ZR-MTX for PIOL Phase II Trial

NCT06973811 | Not Yet Recruiting Phase 2

• 1 other identifier: K6396
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective single-arm phase II study, with the purpose of evaluating the efficiency of ZR-MTX regimen (Rituximab, Zanubrutinib and methotrexate) combined with intravitreal methotrexate, then followed by minimal residual disease directed Zanubrutinib maintenance in newly-diagnosed primary intraocular lymphoma. The primary endpoint of this study is progression-free survival (PFS).

Conditions

Primary Intraocular Lymphoma

Keywords

primary intraocular lymphoma

Outcome Measures

Primary Outcomes (1)

• 2 years progression-free survival

  2 years progression-free survival was calculated from the date of therapy until death from lymphoma or 2-year follow up without relapsing

  from the date of treatment to the subject finished his 2 years follow-up phase or the disease relapsed or the death due to lymphoma

Secondary Outcomes (1)

• overall response rate (ORR)

  4 weeks after the end of 6 cycles of induction (each cycle is 21 days).

Study Arms (1)

ZRMTX

EXPERIMENTAL

Zanubrutinib/Rituximab/IV MTX \& intravitreal MTX Experimental arm will be treated with rituximab plus zanubrutinib (ZR) regimen for 4 cycles, ZR plus iv MTX for 2 cytles and followed by zanubrutinib maintenance for 2 years ( or choose to stop zanubrutinib maintenance if reached CR with negative CSF cfDNA). Meanwhile, intravitreal methotrexate will be given as protocol during the 1st year of treatment.

Drug: Methotrexate; Drug: Rituximab (R); Drug: Zanubrutinib; Drug: Methotrexate (MTX)

Interventions

Methotrexate DRUG

400ug intravitreal injection every week for 4 doses in the induction phase, every 2 weeks for 2 doses as consolidation, then every month for 10 doses

ZRMTX

Rituximab (R) DRUG

Rituximab 375mg/m2 intravenous infusion d1, every 21 days for 1 cycle. 6 cycles will be prescribed as protocol

ZRMTX

Zanubrutinib DRUG

160mg Bid, oral. 21-day cycle for 6 cycles in the induction phase and for 2 years in the maintenance phase

ZRMTX

Methotrexate (MTX) DRUG

Methotrexate 3.5g/m2 intravenous infusion d1, every 21 days for cycle 5 and 6 only.

ZRMTX

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly-diagnosed primary vitreoretinal lymphoma
• ECOG≤2
• creatinine clearance rate (CCR) ≥ 60ml/h, according to Cockcroft-Gault
• Total bilirubin # 2 upper limits of normal, alanine aminotransferase#ALT# \< 3 upper limits of normal
• Sign the Informed consent
• Women of childbearing potential must understand that the study medication could have a potential teratogenic risk. They should undergo complete contraception during the study period.
• Male subjects must agree to use condoms throughout study drug therapy.

You may not qualify if:

• primary central nervous system lymphoma involved eyes and brain
• systemic B cell lymphoma involved eyes
• Pre-existing uncontrolled active infection
• Clinical evidence of grade 3 or 4 heart failure as defined by the New York Heart Association criteria
• Pregnancy or active lactation
• Co-existing tumors
• HIV or HBV or HCV infection

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Location

MeSH Terms

Conditions

Intraocular Lymphoma

Interventions

Methotrexate; Rituximab; zanubrutinib

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Eye Neoplasms; Neoplasms by Site; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

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

Central Study Contacts

Wei Zhang, M.M.

CONTACT

13681473557; vv1223@vip.sina.com

Study Design

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

Study Record Dates

• First Submitted: May 6, 2025
• First Posted: May 15, 2025
• Study Start: May 10, 2025
• Primary Completion (Estimated): October 30, 2027
• Study Completion (Estimated): October 30, 2029
• Last Updated: May 20, 2025

Record last verified: 2025-05

Locations

CN (1)