Phase II study of tislelizumab plus pemetrexed in patients with relapsed or refractory primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (CNS)

Not Applicable

Active, not recruiting

• Conditions: Neoplasms

• Registration Number: KCT0007048
• Lead Sponsor: Seoul National University Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Active, not recruiting
• Sex: All
• Target Recruitment: 28

Inclusion Criteria

1.Signed and dated written informed consent.
2.Age of 19 years or older on the day of signing the informed consent form
3.Histologically confirmed primary DLBCL of the CNS in the local lab
4.Relapsed or refractory disease with failure to at least one line of chemotherapy including high-dose methotrexate-based regimen
5.At least one bi-dimensionally measurable lesion per IPCG response criteria
6.Mandatory provision of NGS data or formalin-fixed paraffin-embedded (FFPE) archival tissues
7.European Cooperative Oncology Group (ECOG) performance status from 0 to 2
8.Adequate organ function at screening as follows:
a.Absolute neutrophil count (ANC) = 1.5 x 109/L; Platelets = 75 x109/L; Hemoglobin = 9.0 g/dL
b.Serum creatinine = 1.5 x upper limit of normal (ULN) or estimated glomerular filtration rate = 45 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration equation
c.Serum total bilirubin = 1.5 x ULN, or = 3 x UNL for patients with known Gilbert’s syndrome
d.Aspartate transaminase (AST) and alanine transaminase (ALT) = 3 x ULN if no demonstrable liver metastases, or = 5 x ULN if transaminase elevation is attributable to liver metastases
9.Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and for = 120 days after the last dose of study drug(s) and must have a negative urine (or serum) pregnancy test = 7 days before initial treatment
10.Nonsterile males must be willing to use a highly effective method of birth control for the duration of the study and for = 120 days after the last dose of study drug (a ‘sterile’ male is defined as one for whom azoospermia has been previously demonstrated in a semen sample examination as definitive evidence of infertility)

Exclusion Criteria

1.Secondary CNS lymphoma
2.Primary ocular lymphoma
3.A known history of HIV infection
4.Previous receipt of pemetrexed or immunotherapy including, but not limited to anti-PD(L)-1 and anti-CTLA4 antibody
5.Radiotherapy to CNS lesions within 4 weeks prior to start of the treatment
6.Autologous stem cell transplantation as a part of treatment for primary DLBCL of the within 90 days prior to the start of the treatment
7.Has received any chemotherapy, targeted therapy, or any investigational therapies including investigational vaccine within 14 days or 5 half-lives (whichever is shorter) of the first study drug(s) administration
8.Known hypersensitivity or intolerance to pemetrexed or tislelizumab (BGB-A317)
9.Active autoimmune diseases or history of autoimmune diseases that have high risk of relapse.
Note: Patients with the following diseases are not excluded:
a.Controlled Type I diabetes
b.Hypothyroidism (provided it is managed with hormone replacement therapy only)
c.Controlled celiac disease
d.Skin diseases not requiring systemic treatment (e.g., vitiligo, psoriasis, alopecia)
e.Any other disease that is not expected to recur in the absence of external triggering factors
10.Any active malignancy = 2 years before the first dose of study drug, except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (e.g., resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast)
11.Any condition that required systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication = 14 days before the first dose of study drug
Note: Patients who are currently or have previously been on any of the following steroid regimens are not excluded:
a.Adrenal replacement steroid (= 10 mg daily of prednisone or equivalent)
b.Topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with minimal systemic absorption
c.Short course (= 7 days) of corticosteroid prescribed prophylactically (e.g., for contrast dye allergy) or for the treatment of a non-autoimmune condition (e.g., delayed-type hypersensitivity reaction caused by contact allergen)
12.With history of interstitial lung disease, non-infectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases, etc.
13.With severe chronic or active infections requiring systemic antibacterial, antifungal, or antiviral therapy, including tuberculosis infection, etc.
a.Severe infections within 4 weeks before the first dose of study drug(s), including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
b.Received therapeutic oral or intravenous antibiotics within 2 weeks before the first drug administration
14.Patients with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers whose HBV DNA is = 20 IU/mL
Note: Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B (HBV DNA < 20 IU/mL) can be enrolled. Patient taking antiviral agents should have received it for more than 2 weeks before the treatment.
15.Patients with active hepatitis C virus (HCV)
Note: Hepatitis C antibody (anti-HCV) is negative or anti-HCV positive with undetectable HCV RNA (< 15 IU/mL) can be enrolled. Patient taking antiviral agents should have received it more than 2 weeks b

Study & Design

• Study Type: Interventional Study
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Objective response rate

Secondary Outcome Measures

Name	Time	Method
Progression free survival;Duration of response;Overall survival;Safety and Tolerability