Trial Title:
A Study of GNC-038, a Tetra-specific Antibody, in Patients With Central Nervous System Lymphoma (PCNSL) and Relapsed or Refractory Secondary Central Nervous System Lymphoma (SCNSL)
NCT ID:
NCT05485753
Condition:
Primary Central Nervous System Lymphoma
Secondary Central Nervous System Lymphoma
Conditions: Official terms:
Lymphoma
Neoplasm Metastasis
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
GNC-038
Description:
Administration by intravenous infusion
Arm group label:
Study treatment
Summary:
In this study, the safety and preliminary efficacy of GNC-038 in patients with r relapsed
or refractory primary central nervous system lymphoma (PCNSL) and relapsed or refractory
secondary central nervous system lymphoma (SCNSL) will be investigated to assess the
dose-limiting toxicity (DLT), maximum tolerated dose (MTD) or maximum administered dose
(MAD) for MTD is not reached of GNC-038. The recommended dose for phase II (RP2D)
clinical study will also be determined.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
-
1. The subject can understand the informed consent, participate in and sign the
informed consent voluntarily;
-
2. No gender limitation;
-
3. Age: ≥18;
-
4. Expected survival time ≥3 months;
-
5. Patients with primary CNS lymphoma (PCNSL) and secondary CNS lymphoma (SCNSL)
confirmed by histology or cytology;
-
6. A. Patients with recurrent/refractory primary central nervous system lymphoma
(PCNSL) and recurrent/refractory secondary central nervous system lymphoma
(SCNSL) may be associated with ocular lymphoma;B. Patients with relapsed or
refractory primary CNS lymphoma (PCNSL) and relapsed or refractory secondary
CNS lymphoma (SCNSL) who were not eligible or intolerant to other therapies
were determined by the investigator;Recurrence and refractory are defined as
follows: Recurrence refers to the emergence of new lesions after adequate
treatment to complete response (CR).Refractory refers to a patient who has
experienced at least first-line treatment without disease remission, e.g.
induction chemotherapy with methotrexate without CR.
-
7. KPS score ≥60;
-
8. Adverse reactions of previous antitumor therapy returned to CTCAE 5.0 grade ≤1
(except for the indicators that the researchers considered to be related to the
disease, such as anemia, and toxicities that the researchers determined to be
without safety risk, such as alopecia, grade 2 peripheral neurotoxicity,
hypothyroidism stabilized by hormone replacement therapy, etc.);
-
9. Before the first administration, the organ function level should meet the
following requirements:
Bone marrow function: In the absence of blood transfusion, G-CSF (long-acting white
needle within 2 weeks) and medication correction within 7 days prior to screening:
Absolute neutrophil count (ANC) ≥15×10^9/L (subjects with bone marrow infiltration should
be ≥0.5×10^9/L);Hemoglobin ≥90 g/L;Platelet count ≥90×10^9/L; Liver function: Total
bilirubin ≤1.5 ULN (Gilbert's syndrome ≤3 ULN), transaminase (AST/ALT) ≤2.5 ULN (≤5.0 ULN
for subjects with tumor invasive changes in the liver) without correction with
hepatoprotective drugs within 7 days prior to screening; Renal function: Creatinine (Cr)
≤1.5 ULN and creatinine clearance (Ccr) ≥50 mL /min according to the Cockcroft and Gault
formula; Routine urine / 24-hour urine protein quantification: qualitative urine protein
≤1+ (if qualitative urine protein ≥2+, 24-hour urine protein < 1g can be included);
Cardiac function: left ventricular ejection fraction ≥50%; Coagulation function:
fibrinogen ≥1.5g/L; Activated partial thrombin time (APTT) ≤1.5 ULN; Prothrombin time
(PT) ≤1.5 ULN.
-
10. Fertile female subjects or male subjects with fertile partners must use highly
effective contraception beginning 7 days before the first dose and up to 12
weeks after the last dose. Fertile female subjects must have a negative
serum/urine pregnancy test within 7 days prior to initial dosing;
-
11. The subject is able and willing to follow the visits, treatment plans,
laboratory tests, and other study-related procedures specified in the study
protocol.
Exclusion Criteria:
-
1. Lung disease defined as grade ≥3 according to NCI-CTCAE V5.0; Patients with
current interstitial lung disease (ILD) (except those who have recovered from
previous interstitial pneumonia);
-
2. Active infections requiring systemic treatment, such as severe pneumonia,
bacteremia, sepsis, etc.;
-
3. Active tuberculosis;
-
4. Brain stem tumor infiltration or only eye lesions;
-
5. Patients with active autoimmune diseases, such as: Systemic lupus
erythematosus, systemic treatment of psoriasis, rheumatoid arthritis,
inflammatory bowel disease, and hashimoto's thyroiditis, etc., with the
exception of type I diabetes, only replacement therapy can control the
hypothyroidism, no systemic treatment of skin disease (e.g., vitiligo,
psoriasis), B cells caused by autoimmune disease;
-
6. Non-melanoma skin cancer in situ, superficial bladder cancer, cervical cancer
in situ, gastrointestinal intramucosal cancer, breast cancer, localized
prostate cancer and other cancers that have been cured and have not recurred
within 5 years prior to the first administration are excluded;
-
7. HBsAg positive or HBcAb positive, and HBV-DNA test ≥ the upper limit of normal;
HCV antibody positive and HCV-RNA≥ the upper limit of normal value; HIV
antibody positive;
-
8. Poorly controlled hypertension (systolic blood pressure >150 mmHg or diastolic
blood pressure >100 mmHg);
-
9. Have a history of serious cardiovascular and cerebrovascular diseases,
including but not limited to: Severe cardiac rhythm or conduction
abnormalities, such as ventricular arrhythmias and degree ⅲ ATrioventricular
block requiring clinical intervention; Longer QT interval at rest (QTc > 450
msec for men or 470 msec for women); Acute coronary syndrome, congestive heart
failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular
and cerebrovascular events occurred within 6 months prior to first
administration; Heart failure with the New York Heart Association (NYHA) Heart
function rating ≥II; 10. Patients with a history of allergy to recombinant
humanized antibodies or to any excipient ingredient of GNC-038;
-
11. Pregnant or breastfeeding women;
-
12. Patients who cannot tolerate MRI examination;
-
13. Patients who underwent major surgery within 28 days prior to administration of
the drug in this study, or who planned to undergo major surgery during the
study period (except for puncture or biopsy surgery);
-
14. Prior organ transplantation or allogeneic hematopoietic stem cell
transplantation (ALLO-HSCT);
-
15. Autologous hematopoietic stem cell transplantation (AUTO-HSCT) within 12 weeks
prior to initiation of GNC-038 therapy;
-
16. Immunosuppressants are being used, including but not limited to: Cyclosporine,
tacrolimus, etc. within 2 weeks prior to gnC-038 treatment; Gnc-038 received a
high dose of glucocorticoid for 2 weeks prior to treatment (longer than 14
days, a steady dose of dexamethasone >5mg per day or equivalent dose of other
glucocorticoids);
-
17. Received radiotherapy within 4 weeks prior to initiation of GNC-038 treatment;
-
18. Received anti-CD20 or anti-CD79B treatment within 4 weeks prior to initiation
of GNC-038 and still responded;
-
19. Received chemotherapy and small molecule targeted therapy within 2 weeks prior
to treatment;
-
20. Received CAR-T therapy within 12 weeks prior to initiation of GNC-038;
-
21. Participated in any other clinical trials within 4 weeks prior to
administration of this trial;
-
22. Past or present central nervous system disease, including, but not limited to,
stroke (imaging)
-
23. Medical examination indicated "lacunar cerebral infarction" except those
requiring no treatment), severe brain injury, Senile dementia, Parkinson's
disease, organic brain syndrome, psychosis;
-
24. Other conditions that the investigator considers inappropriate for
participation in this clinical trial.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
Accepts Healthy Volunteers
Locations:
Facility:
Name:
Beijing Tiantan Hospital, Capital Medical University
Address:
City:
Beijing
Zip:
100070
Country:
China
Status:
Recruiting
Contact:
Last name:
Wenbin Li, PHD
Phone:
010-59975332
Email:
neure55@126.com
Investigator:
Last name:
Wenbin Li
Email:
Principal Investigator
Facility:
Name:
Beijing GoBroad Boren Hospital
Address:
City:
Beijing
Country:
China
Status:
Recruiting
Contact:
Last name:
Kai Hu Hu
Facility:
Name:
Guangdong Provincial People's Hospital
Address:
City:
Guangzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Wenyu Li
Facility:
Name:
The First Affiliated Hospital of Zhengzhou University
Address:
City:
Zhengzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Mingzhi Zhang
Start date:
February 10, 2023
Completion date:
May 2025
Lead sponsor:
Agency:
Sichuan Baili Pharmaceutical Co., Ltd.
Agency class:
Industry
Collaborator:
Agency:
SystImmune Inc.
Agency class:
Industry
Collaborator:
Agency:
Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
Agency class:
Industry
Source:
Sichuan Baili Pharmaceutical Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05485753
