First-line Treatment of PCNSL With the Combination of Orelabrutinib, Rituximab, and Methotrexate (ORM Regimen)

NCT06454266 | Completed Phase 2

• 1 other identifier: Ningbo103
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

Exploring the efficacy and safety of first-line treatment of primary central nervous system lymphoma with the combination of orelabrutinib, rituximab and methotrexate (ORM regimen).

Conditions

Primary Central Nervous System Lymphoma

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  Proportion of CR and PR subjects will be assessed at 8 courses

  up to 8 months

Secondary Outcomes (4)

• Progress free survival time

  up to36 months

• Overall survival

  up to36 months

• Adverse events profile

  up to 8 months

• MRD defined by cerebrospinal fluid ctDNA

  up to 8 months

Study Arms (1)

ORM regimen(Orelabrutinib, Rituximab and Methotrexate)

EXPERIMENTAL

The subjects received ORM regimen treatment every 21 days for a total of 6 cycles.

Drug: ORM regimen

Interventions

ORM regimen DRUG

The subjects received ORM regimen treatment every 21 days for a total of 6 cycles. The specific medication is as follows " Obutinib tablets 150mg qd d1-21 (suspended 2 days before MTX use until MTX drops to safe concentration) Rituximab 375mg/m2, d1 Methotrexate 3g/m2, d2

Also known as: Orelabrutinib, Rituximab and Methotrexate

ORM regimen(Orelabrutinib, Rituximab and Methotrexate)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of primary central nervous system lymphoma (PCNSL) of B cell origin，confirmed by pathology (histology or cytology).
• The patient voluntarily signs the informed consent form.
• ECOG≤3 points.
• According to the judgment of the researcher, the expected survival period is more than 3 months.
• Have measurable lesions, and brain contrast-enhanced MRI shows solid lesions (\>10\*10mm) ; for those with only meningeal lesions, cytological examination of cerebrospinal fluid (CSF) is required to confirm lymphoma cells and/or imaging findings and CSF examination was consistent.
• No previous systemic treatment for lymphoma, except corticosteroids;
• Bone marrow and organ function meet the following standards (no blood transfusion, no use of G-CSF, no use of drug correction within 14 days before screening):
• ① Bone marrow function: Absolute value of neutrophils ≥1.5×109/L, platelets
• ×109/L, hemoglobin ≥80g/L;
• Liver function: serum total bilirubin ≤1.5×ULN (≤3.0×ULN, if there is liver metastasis ); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN (≤ 5.0 × ULN, if there is liver metastasis); ③ Coagulation function: International normalized ratio (INR) and activated partial thrombin time ≤ 1.5 × ULN ;
• Renal function: Serum creatinine ≤ 1.5 × ULN or estimated creatinine clearance ≥ 60 mL/min (male: Cr (ml/min) = (140-age) × weight (kg) / 72 × serum creatinine concentration (mg/dl) ); Female: Cr (ml/min) = (140-age) × weight (kg)/85 × serum creatinine concentration (mg/dl)).
• Female subjects of childbearing age and male subjects with childbearing potential who have no childbearing plans with their partners during the study and within 3 months after discontinuing treatment must take one of the following measures during the entire study and within 3 months of discontinuing treatment. Effective contraception: abstinence, physical contraception (such as ligation, condoms, etc.), and the use of hormonal contraceptives should be started at least 3 months before the first dose of medication. Male subjects are prohibited from donating sperm within 3 months from the start of treatment to the end of treatment. The patient or legal guardian voluntarily signed the informed consent form.
• Good compliance and willingness to comply with visit schedule, dosing plan, laboratory examinations and other test steps.

You may not qualify if:

• The pathological diagnosis was T-cell lymphoma;
• Have other tumors that require treatment;
• Uncontrollable active infection;
• Have uncontrollable or important cardiovascular diseases, including (but not limited to):
• Any of the following occurring within 6 months before the first dose Conditions: congestive heart failure (NYHA class III or IV), myocardial infarction, unstable angina, or arrhythmia requiring treatment at screening, left ventricular ejection fraction (LVEF) \<50%;
• Primary cardiomyopathy (such as dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, indeterminate cardiomyopathy); ③ History of clinically significant QTc phase prolongation, II degree type II atrioventricular conduction resistance lag or III degree atrioventricular block or QTc interval (F method) \>470msec (female) or \>480msec (male); ④ Atrial fibrillation (EHRA grade ≥ 2b); ⑤ Uncontrollable hypertension, as determined by the researcher were judged not to be suitable to participate in this study.
• Suffering from active hepatitis B or C infection (hepatitis B: acute hepatitis B, untreated chronic hepatitis B virus infection, chronic hepatitis B carriers with HBV-DNA ≥ the detection limit of each center; hepatitis C: HCVRNA positive) or syphilis . Note: Inactive HBV surface antigen (HBsAg) carriers, subjects with active HBV infection and long-lasting anti-HBV suppression (HBV DNA \<detection limit of each center), and subjects who have been cured of HCV can be enrolled.
• HIV-infected patients;
• Have ever received an organ transplant or allogeneic stem cell transplant.
• For female subjects, currently in pregnancy or lactation.
• Those who have previously or currently have pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, etc., and are judged by the researcher to be unsuitable to participate.
• There have been autoimmune diseases requiring systemic treatment (i.e., disease-modifying antirheumatic drugs, hormones or immunosuppressants) in the past 2 years, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, etc. Rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome-associated vascular thrombosis, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis or glomerulonephritis. The following situations are allowed: autoimmune hypothyroidism or type I diabetes under stable treatment, hormone replacement therapy (such as thyroxine, insulin, or physiological hormone supplementation due to adrenal or pituitary insufficiency) is not considered systemic therapy and is allowed Join the group.

Sponsors & Collaborators

• Ningbo No. 1 Hospital: lead

Study Sites (1)

The First Affiliated Hospital of Ningbo University

Ningbo, Zhejiang, 315010, China

Location

MeSH Terms

Interventions

orelabrutinib; Rituximab; Methotrexate

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Shaoying Chen

  First Affiliated Hospital of Ningbo University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 5, 2024
• First Posted: June 12, 2024
• Study Start: December 28, 2021
• Primary Completion: June 30, 2024
• Study Completion: July 25, 2024
• Last Updated: July 30, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)