Relapsed or Refractory Primary Diffuse Large B-cell Lymphoma (DLBCL) of the Central Nervous System (CNS)

NCT05253118 | Active Not Recruiting Phase 2

• 1 other identifier: SPECTRUM
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

Relapsed or refractory primary DLBCL of the CNS

Conditions

DLBCL

Keywords

DLBCL; Tislelizumab; Pemetrexed; relapsed or refractory primary diffuse large B-cell lymphoma; R/R primary DLBCL

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  To evaluate objective response rate (ORR) of tislelizumab (BGB-A317) plus pemetrexed in R/R primary DLBCL of the CNS

  Through study completion, an average of 1 year

Secondary Outcomes (3)

• Progression-free survival

  Through study completion, an average of 1 year

• Safety and Tolerability

  Through study completion, an average of 1 year

• Overall survival

  Through study completion, an average of 2 years

Study Arms (1)

Treatment

EXPERIMENTAL

Tislelizumab (BGB-A317) 200mg will be administered on Day 1 of each 21-day cycle (once every 3 weeks) in combination with pemetrexed. And pemetrexed 500 mg/m2 will be administered on Day 1 of each 21-day cycle (once every 3 weeks).

Drug: Tislelizumab; Drug: Pemetrexed

Interventions

Tislelizumab DRUG

Tislelizumab (BGB-A317) 200mg will be administered on Day 1 of each 21-day cycle (once every 3 weeks) in combination with pemetrexed.

Also known as: BGB-A317

Treatment

Pemetrexed DRUG

Pemetrexed 500 mg/m2 will be administered on Day 1 of each 21-day cycle (once every 3 weeks).

Treatment

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments
• Age of 19 years or older on the day of signing the informed consent form (or the legal age of consent in the jurisdiction in which the study is taking place)
• Histologically confirmed primary DLBCL of the CNS in the local lab
• Relapsed or refractory disease with failure to at least one line of chemotherapy including high-dose methotrexate-containing regimen
• At least one bi-dimensionally measurable lesion per IPCG response criteria Note: A lesion in an area subjected to prior locoregional therapy, including previous radiotherapy, is not considered measurable unless there has been demonstrated progression after the therapy as defined by IPCG response criteria.
• Mandatory provision of next-generation sequencing (NGS) data or formalin-fixed paraffin-embedded (FFPE) archival tissue Note: Patients should submit 2 unstained slides and at least 5 cuts of tissue in 10-μm thickness. If there is local NGS data, at least 2 unstained slides are acceptable.
• ECOG performance status 0-2
• Adequate organ function as indicated by the following laboratory values, ≤ 28 days prior to randomization or first dose of study drug(s)
• a. Patients must not have required a blood transfusion or growth factor support ≤ 14 days before sample collection at screening for the following: i. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L ii. Platelets ≥ 75 x 109/L iii. Hemoglobin ≥ 90 g/L (9.0 g/dL)
• b. Serum creatinine ≤ 1.5 x ULN (upper limit of normal) or estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration equation
• c. Serum total bilirubin ≤ 1.5 x ULN (total bilirubin must be \< 3 x ULN for patients with Gilberts 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
• Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and ≥ 120 days after the last dose of study drug(s), and have a negative urine (or serum) pregnancy test ≤ 7 days before initial treatment
• Non-sterile males must be willing to use a highly effective method of birth control and not donate/bank sperm for the duration of the study and for ≥ 120 days after the last dose of tislelizumab (a 'sterile' male is defined as one for whom azoospermia has been previously demonstrate in a semen sample examination as definitive evidence of infertility)

You may not qualify if:

• Secondary CNS lymphoma
• Primary ocular lymphoma
• A known history of HIV infection
• Previous treatment with pemetrexed or immunotherapy including, but not limited to anti-PD-(L)1 antibody and anti-CTLA4 antibody
• Radiotherapy to CNS lesions within 4 weeks prior to initiation of study treatment
• Autologous stem cell transplantation as a part of treatment for primary DLBCL of the within 90 days prior to the start of the treatment
• 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
• Known hypersensitivity or intolerance to pemetrexed or tislelizumab (BGB-A317)
• Active autoimmune diseases or history of autoimmune diseases that may relapse
• Note: Patients with the following diseases are not excluded and may proceed to further screening:
• Controlled Type I diabetes
• Hypothyroidism (provided it is managed with hormone replacement therapy only)
• Controlled celiac disease
• Skin diseases not requiring systemic treatment (e.g., vitiligo, psoriasis, alopecia)
• Any other disease that is not expected to recur in the absence of external triggering factors

Sponsors & Collaborators

• Seoul National University Hospital: lead
• Gyeongsang National University Hospital: collaborator
• Kyunghee University Medical Center: collaborator
• Inje University Haeundae Paik Hospital: collaborator
• Chungnam National University Hospital: collaborator

Study Sites (1)

Seoul National University Hospital

Seoul, 03080, South Korea

Location

MeSH Terms

Conditions

Recurrence

Interventions

tislelizumab; Pemetrexed

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Tae Min Kim, PhD., M.D.

  Seoul National University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: open
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: Tislelizumab (BGB-A317) 200mg will be administered on Day 1 of each 21-day cycle (once every 3 weeks) in combination with pemetrexed. And pemetrexed 500 mg/m2 will be administered on Day 1 of each 21-day cycle (once every 3 weeks).

Study Record Dates

• First Submitted: February 6, 2022
• First Posted: February 23, 2022
• Study Start: August 18, 2022
• Primary Completion (Estimated): December 28, 2026
• Study Completion (Estimated): December 28, 2026
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)