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

Sponsor
Seoul National University Hospital (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05253118
Collaborator
Seoul National University Bundang Hospital (Other)
28
1
1
23
1.2

Study Details

Study Description

Brief Summary

Relapsed or refractory primary DLBCL of the CNS

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This is a multi-center, open label, single arm, phase 2 study designed to evaluate efficacy and safety of tislelizumab (BGB-A317) in combination with pemetrexed in patients with R/R primary DLBCL of the CNS. Twenty-eight patients will be enrolled. Eligible participants will receive combination treatment until disease progression, unacceptable toxicity, or withdrawal of informed consent.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
28 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
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).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).
Masking:
None (Open Label)
Masking Description:
open
Primary Purpose:
Treatment
Official Title:
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)
Anticipated Study Start Date :
Apr 1, 2022
Anticipated Primary Completion Date :
Dec 31, 2023
Anticipated Study Completion Date :
Feb 29, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment

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

    Outcome Measures

    Primary Outcome Measures

    1. Objective response rate [Through study completion, an average of 1 year]

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

    Secondary Outcome Measures

    1. Progression-free survival [Through study completion, an average of 1 year]

      To evaluate progression-free survival (PFS), duration of response (DoR) and overall survival (OS) of tislelizumab plus pemetrexed in R/R primary DLBCL of the CNS

    2. Safety and Tolerability [Through study completion, an average of 1 year]

      To evaluate the safety and tolerability of tislelizumab plus pemetrexed based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) version 5.0

    3. Overall survival [Through study completion, an average of 2 years]

      The length of time from the date of the first treatment to the date of any death or last follow-up

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    19 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments

    2. 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)

    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-containing regimen

    5. 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.

    6. 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.

    7. ECOG performance status 0-2

    8. Adequate organ function as indicated by the following laboratory values, ≤ 28 days prior to randomization or first dose of study drug(s)

    1. 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)

    2. 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

    3. Serum total bilirubin ≤ 1.5 x ULN (total bilirubin must be < 3 x ULN for patients with Gilberts syndrome).

    4. 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

    1. 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

    2. 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)

    Exclusion Criteria:
    1. Secondary CNS lymphoma

    2. Primary ocular lymphoma

    3. A known history of HIV infection

    4. Previous treatment with pemetrexed or immunotherapy including, but not limited to anti-PD-(L)1 antibody and anti-CTLA4 antibody

    5. Radiotherapy to CNS lesions within 4 weeks prior to initiation of study 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 may relapse

    Note: Patients with the following diseases are not excluded and may proceed to further screening:

    1. Controlled Type I diabetes

    2. Hypothyroidism (provided it is managed with hormone replacement therapy only)

    3. Controlled celiac disease

    4. Skin diseases not requiring systemic treatment (e.g., vitiligo, psoriasis, alopecia)

    5. Any other disease that is not expected to recur in the absence of external triggering factors

    6. Any active malignancy ≤ 2 years before the first dose of study drug(s), 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)

    7. 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(s)

    Note: Patients who are currently or have previously been on any of the following steroid regimens are not excluded:

    1. Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent)

    2. Topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with minimal systemic absorption

    3. 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)

    4. With history of interstitial lung disease, non-infectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases, etc.

    5. With severe chronic or active infections requiring systemic antibacterial, antifungal, or antiviral therapy, including tuberculosis infection, etc.

    6. 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

    7. Received therapeutic oral or intravenous antibiotics within 2 weeks before the first drug administration

    8. 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 more than 2 weeks before the treatment.

    9. 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 before the treatment.

    10. Any major surgical procedure requiring general anesthesia ≤ 28 days before the first dose of study drug(s)

    11. Any of the following cardiovascular risk factors:

    12. Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, ≤ 28 days before the first dose of study drug(s)

    13. Pulmonary embolism ≤ 28 days before the first dose of study drug(s)

    14. Any history of acute myocardial infarction ≤ 6 months before the first dose of study

    15. Any history of heart failure meeting New York Heart Association (NYHA) Classification III or IV (Appendix 6) ≤ 6 months before the first dose of study drug(s)

    16. Any event of ventricular arrhythmia ≥ Grade 2 in severity ≤ 6 months before the first dose of study drug(s)

    17. Any history of cerebrovascular accident ≤ 6 months before the first dose of study drug(s)

    18. Uncontrolled hypertension: systolic pressure ≥ 160 mmHg or diastolic pressure ≥ 100 mmHg despite anti-hypertension medications ≤ 28 days before the first dose of study drug(s)

    19. Any episode of syncope or seizure ≤ 28 days before the first dose of study drug(s)

    20. Has received any herbal medicine used to control cancer within 14 days of the first study drug(s) administration.

    21. Patients with toxicities (as a result of prior anticancer therapy) which have not recovered to baseline or stabilized, except for AEs not considered a likely safety risk (e.g., alopecia, neuropathy and specific laboratory abnormalities)

    22. Was administered a live vaccine ≤ 4 weeks before the first dose of study drug(s) Note: Seasonal vaccines for influenza and SARS-CoV-2 (or COVID-19) are generally inactivated vaccines and are allowed. Intranasal vaccines are live vaccines and are not allowed.

    23. Underlying medical conditions (including laboratory abnormalities) or alcohol or drug abuse or dependence that, will be unfavorable for the administration of study drug(s) or affect the explanation of drug toxicity or AEs or result in insufficient or might impair compliance with study conduct.

    24. Concurrent participation in another therapeutic clinical study.

    25. Pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 30 days after the last dose of study drug(s)

    26. History or current evidence of any condition or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Seoul National University Hospital Seoul Korea, Republic of 03080

    Sponsors and Collaborators

    • Seoul National University Hospital
    • Seoul National University Bundang Hospital

    Investigators

    • Principal Investigator: Tae Min Kim, PhD., M.D., Seoul National University Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Tae Min Kim, Principal investigator, Seoul National University Hospital
    ClinicalTrials.gov Identifier:
    NCT05253118
    Other Study ID Numbers:
    • SPECTRUM
    First Posted:
    Feb 23, 2022
    Last Update Posted:
    Feb 23, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Tae Min Kim, Principal investigator, Seoul National University Hospital
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Feb 23, 2022