JOURNAL ONKOLOGIE – STUDIE

MOGAT

Anti-CCR4 Monoclonal Antibody (Mogamulizumab) and Total Skin Electron Beam Therapy (TSEB) in Patients With Stage IB-IIB Cutaneous T-Cell Lymphoma

Studien-Informationen Einschlusskriterien Studien-Rationale Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT04128072

Studienbeginn:
März 2023

Letztes Update:
05.04.2024

Wirkstoff:
Mogamulizumab, Mogamulizumab (subsequent cycles post TSEB)

Indikation (Clinical Trials):
Lymphoma, Lymphoma, T-Cell, Lymphoma, T-Cell, Peripheral, Lymphoma, T-Cell, Cutaneous

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
European Organisation for Research and Treatment of Cancer - EORTC

Collaborator:
-

Studienleiter

Pablo Luis Ortiz Romero
Principal Investigator
Hospital Universitario 12 De Octubre,Madrid, Spain

Richard Cowan
Principal Investigator
The Christie NHS Foundation Trust Manchester, UK

Jan Nicolay
Principal Investigator
UniversitaetsMedizin Mannheim, Mannheim, Germany

Kontakt

EORTC EORTC HQ
Kontakt:
Phone: +32 2 774 1611
E-Mail: eortc@eortc.org» Kontaktdaten anzeigen

Studienlocations
(3 von 13)

UniversitaetsMedizin Mannheim
68167 Mannheim
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps

Muehlenkreiskliniken Johannes Wesling Klinikum Minden
32429 Minden
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps

University Hospitals Copenhagen - Rigshospitalet
2100 Copenhagen
DenmarkRekrutierend» Google-Maps

CHU de Bordeaux - Groupe Hospitalier Saint-Andre - Hopital Saint-Andre
33075 Bordeaux
FranceRekrutierend» Google-Maps

Assistance Publique Hopitaux Paris- APHP Nord - Univ De Paris Cite - Hop. Saint Louis
75010 Paris
FranceRekrutierend» Google-Maps

Athens University - Attikon University General Hospital
12462 Athens
GreeceRekrutierend» Google-Maps

Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
25123 Brescia
ItalyRekrutierend» Google-Maps

Azienda Ospedaliera Città della Salute e della Scienza di Torino - Ospedale San Lazzaro
10126 Torino
ItalyRekrutierend» Google-Maps

Hospital De La Santa Creu I Sant Pau
08041 Barcelona
SpainRekrutierend» Google-Maps

Hospital Universitario 12 De Octubre
28041 Madrid
SpainRekrutierend» Google-Maps

Hospital Universitario Puerta De Hierro
28222 Madrid
SpainRekrutierend» Google-Maps

University Hospitals Birmingham NHS Foundation Trust (UHB) -Queen Elizabeth Medical Centre
B15 2TH Birmingham
United KingdomRekrutierend» Google-Maps

The Christie NHS Foundation Trust
M20 4BX Manchester
United KingdomRekrutierend» Google-Maps

Alle anzeigen

Studien-Informationen

Brief Summary:

Cutaneous T-Cell Lymphoma (CTCL) has a chronic, relapsing course with patients undergoing

multiple, consecutive therapies. Treatment aims at the clearance of skin disease,

minimization of recurrence, prevention of disease progression and preservation of quality of

life.

The treatment of CTCL is primarily determined by the disease extent. Prolonged complete

remissions have been obtained with skin-directed therapies in early stage Mycosis fungoides

(MF) (IA-IIA), whereas advanced stages CTCL (IIB-IVB) are often refractory to treatment and,

thus, have an unfavorable prognosis.

Currently, there is no standard treatment option for CTCL, especially for advanced stages,

and the optimal treatment sequence is still debated with a large variability in the

therapeutic approach across countries. Patients with advanced-stage disease or refractory

cutaneous CTCL should be treated with systemic therapies and, whenever possible, should be

offered to participate in clinical trials. Currently, there is a urgent call for new

treatments in CTCL with higher response rate and prolonged time to progression;

In this study, we propose a very innovative treatment schedule in which mogamulizumab is used

before Total Skin Electron Beam therapy (TSEB) for systemic disease control and as a

maintenance treatment after skin-directed therapy. We hypothesize that our regimen will show

a more manageable toxicity profile than a combination treatment and allow for a long-term

mogamulizumab administration.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Diagnosis of MF stage IB, IIA or IIB at registration, and MF stage should have never

met criteria for stage IIIA or higher.

- Subjects who have failed (refractory or relapsed) at least one prior course of

systemic therapy.

- All clinically significant toxic effects of prior cancer therapy to grade ≤ 1

according to the National Cancer Institute Common Terminology Criteria for Adverse

Events version 5.0 (NCI-CTCAE, v.5.0), excluding the specifications required in the

criteria 'Adequate haematological and organ function' below

- Males and female subjects ≥ 18 years

- WHO performance status 0-1

- Adequate haematological and organ function:

- absolute neutrophil count (ANC) ≥ 1.0 × 109/L

- platelets ≥ 75 × 109/L (≥ 75,000/mm3)

- bilirubin ≤ 1.5 × upper limit of normal (ULN) except for subjects with Gilbert's

syndrome;

- aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × ULN

- serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance > 50 mL/min using the

Cockcroft-Gault formula

- Subjects previously treated with anti-CD4 antibody or alemtuzumab are eligible

provided a washout period ≥ 3 months and CD4+ cell counts ≥ 200/mm3

- Clinically normal cardiac function based on 12-lead ECG and above the institutional

lower limit of normal for left ventricular ejection fraction assessed either by

multi-gated acquisition scan or cardiac ultrasound

- Women of child bearing potential (WOCBP) must have a negative serum pregnancy test

within 3 days prior to the first dose of study treatment

- WOCBP must agree to use effective contraception, defined as oral contraceptives,

double barrier method (condom plus spermicide or diaphragm plus spermicide) or

practice through abstinence from sexual intercourse during the study and for 6 months

after the last dose.

- Male subjects and their female partners of child bearing potential must be willing to

use an appropriate method of contraception defined as oral contraceptives, double

barrier method (condom plus spermicide or diaphragm plus spermicide) or practice

through abstinence from sexual intercourse (periodic abstinence, e.g., calendar,

ovulation, symptothermal, post-ovulation methods and withdrawal are not acceptable

methods of contraception) during the study and for 6 months after the last dose.

- Female subjects who are breast feeding should discontinue nursing prior to the first

dose of study treatment and until 6 months after the last study treatment

- Before patient registration, written informed consent must be given according to

ICH/GCP, and national/local regulations

Exclusion Criteria:

- Prior treatment with mogamulizumab, or any other anti-CCR4

- Prior TSEB

- Patients who received localised radiotherapy within 2 weeks prior to registration

- Patients who received any systemic therapy for MF within 4 weeks prior to

registration.

Note: In case of rapid progression, if patient has recovered from all toxicities AND last

dose occurred more than 5 half lives of the drug/treatment used, patient could be allowed

to start earlier after consultation with medical monitor

- History of other malignancy in the past 5 years with the exception of treated

carcinoma in situ of the cervix, localized prostate cancer with PSA <0.1, in-situ

melanoma, and non-melanoma skin cancer

- History of severe allergic anaphylactic reactions to chimeric, human or humanized

antibodies, or fusion proteins

- Known hypersensitivity to CHO cell products or any component of the mogamulizumab

formulation (see section 6.1.1)

- Significant uncontrolled intercurrent illness including, but not limited to:

- uncontrolled infection requiring antibiotics;

- clinically significant cardiac disease (class III or IV of the New York Heart

Association [NYHA] classification);

- unstable angina pectoris;

- angioplasty, stenting, or myocardial infarction within 6 months;

- clinically significant cardiac arrhythmia

- Have active sign of herpes zoster

- Patients with a history of autoimmune-related hypothyroidism who are on thyroid

replacement hormone are eligible for the study.

- Patients with eczema, psoriasis, lichen simplex chronicus, with dermatologic

manifestations only (e.g., patients with psoriatic arthritis are excluded) are

eligible for the study provided all of following conditions are met:

- Rash must cover <10% of body surface area

- Disease is well controlled at baseline and requires stable use of low to mild potency

topical corticosteroids for at least 4 weeks.

- No occurrence of acute exacerbations of the underlying condition requiring psoralen

plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral

calcineurin inhibitors, or high potency or oral corticosteroids within the previous 4

months.

- Immunomodulatory drugs or high-dose systemic steroids for concomitant or intercurrent

conditions other than T-cell lymphoma within 7 days of registration.

However, stable dose of a low dose systemic systemic corticosteroid (≤10 mg prednisone

equivalent per day) or stable dose of a low potency topical corticosteroid for at least 4

weeks prior to the registration is permitted. Subjects may receive intra-articular,

intraocular, inhalation or nasal corticosteroids. Initiation of treatment with

corticosteroids or increase in dose while on study is not permitted except for the

treatment of adverse events.

- Patients who are planned to receive stem cell transplantation

- Has a known history of Human T-lymphotropic virus 1 (HTLV-1), or human

immunodeficiency virus (HIV) (test to be performed within 21 days of registration if

allowed by local legislation)

- Has known active Hepatitis B or Hepatitis C

- Note: patient will be eligible if:

- Negative hepatitis B surface antigen (HBsAg) test at screening

- Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total

HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening . The

HBV DNA test will be performed only for patients who have a positive total HBcAb test.

- Has a history or current evidence of any condition, therapy, or laboratory abnormality

that might confound the results of the trial, interfere with the subject's

participation

- Any psychological, familial, sociological or geographical condition potentially

hampering compliance with the study protocol and follow-up schedule; those conditions

should be discussed with the patient before registration in the trial

Studien-Rationale

Primary outcome:

1. Progression Free Survival Rate at 48 weeks (Time Frame - Up to 48 weeks after start of mogamulizumab for each patient):
The primary endpoint is the progression free survival rate, assessed at 48 weeks after start of mogamulizumab

Secondary outcome:

1. Occurrence of Adverse Events (Time Frame - 48 months after last patient in)

2. Response rate 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

3. Progression-free survival (Time Frame - From the first patient treatment start till 48 weeks as of last patient in):
From start of mogamulizumab to the first date of progressive disease or death from any cause

4. Overall survival (Time Frame - From the first patient treatment start till 5 years after last patient treatment):
Start of mogamulizumab till the date of death from any cause

5. Time to progression (Time Frame - From the first patient treatment start till 48 weeks as of last patient in):
From start of mogamulizumab to the date of first documentation of progressive disease or death due to progressive disease, whichever occurs first

6. Duration of response (Time Frame - From the first patient treatment start till 48 weeks as of last patient in):
Duration of response will be measured for patients achieving a partial response or complete response are first met until the first date that recurrent or progressive disease

7. Time to next treatment (Time Frame - From the first patient treatment start till 48 weeks as of last patient in):
From time from initiation of mogamulizumab until the time the initiation of any total skin-equivalent treatment (topical treatment to >50% of body surface, phototherapy, second TSEB) or systemic treatment is recorded

Geprüfte Regime

Mogamulizumab:
• Patients will receive mogamulizumab 1.0 mg/kg IV over at least 1 hour on Days 1, 8, 15 and 22 of the first 28 day treatment cycle (C1) and on Days 1 and 15 of subsequent 28 day cycle (C2).
Total Skin Electron Beam Therapy (TSEB):
After completion of C2, patients will be administered TSEB at a dose of 12 Gy in 8 fractions (4 fractions per week). TSEB will start 28 days (window of + 7 days) after mogamulizumab (C2 D1). In case of toxicity from mogamulizumab, the maximum delay permitted for the start of TSEB is 2 weeks. If recovery to at least grade 1 from toxicity exceeds the 2 weeks interval, please contact the medical monitor. Mogamulizumab is stopped during TSEB administration.
Mogamulizumab (subsequent cycles post TSEB):
• Mogamulizumab will be restarted at a dose of 1.0 mg/kg IV on Days 1, 8, 15 and 22 for cycle 3. Subsequent cycles will be administered as for C2. Treatment with mogamulizumab will be continued until disease progression (PD) or the occurrence of another withdrawal criterion.

Quelle: ClinicalTrials.gov

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