_redacted | 1 |
| Protocol (for publication) | D4_Skindex29 questionnaire EL EU CT 2022-502434-10-00_redacted | 1 |
| Protocol (for publication) | D4_Skindex29 questionnaire ES EU CT 2022-502434-10-00_redacted | 1 |
| Protocol (for publication) | D4_Skindex29 questionnaire FR EU CT 2022-502434-10-00_redacted | 1 |
| Protocol (for publication) | D4_Skindex29 questionnaire IT EU CT 2022-502434-10-00_redacted | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 3.0 |
| Recruitment arrangements (for publication) | K1_recruitment arrangements | 2 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1.0 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1.0 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements FR | 1 |
| Subject information and informed consent form (for publication) | L1_GDPR notice | 5.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF | 5.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF | 5 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF | 5.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF | 5.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF | 5.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF | 4.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF | 5.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Addendum | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Addendum | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Biobank | 1.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF biobanking | 5.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_addendum | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_addendum | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_addendum | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_addendum | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_TC | 4.1 |
| Subject information and informed consent form (for publication) | L2_GP letter IT | 5.0 |
| Subject information and informed consent form (for publication) | L2_patient card mogamolizumab | 1.0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Poteligeo | 3.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_DA EU CT 2022-502434-10-00_redacted | 5.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_DE EU CT 2022-502434-10-00_redacted | 5.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_EL EU CT 2022-502434-10-00_redacted | 5.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_ES EU CT 2022-502434-10-00_redacted | 5.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_FR EU CT 2022-502434-10-00_redacted | 5.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_IT EU CT 2022-502434-10-00_redacted | 5.0 |
Application history
8 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-04-02 | Denmark | Acceptable 2024-04-30
|
2024-04-30 |
| 2 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-08-05 | Denmark | Acceptable 2024-11-07
|
2024-11-08 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-12-03 | Acceptable 2024-11-07
|
2024-12-03 | |
| 4 | SUBSTANTIAL MODIFICATION | SM-7 | 2025-02-04 | Denmark | Acceptable 2025-04-16
|
2025-04-16 |
| 5 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2025-06-06 | Acceptable 2025-04-16
|
2025-06-06 | |
| 6 | NON SUBSTANTIAL MODIFICATION | NSM-3 | 2025-06-25 | Acceptable 2025-04-16
|
2025-06-25 | |
| 7 | SUBSTANTIAL MODIFICATION | SM-8 | 2025-11-28 | Denmark | Acceptable 2026-02-12
|
2026-02-13 |
| 8 | SUBSTANTIAL MODIFICATION | SM-9 | 2026-04-03 | Acceptable | 2026-04-29 |