PARCT: Trial of Atezolizumab in Relapsed/Refractory Cutaneous T Cell Lymphoma (CTCL)

NCT03357224 | Terminated Phase 2 DMC

• 1 other identifier: EORTC 1652-CLTF
• Study Type: interventional
• Target: 26
• Locations: 2 countries
• Sites: 2

Brief Summary

Trial assessing atezolizumab (anti-PD-L1) as treatment option for patients with mycosis fungoides/sezary syndrome having progressed under or after previous therapy For this study, we invite patients suffering from mycosis fungoides and Sézary syndrome who have progressed after initial therapy or have failed to respond to previous therapy. Mycosis fungoides and Sézary syndrome are cancers in which lymphocytes\* become malignant (cancerous) and affect the skin. In mycosis fungoides, the disease is generally limited to the skin, and people develop flat or raised areas on their skin where the lymphocytes have accumulated. Sometimes even larger aggregations of lymphocytes occur in the skin or lymph nodes, resulting in tumors. In Sézary syndrome, the skin is often reddened or itchy, and some abnormal lymphocytes circulate in the blood. \* Lymphocytes are a type of immune cells that is made in the bone marrow and is found in the blood. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infections and other diseases. In standard practice, the disease will be treated with conventional chemotherapy that unfortunately has a limited lasting benefit. In this study, we want to see if a new treatment option can optimize and improve response and make benefit last as long as possible. This new treatment option is immunotherapy, using atezolizumab (Tecentriq). Immunotherapy is a cancer treatment that uses antibodies made in the laboratory from a single type of immune system cell. These antibodies can identify substances on cancer cells or normal cells that may help cancer cell grow. The antibodies attach to the substances and kill the cancer cells, block their growth, or keep them from spreading. Atezolizumab blocks a protein called PD-L1 (programmed death-ligand 1) from binding to its receptor found on the surface of lymphocytes. It helps to restore the immune activity of the body against the cancer. Atezolizumab is already used to treat adults with a cancer that affects the bladder and the urinary system, called urothelial carcinoma, and a cancer that affects the lungs, called non-small cell lung cancer. In this trial, patients will receive atezolizumab for one year unless the tumor starts growing again or this is not considered suitable for them anymore or they wish to stop the treatment.

Conditions

Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides/Sezary Syndrome

Outcome Measures

Primary Outcomes (1)

• Best overall response (CR+PR) rate (EORTC-ISCL-USCLC criteria)

  Overall response rate is defined as the proportion of patients with global response score equal to CR or PR

  Up to maximum 1 year starting from patient registration

Secondary Outcomes (5)

• Progression free survival (EORTC-International Society of Cutaneous Lymphoma (ISCL)-United States Cutaneous Lymphoma Consortium (USCLC) criteria)

  6 months as of Last Patient In (LPI)

• Overall survival (OS)

  5 years as of LPI based on the median overall survival

• Duration of response

  6 months as of LPI

• Time to response (CR/PR)

  6 months as of LPI

• Time to next systemic treatment

  8 months as of LPI

Study Arms (1)

Experimental: Atezolizumab

EXPERIMENTAL

The treatment will be given for a maximum of 1-year unless confirmed disease progression or unless other criteria for treatment discontinuation are met as specified in the protocol.

Drug: Atezolizumab

Interventions

Atezolizumab DRUG

Patients will receive atezolizumab 1200 mg IV Q3w for 1 year.

Also known as: Tecentriq

Experimental: Atezolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients with diagnosis of CTCL (mycosis fungoides or Sézary-Syndrome) tumor stage IIB to IVB
• Mandatory to ship 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-2α 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 109/L (\>3000/mm3);
• Absolute neutrophil count of \>1.5 x 109/L (\>1500/mm3);
• Platelet count \>100 x 109/L (\>100,000/mm3);
• 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 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.

You may not qualify if:

• 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. Campath) within 3 months prior to the first dose of atezolizumab.
• 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 the first dose of study treatment:
• 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

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Hoffmann-La Roche: collaborator

Study Sites (2)

Hospital Universitario 12 De Octubre

Madrid, Spain

Location

UniversitaetsSpital Zurich - Division of Dermatology

Zurich, Switzerland

Location

MeSH Terms

Conditions

Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome

Interventions

atezolizumab

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Rudolf Stadler

  Johannes Wesling Klinikum Minden - Minden, Germany

  STUDY CHAIR

• Robert Knobler

  Medical University Vienna, General Hospital AKH - Vienna, Austria

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2017
• First Posted: November 29, 2017
• Study Start: September 24, 2018
• Primary Completion: March 11, 2021
• Study Completion: August 18, 2022
• Last Updated: February 22, 2024

Record last verified: 2024-02

Locations

CH (1); ES (1)