Trial assessing atezolizumab (anti-PD-L1) as treatment option for patients with mycosis fungoides/sezary syndrome having progressed under or after previous therapy

• Register: EUCTR
• Last refreshed on: 13 October 2020
• Main ID: EUCTR2017-003680-35-GB
• Date of registration: 01/05/2018
• Prospective Registration: Yes
• Primary sponsor: European Organisation for Research and Treatment of Cancer (EORTC)
• Public title: Trial assessing atezolizumab (anti-PD-L1) as treatment option for patients with mycosis fungoides/sezary syndrome having progressed under or after previous therapy
• Scientific title: Phase II trial of atezolizumab (anti-PD-L1) in the treatment of stage IIb-IV mycosis fungoides/sezary syndrome patients relapsed/refractory after a previous systemic treatment (PARCT) - PARCT
• Date of first enrolment: 31/01/2019
• Target sample size: 26
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-003680-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: yes; Other trial design description: Single arm; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, France, Germany, Greece, Italy, Netherlands, Spain, Switzerland, United Kingdom

Contacts

• Name: Regulatory Affairs Department
• Affiliation: European Organisation for Research and Treatment of Cancer (EORTC)

• Name: Regulatory Affairs Department
• Affiliation: European Organisation for Research and Treatment of Cancer (EORTC)

Key inclusion & exclusion criteria

Inclusion criteria:
-Male or female patients with diagnosis of CTCL (mycosis fungoides or Sézary-Syndrome) tumor stage IIB to IVB (Ref. 12)
-Availability of tumor sample for evaluation of PD-L1 expression. A 4-mm formalin-fixed punch biopsy is recommended.
-Inadequate response or secondary treatment failure to at least 1 prior systemic therapy for CTCL according to treatment guidelines (e.g. INF-2a or bexarotene).
? Age = 18 years old
? WHO performance status 0-1
? Adequate bone marrow and organ function prior to receiving the first dose of study treatment:
? Hemoglobin > 10.0 g/dL (> 100 g/L) or hematocrit > 30% (> 0.30 v/v);
? White blood cell count > 3.0 x 10E9/L (> 3000/mmE3);
? Absolute neutrophil count of > 1.5 x 10E9/L (> 1500/mmE3);
? Platelet count > 100 x 10E9/L (> 100,000/mmE3);
? Estimated creatinine clearance > 40 mL/min based on the Cockcroft Gault calculation or serum creatinine less than 1.5 times the upper limit of normal (ULN)
? Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) values less than 2 times the upper limit of normal (ULN)
? Serum total bilirubin = 1.5 x ULN
? Patients with suspicion of Gilbert disease who have serum bilirubin level =3 x ULN may be enrolled.
-Clinically normal cardiac function based on 12 lead ECG without clinically relevant abnormalities and the institutional lower limit of normal for left ventricular ejection fraction as assessed either by multi-gated acquisition scan or cardiac ultrasound.
-Women of child bearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours prior to the first dose of study treatment.
Note: women of childbearing potential are defined as premenopausal females capable of becoming pregnant (i.e. females who have had any evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy). However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior
chemotherapy, antiestrogens, low body weight, ovarian suppression or other reasons.
-Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 5 months after the last dose of treatment. A highly effective method of birth control is defined as a method which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly. Such methods include:
? Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
? Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
? Intrauterine device (IUD)
? Intrauterine hormone-releasing system (IUS)
? Bilateral tubal occlusion
? Vasectomized partner
? Sexual abstinence (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient)
-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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age ran
Exclusion criteria:
-Patients for whom only local therapy is indicated
-Received chemotherapy or targeted small molecule therapy within 4 weeks prior to registration
-Persistence of clinically relevant therapy-related toxicity from previous systemic treatment. Grade 1 or 2 adverse events (AEs) are acceptable.
-Received a T cell depleting antibody (e.g. Alemtuzumab) within 3 months prior to registration.
-Prior therapy with anti-PD1, anti-PD-L1, anti-PD-L2.
-History of other malignancy in the past 5 years with the exception of treated carcinoma in situ of the cervix and non-metastatic, non-melanoma skin cancer.
-Patients with known central nervous system (CNS) involvement with lymphoma.
-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 atezolizumab formulation.
-History of any of the following cardiovascular conditions within 6 months prior to registration:
Unstable angina.
? Clinically significant cardiac arrhythmias.
? Myocardial infarction.
-Have current or recent (past 6 months) history of severe, progressive, or uncontrolled renal, hepatic, gastrointestinal, metabolic, endocrine, pulmonary, cardiovascular, or neurological disease.
-Severe infection within 4 weeks prior to registration, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
-Have active signs of disseminated herpes zoster or disseminated herpes simplex, or a recurrent (more than one episode of) localized, dermatomal herpes zoster.
-Administration of a live, attenuated vaccine within 4 weeks prior to Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study. Any live, attenuated vaccine (e.g. FluMist®) is prohibited while the patient is receiving atezolizumab and for a period of 90 days after discontinuation of atezolizumab. Inactivated influenza vaccines are allowed only during flu season.
-Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:
? Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
? Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
? Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo 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 only low-potency topical corticosteroids
-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 12months
-Has a known history of HIV (test to be performed within 21 days of registration)
-Has known active Hepatitis B or Hepatitis C.
-Note: patient will be eligible if Negative hepatitis B surface antigen (HBsAg) test at screening
-Negative

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Subtypes of Cutaneous T cell ltymphoma (CTCL): Mycosis Fungoides (MF) and Sézary Syndrome (SS)
MedDRA version: 22.0 Level: LLT Classification code 10028508 Term: Mycosis fungoides/Sezary syndrome System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 22.0 Level: LLT Classification code 10028483 Term: Mycosis fungoides System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0 Level: HLT Classification code 10028484 Term: Mycoses fungoides System Organ Class: 10005329 - Blood and lymphatic system disorders
MedDRA version: 20.0 Level: HLGT Classification code 10025321 Term: Lymphomas non-Hodgkin's T-cell System Organ Class: 10005329 - Blood and lymphatic system disorders
MedDRA version: 20.0 Level: SOC Classification code 10005329 Term: Blood and lymphatic system disorders System Organ Class: 10005329 - Blood and lymphatic system disorders
MedDRA version: 20.0 Level: SOC Classification code 10029104 Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps) System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0 Level: HLT Classification code 10042356 Term: Skin and subcutaneous conditions NEC System Organ Class: 10040785 - Skin and subcutaneous tissue disorders
MedDRA version: 20.0 Level: HLGT Classification code 10040790 Term: Skin and subcutaneous tissue disorders NEC System Organ Class: 10040785 - Skin and subcutaneous tissue disorders
MedDRA version: 20.0 Level: SOC Classification code 10040785 Term: Skin and subcutaneous tissue disorders System Organ Class: 10040785 - Skin and subcutaneous tissue disorders

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: Tecentriq
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: ATEZOLIZUMAB
CAS Number: 1380723-44-3
Current Sponsor code: MPDL3280A
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-

Primary Outcome(s)

Primary end point(s): Best overall response (CR+PR) rate (EORTC-ISCL-USCLC criteria), observed up to maximum of 1 year from patient registration.

Timepoint(s) of evaluation of this end point: ORR is counted from patient registration up to a maximum of 1 year of treatment

Main Objective: To determine the antitumor activity of atezolizumab for patients with refractory
or relapsed advanced stages of mycosis fungoides and Sézary syndrome, assessed in terms of the overall response rate, according to EORTC-ISCL-USCLC criteria

Secondary Objective: Not applicable

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: o PFS is counted from the date of treatment start to the first date of progressive disease or death from any cause.
o OS is counted from the date of treatment start to the date of death from any cause.
o Time to response (CR/PR) is counted from the date of treatment start until the time measurement criteria for CR/PR (whichever is first recorded) are first met.
o Duration of response is counted from the date when criteria for CR/PR are first met till disease progression
o Time to next systemic treatment is counted as time from the end of the current atezolizumab treatment until the time the next systemic treatment is recorded.
o Evaluate safety and tolerability in this patient population is counted from patient registration until 3 months after treatment discontinuation

Secondary end point(s): o Progression free survival (PFS), according to EORTC-ISCL-USCLC criteria
o Overall survival (OS)
o Time to response (CR/PR)
o Duration of response
o Time to next systemic treatment
o Evaluate safety and tolerability in this patient population

Secondary ID(s)

1652-CLTF

NCT03357224

Source(s) of Monetary Support

EORTC

F. Hoffmann-La Roche Ltd

Ethics review

Status: Approved
Approval date: 31/01/2019
Contact: