Mittwoch, 8. Mai 2024
Navigation öffnen
Anzeige:
Wefra Programatic
 
JOURNAL ONKOLOGIE – STUDIE
MorningLyte

Study of Mosunetuzumab Plus Lenalidomide Compared to Anti-CD20 Anti-body + Chemotherapy in Follicular Lymphoma FLIPI2-5

Noch nicht rekrutierend

NCT-Nummer:
NCT06284122

Studienbeginn:
April 2024

Letztes Update:
15.03.2024

Wirkstoff:
Mosunetuzumab, Lenalidomide, Rituximab, Obinutuzumab, Cyclophosphamide, Doxorubicin, Vincristin, Prednisone, Bendamustin

Indikation (Clinical Trials):
Lymphoma, Lymphoma, Follicular

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
The Lymphoma Academic Research Organisation

Collaborator:
Lymphoma Study Association, Swiss Group for Clinical Cancer Research, Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea,

Studienleiter

Franck MORSCHHAUSER
Principal Investigator
Lymphoma Study Association
Christian BUSKE
Principal Investigator
GLA

Kontakt

Studienlocations
(3 von 49)

CHU DE BORDEAUX - HOPITAL HAUT-LEVEQUE - CENTRE FRANCOIS MAGENDIE - Service d'Hématologie et Thérapie Cellulaire
33604 Pessac
France» Google-Maps
Ansprechpartner:
François-Xavier GROS, MD» Ansprechpartner anzeigen
CENTRE HENRI BECQUEREL - Service Hématologie
76038 Rouen
France» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

This study is a phase III, randomized, open-label, international, multicenter, interventional

trial, designed to compare the efficacy and safety of mosunetuzumab in combination with

lenalidomide versus anti-CD20 monoclonal antibody (mAb) plus chemotherapy in patients with

previously untreated Follicular Lymphoma International Prognostic Index (FLIPI) 2-5

follicular lymphoma This study is composed of a screening period (up to 6 weeks before

randomization, i.e., 42 days), a treatment period (30 months i.e., 125w), a safety follow-up

period (90 days i.e., 3 months), and a survival follow-up period (up to 7 years after the

last randomized patient). The enrollment will last approximately 34 months. The total

duration of the study will be therefore approximately 10 years.

Once a patient provides written consent, they may enter the screening phase, with a duration

up to 6 weeks prior to randomization and initiation of treatment.

Upon completion of the required assessments in the screening phase, and fulfillment of the

eligibility criteria, patients will be randomized. Investigators will be requested to

indicate their treatment choice among permitted immuno-chemotherapy regimens just before

randomization.

The treatment period for each patient starts with the first intake. The patients will receive

protocol-specified treatments until:

- inability to achieve a response at the end of induction phase (at M12 evaluation for

experimental arm, and at M6 evaluation for control arms),

- relapse or progression of the disease,

- withdrawal of consent,

- or unacceptable toxicity

In the experimental arm, patients will be treated for 1 cycle of 3 weeks for mosunetuzumab

and then 11 cycles of 4 weeks for mosunetuzumab and lenalidomide (47 weeks, around 11 months)

during the induction phase, and for a maximum of 9 additional cycles of 8 weeks during the

maintenance phase (72 weeks, around 17 months), up to around 125 weeks (30 months). Patients

should start the maintenance phase 7 to 8 weeks after the start of last induction cycle

(C12).

In the control arm, patients will be treated for 8 or 6 cycles of 3 or 4 weeks for anti-CD20

mAb +cyclophosphamide-doxorubicine-vincristine-prednisone (CHOP) or anti-CD20 mAb +

Bendamustine, respectively, depending on the assigned arm (24 weeks, around 5 months) during

the induction phase, and for a maximum of 12 additional cycles of 8 weeks during the

maintenance phase (96 weeks, around 22 months), up to around 125 weeks (30 months). Patients

should start the maintenance phase, 6 to 7 or 7 to 8 weeks after the start of last induction

cycle (C8 or C6).

The option to cross-over from the control arm to the experimental arm is not allowed.

All randomized patients will be followed for progression-free survival and overall survival

using the same schedule. Patients will be followed up from End of treatment evaluation every

3 months during the first two years, then every 6 months during the next 3 years, then yearly

until the end of study.

The end of study will occur when all randomized patients have been followed-up for survival

for at least 7 years (or discontinued study early).

Ein-/Ausschlusskriterien

Inclusion Criteria:

1. Patient with histologically proven previously untreated CD20+ follicular lymphoma

grade 1, 2, or 3a (including patient watched during up to 10 years after initial

diagnosis) as assessed by the investigators according to the World Health Organization

(WHO) 2016 classification12, or classical follicular lymphoma according to the WHO

2022 classification13. Diagnostic tissue must be available for central pathology

review, exploratory endpoints and secondary data use. (Patients with absolute

lymphocyte count > 20 G/L must be discussed with the Sponsor before

screening/inclusion).

2. FLIPI 2-5.

3. All Ann Arbor stages (including stage I if FLIPI ≥ 2).

4. Must need treatment as evidenced by at least one of the following criteria:

- Bulky disease defined as:

- a nodal or extranodal mass/lesion > 7 cm in its largest diameter or,

- involvement of at least 3 nodal or extranodal sites (each with a diameter greater

than > 3 cm)

- Presence of at least one of the following B symptoms:

- fever (> 38°C) of unclear etiology

- night sweats

- weight loss greater than 10% within the prior 6 months

- Symptomatic splenomegaly

- Any compressive syndrome (for example, but not restricted to- ureteral, orbital,

gastrointestinal)

- Any one of the following cytopenias due to lymphoma:

- hemoglobin < 10g/dL (6.25 mmol/L)

- platelets <100 x 109/L, or

- absolute neutrophil count (ANC) < 1.5 x 109/L

- Pleural or peritoneal serous effusion (irrespective of cell content)

- β2microglobulin > ULN or lactate dehydrogenase (LDH) > ULN

5. At least one bi-dimensionally measurable nodal lesion, defined as > 1.5 cm in its

longest dimension, or at least one bi-dimensionally measurable extra nodal lesion,

defined as > 1.0 cm in its longest dimension (and 18F-2-fluoro-2-deoxy-D-glucose

(FDG)-avid lesion).

6. Patient who understood and voluntarily signed and dated an informed consent prior to

any study-specific assessments/procedures.

7. Must be ≥ 18 years at the time of signing the informed consent form (ICF).

8. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.

9. Estimated minimum life expectancy of 3 months.

10. Adequate hematological function within 28 days prior to signing informed consent,

including:

- Absolute neutrophil count (ANC) ≥ 1 x 109/L

- Platelet count ≥ 75 x 109/L, or ≥ 30 x 109/L if bone marrow infiltration or

splenomegaly

- Hemoglobin ≥ 8.0 g/dL (5 mmol/L) unless related to bone marrow infiltration or

splenomegaly. Transfusion is allowed before starting treatment (no required

window)

11. Normal laboratory values:

- Measured or estimated creatinine clearance ≥ 40 mL/min calculated by

institutional standard method (MDRD or Cockcroft-Gault)

- aspartate aminotransferase (AST) or alanine aminotransférase (ALT) ≤ 2.5 x the

upper limit of normal (ULN), except in patients with documented liver or

pancreatic involvement by lymphoma ≤ 5 x ULN

- Serum total bilirubin ≤ 1.5 x ULN (or ≤ 3 x ULN for patients with Gilbert

syndrome), except in patients with documented liver or pancreatic involvement by

lymphoma ≤ 3 x ULN

12. left ventricular ejection fraction (LVEF) within normal range (i.e. > 50% as evaluated

by Transthoracic Echocardiography or > 45% as evaluated by isotopic method (MUGA

scan)).

13. Patients should be able to receive adequate prophylaxis and/or therapy for

thromboembolic events (aspirin, low molecular weight heparin or direct oral

anticoagulants).

Patients with a curative anticoagulation therapy can be enrolled. A patient with deep

vein thrombosis due to compressive syndrome is eligible if a curative anticoagulation

therapy has been started at least 1 week before initiating study treatment: low

molecular weight heparin possible at treatment onset, then direct oral anticoagulants

according to local practices.

14. Must be able to adhere to the study visit schedule and other protocol requirements.

15. Negative SARS-CoV-2 test within 7 days prior to randomization. Rapid antigen test is

also acceptable. If a patient has a positive SARS-CoV-2 test before randomization,

another test should be done and be negative within 7 days before initiation of

treatment.

16. Negative HIV test before randomization, with the following exception:

Patients with a positive HIV test before randomization are eligible provided they are

stable on antiretroviral therapy for at least 4 weeks, have a CD4 count ≥ 200/ µL,

have an undetectable viral load, and have not had a history of opportunistic infection

attributable to AIDS within the last 12 months.

17. For women of childbearing potential (WOCBP) (refer to section 14.7): must have a

negative result for pregnancy test (highly sensitive serum) at screening and within 7

days before initiation of study treatment, and agree to abstain from breastfeeding

during study participation, and for at least 28 days after the final dose of

lenalidomide (if applicable), 3 months after the final dose of mosunetuzumab and

tocilizumab (if applicable), 6 months after the final dose of chemotherapies (if

applicable), 12 months after the final dose of rituximab (if applicable), and 18

months after the final dose of obinutuzumab (if applicable).

18. For men (refer to section 14.7): Agreement to remain abstinent (refrain from

heterosexual intercourse) or use a condom, and agreement to refrain from donating

sperm, as defined below: with a female partner of childbearing potential or pregnant

female partner, men must remain abstinent or use a condom during the treatment period

(including periods of treatment interruption), and for at least 28 days after the

final dose of lenalidomide (if applicable), 2 months after the final dose of

tocilizumab (if applicable), 6 months after the final dose of chemotherapies (if

applicable), 12 months after the final dose of rituximab (if applicable), and 3 months

after the final dose of obinutuzumab (if applicable).

19. Patient covered by any social security system (France).

20. Patient who understands and speaks one of the country official languages, unless local

regulation authorizes independent translators.

Exclusion Criteria:

1. Grade 3b follicular lymphoma according to the WHO 2016 classification12, or follicular

large B-cell lymphoma according to the WHO 2022 classification13.

2. Suspicion or clinical evidence of transformed lymphoma at enrollment by investigator

assessment (e.g., high SUV in at least one lesion that was not biopsied, and

discordant with SUV of biopsied lesion (at least double of the average SUV), LDH > 2.5

x ULN especially in a context of rapidly progressive disease, etc. (Please contact the

Sponsor to discuss any possible inclusion in borderline cases or any doubt)

3. Prior localized radiotherapy for the FL.

4. Prior history of another lymphoma.

5. Uncontrolled symptomatic pleural or serous effusion requiring urgent treatment within

48 hours (patients with controlled disease after adequate pleural/serous drainage

and/or effective pleurX™ or similar system are eligible).

6. Uncontrolled symptomatic ureterohydronephrosis resulting in renal failure (patients

with adequate management i.e. ureteral catheter or double J stent allowing renal

failure control are eligible).

7. Symptomatic lymphomatous epidural lesion (patients whose disease is controlled by

neurosurgery or short course of steroids are eligible).

8. Use of any standard or experimental anti-cancer drug therapy within 42 days of the

start (Day 1) of study treatment.

9. Systemic immunosuppressive medications (including, but not limited to,

cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis

factor agents) or corticosteroid > 1mg/kg/day prednisone or equivalent within 10 days

prior to first dose of study treatment. Systemic corticosteroid treatment < 20 mg/day

of prednisone or equivalent, inhaled corticosteroids and mineralocorticoids for

management of orthostatic hypotension is permitted. A single dose of dexamethasone for

nausea or B symptoms is permitted.

10. Received a live, attenuated vaccine within 4 weeks before the first dose of study

treatment, or in whom it is anticipated that such a live attenuated vaccine will be

required during the study period or within 5 months after the final dose of study

treatment.

11. Major surgery (excluding surgical documentation of FL) within 28 days prior to signing

informed consent.

12. Seropositive for or active viral infection with Hepatitis B virus (HBV):

- HBsAg positive

- HBsAg negative, anti-HBs positive and/or anti-HBc positive and detectable viral

DNA (Patients who are HBsAg negative, anti-HBs positive and/or anti-HBc positive

but viral DNA negative are eligible. They should be treated and perform testing

at regular interval; Patients who are seropositive due to a history of hepatitis

B vaccine (anti-HBs positive) are eligible).

13. Known seropositive for, or active infection hepatitis C virus (HCV) (Patients who are

positive for HCV antibody with a negative viral RNA are eligible).

14. Known or suspected hypersensitivity to biopharmaceuticals produced in Chinese hamster

ovarian (CHO) cells or any component of the mosunetuzumab, Anti-CD20 mAb, tocilizumab,

lenalidomide formulation, including mannitol; or to any of the excipients.

15. History of solid organ transplantation or allogeneic stem cell transplant (SCT).

16. Active autoimmune disease requiring treatment.

17. History of autoimmune disease, including, but not limited to, myasthenia gravis,

myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis,

inflammatory bowel disease, vascular thrombosis associated with antiphospholipid

syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, multiple

sclerosis, vasculitis, or glomerulonephritis

- Participants with a history of autoimmune-related hypothyroidism on a stable dose

of thyroid replacement hormone may be eligible.

- Participants with controlled Type 1 diabetes mellitus who are on an insulin

regimen are eligible for the study.

- Participants with a history of disease-related immune thrombocytopenic purpura or

autoimmune hemolytic anemia may be eligible.

- Participants with a remote history of, or well-controlled autoimmune disease,

with a treatment-free interval from immunosuppressive therapy for 12 months may

be eligible after review and discussion with the Primary investigator.

18. Participants with any active infection such as known active bacterial, viral

(including SARS-CoV-2), fungal, mycobacterial, parasitic, or other infection

(excluding fungal infections of nail beds), known or suspected chronic active

Epstein-Barr virus (EBV) infection, are excluded.

19. Evidence of any significant, concomitant disease that could affect compliance with the

protocol or interpretation of results, including, but not limited to:

- significant cardiovascular disease [e.g., Objective Class C or D heart diseases

(cf. Classes of Heart Failure | American Heart Association), myocardial

infarction within the previous 6 months, unstable arrhythmia, or unstable angina)

- significant pulmonary disease (such as obstructive pulmonary disease or history

of bronchospasm)

- clinically significant history of liver disease, including viral or other

hepatitis, or cirrhosis

- current or past history of central nervous system (CNS) disease, such as stroke,

epilepsy, CNS vasculitis, or neurodegenerative disease. Participants with a

history of stroke who have not experienced a stroke or transient ischemic attack

in the past 1 year and have no residual neurologic deficits as judged by the

investigator are allowed. Participants with a history of epilepsy who have had no

seizures in the past 2 years with or without anti-epileptic medications can be

eligible.

20. History of confirmed progressive multifocal leukoencephalopathy (PML).

21. Known or suspected history of hemophagocytic lymphohistiocytosis (HLH).

22. History of erythema multiforme, Grade ≥3 rash, or blistering rash following prior

treatment with immunomodulatory derivatives.

23. History of interstitial lung disease (ILD), drug-induced pneumonitis, and autoimmune

pneumonitis.

24. Active malignancy other than the one treated in this research. Prior history of

malignancies unless the patient has been free of the disease for ≥ 3 years. However,

patients with the following history/concurrent conditions are eligible:

- Localized non-melanoma skin cancer.

- Carcinoma in situ of the cervix.

- Carcinoma in situ of the breast.

- Incidental histologic finding of prostate cancer (T1a or T1b as per Tumor Node

Metastasis (TNM) staging system) or prostate cancer that has been treated with

curative intent.

25. Presence or history of CNS or meningeal involvement by lymphoma.

26. Pregnant, planning to become pregnant or lactating WOCBP.

27. Any significant medical conditions, including the presence of laboratory abnormality

or psychiatric illness which places the patient at unacceptable risk if he/she were to

participate in the study, and likely to interfere with participation in this clinical

study (according to the investigator's decision) or which confounds the ability to

interpret data from the study.

28. Person deprived of his/her liberty by a judicial or administrative decision.

29. Person hospitalized without consent.

30. Adult person under legal protection.

Nota bene: for 28., if there is an individual benefit for such patients, an Ethics

Committee will have to be informed case by case.

Studien-Rationale

Primary outcome:

1. Progression Free Survival (PFS) (Time Frame - 130 PFS events assessed by an Independent Review Committee (IRC) (4.6 years)):
time from randomization to the date of first documented disease progression/relapse or death from any cause, by Lugano 2014

2. Progression Free Survival (PFS) (Time Frame - 173 PFS events assessed by IRC (5.8 y)):
time from randomization to the date of first documented disease progression/relapse or death from any cause, by Lugano 2014

Secondary outcome:

1. Overall Response (OR) (Time Frame - 6 months):
by Lugano 2014, assessed by investigator and IRC

2. Complete Metabolic Rate (CMR) (Time Frame - 6 months):
by Lugano 2014, assessed by investigator and IRC

3. Overall Response (OR) (Time Frame - 12 months):
by Lugano 2014, assessed by investigator and IRC

4. Complete Metabolic Rate (CMR) (Time Frame - 12 months):
by Lugano 2014, assessed by investigator and IRC

5. Best Overall Response (CMR + PMR) rate (Time Frame - 4.6 years):
by Lugano 2014, assessed by investigator and IRC

6. Best Overall Response (CMR + PMR) rate (Time Frame - 5.8 years):
by Lugano 2014, assessed by investigator and IRC

7. Progression of disease within 2 years (POD24) (Time Frame - 2 years):
rate of progression of disease (POD) within 2 years of first line therapy

8. PFS (Time Frame - 4.6 years):
by Lugano 2014, assessed by investigator

9. PFS (Time Frame - 5.8 years):
by Lugano 2014, assessed by investigator

10. Event Free Survival (EFS) by Lugano 2014 (Time Frame - 4.6 years):
time between randomization and date of first documented disease progression/relapse, initiation of a new anti-lymphoma treatment or death from any cause

11. Event Free Survival (EFS) by Lugano 2014 (Time Frame - 5.8 years):
time between randomization and date of first documented disease progression/relapse, initiation of a new anti-lymphoma treatment or death from any cause

12. Time to Next Anti-Lymphoma Treatment (TTNLT) (Time Frame - 4.6 years):
time between randomization and date of first documented administration of any new anti-lymphoma treatment

13. Time to Next Anti-Lymphoma Treatment (TTNLT) (Time Frame - 5.8 years):
time between randomization and date of first documented administration of any new anti-lymphoma treatment

14. Duration of response (Time Frame - 4.6 years):
defined for patients with a best overall response of CMR or PMR determined by Lugano 2014, defined as the time of 1st occurrence of CMR or PMR to disease progression/relapse or death from any cause

15. Duration of response (Time Frame - 5.8 years):
defined for patients with a best overall response of CMR or PMR determined by Lugano 2014, defined as the time of 1st occurrence of CMR or PMR to disease progression/relapse or death from any cause

16. Overall Response (OR) (Time Frame - End of treatment (12 months for experimental arm, 6 months for comparative arms)):
assessed by investigator and IRC

17. Complete Metabolic Rate (CMR) (Time Frame - End of treatment (12 months for experimental arm, 6 months for comparative arms)):
assessed by investigator and IRC

18. Duration of complete response (Time Frame - 4.6 years):
for patients with a best overall response of CMR determined by Lugano 2014, define as the time of first occurrence of CMR to disease progression/relapse or death from any cause

19. Duration of complete response (Time Frame - 5.8 years):
for patients with a best overall response of CMR determined by Lugano 2014, define as the time of first occurrence of CMR to disease progression/relapse or death from any cause

20. Overall Survival (OS) (Time Frame - 4.6 years):
time from randomization to death from any cause

21. Overall Survival (OS) (Time Frame - 5.8 years):
time from randomization to death from any cause

22. Incidence and severity of Adverse Events (AE) including Serious and Special Interest AE (SAEs and AESIs) (Time Frame - 4.6 years)

23. Incidence and severity of AEs including SAEs and AESIs (Time Frame - 5.8 years)

24. Tolerability, as assessed by incidence of dose interruptions, delays, dose reductions, and study treatment discontinuation (Time Frame - 4.6 years)

25. Tolerability, as assessed by incidence of dose interruptions, delays, dose reductions, and study treatment discontinuation (Time Frame - 5.8 years)

26. Incidence of Second Primary Malignancies (SPM) (Time Frame - 4.6 years)

27. Incidence of Second Primary Malignancies (SPM) (Time Frame - 5.8 years)

28. anti-drug antibodies (ADA) to mosunetuzumab (Time Frame - each cycle, 18 months, 24 months, 30 months)

29. Time to deterioration in physical functioning (Time Frame - baseline, 6 months, 12 months, 18 months, 24 months, 30 months or end of treatment):
EORTC QLQ-C30 quality of life questionnaire

30. Time to deterioration in lymphoma symptoms (Time Frame - baseline, 6 months, 12 months, 18 months, 24 months, 30 months or end of treatment):
FACTLym LYMS quality of life questionnaire

31. Maximum serum concentration of mosunetuzumab - Cmax (Time Frame - each cycle, 18 months, 24 months, 30 months)

32. Minimum serum concentration of mosunetuzumab - Cmin (Time Frame - each cycle, 18 months, 24 months, 30 months)

33. Area under the curve of serum concentration of mosunetuzumab - AUC (Time Frame - each cycle, 18 months, 24 months, 30 months)

34. Maximum serum concentration of lenalidomide - Cmax (Time Frame - each cycle, 18 months, 24 months, 30 months)

35. Minimum serum concentration of lenalidomide - Cmin (Time Frame - each cycle, 18 months, 24 months, 30 months)

36. Area under the curve of serum concentration of lenalidomide - AUC (Time Frame - each cycle, 18 months, 24 months, 30 months)

Studien-Arme

  • Experimental: Mosun-Len
    Mosunetuzumab + lenalidomide
  • Active Comparator: R-CHOP
    Rituximab-CHOP
  • Active Comparator: G-CHOP
    Obinutuzumab-CHOP
  • Active Comparator: R-Benda
    Rituximab-Bendamustin
  • Active Comparator: G-Benda
    Obinutuzumab-Bendamustin

Geprüfte Regime

  • Mosunetuzumab:
    5 mg (step-up dosing) Day 1 of C1 45 mg Day 8 and Day 15 of C1, 45 mg Day 1 from C2 to C12, 45 mg Day 1 from C13 to C21
  • Lenalidomide:
    20 mg/day Day 1 to Day 21 from C2 to C12
  • Rituximab:
    when associated to CHOP IV 375mg/m² SC 1400 mg allowed from C2 Day 1 of C1 Day 1 from C2 to C6 Day 1 from C7 to C20
  • Obinutuzumab:
    when associated to CHOP 1000 mg Day 1, Day 8, Day 15 of C1 Day 1 from C2 to C8 Day 1 from C9 to C18
  • Cyclophosphamide:
    750 mg/m2 Day 1 from C1 to C6
  • Doxorubicin:
    50 mg/m2 Day 1 from C1 to C6
  • Vincristin:
    1.4 mg/m2 (cap cf. below)$ Day 1 from C1 to C6
  • Prednisone:
    100 mg/day Day 1 to Day 5 from C1 to C6
  • Rituximab:
    when associated to bendamustin IV 375mg/m² SC 1400 mg allowed from C2 Day 1 of C1 Day 1 from C2 to C6 Day 1 from C7 to C18
  • Obinutuzumab:
    when associated to bendamustin 1000 mg Day 1, Day 8, Day 15 of C1 Day 1 from C2 to C8 Day 1 from C9 to C20
  • Bendamustin:
    90 mg/m2 Day 1 and Day 2 from C1 to C6

Quelle: ClinicalTrials.gov


Sie können folgenden Inhalt einem Kollegen empfehlen:

"Study of Mosunetuzumab Plus Lenalidomide Compared to Anti-CD20 Anti-body + Chemotherapy in Follicular Lymphoma FLIPI2-5"

Bitte tragen Sie auch die Absenderdaten vollständig ein, damit Sie der Empfänger erkennen kann.

Die mit (*) gekennzeichneten Angaben müssen eingetragen werden!

Die Verwendung Ihrer Daten für den Newsletter können Sie jederzeit mit Wirkung für die Zukunft gegenüber der MedtriX GmbH - Geschäftsbereich rs media widersprechen ohne dass Kosten entstehen. Nutzen Sie hierfür etwaige Abmeldelinks im Newsletter oder schreiben Sie eine E-Mail an: rgb-info[at]medtrix.group.