Orelabrutinib Combined With Pemetrexed For Relapsed/Refractory Central Nervous System Lymphoma

Study Overview
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Brief Summary
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This is a prospective single arm, phase II clinical trial to observe the efficacy and safety of orelabrutinib combined with pemetrexed in the treatment for patients with relapsed/refractory central nervous system lymphoma.

Official Title
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A Single Arm, Phase II Clinical Trial of Orelabrutinib Combined With Pemetrexed in the Treatment for Patients With Relapsed/Refractory Central Nervous System Lymphoma

Conditions
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Central Nervous System Lymphoma

Intervention / Treatment
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* Drug: ICP-022
* Drug: Pemetrexed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 to 75 years old (including 18 and 75) Diagnosed as diffuse large B-cell lymphoma; Recurrence or progression of central nervous system disease confirmed by imaging ± tissue biopsy pathology or cerebrospinal fluid flow cytometry; Secondary central nervous system lymphoma can also be admitted when the systemic disease is well controlled Having at least one measurable lesions World health organization-Eastern Cooperative Oncology Group Performance Status (ECOG) 0-2 ( ECOG 3 due to tumors can be included after being fully assessed by the investigator) Life expectancy no less than 1 month enough main organ function Pregnancy test within 7 days must be negative for women of childbearing period, and appropriate measures should be taken for contraception for women in childbearing period during the study and six months after this study Agreeing to sign the written informed consents Exclusion Criteria: Poor peripheral disease control of secondary central nervous system lymphoma Patients used pemetrexed or orelabrutinib in the past Active malignant tumor need be treated at the same time Other malignant tumor history Serious surgery and trauma less than two weeks Patients with active tuberculosis Systemic therapy for serious acute/chronic infection Congestive heart failure, uncontrolled coronary heart disease, arrhythmia and heart infarction less than 6 months HIV-positive, AIDS patients and untreated active hepatitis Patients with a history of deep vein thrombosis or pulmonary embolism less than 12 months Patients with a history of mental illness or drug abuse Poor compliance during the trial and/or follow-up phase Allergies or people who are known to be allergic to any active ingredients, excipients, mouse-derived products or heterologous protein contained in this trial Researchers determine unsuited to participate in this trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Orelabrutinib Combined with Pemetrexed<br>Induction Chemotherapy: Orelabrutinib, 150mg/d continuous oral administration, Pemetrexed, 500mg/m2, Intravenous administration on day 5 of each 3-week cycle (Total 6 cycles). Maintenance Treatment: Orelabrutinib, 150mg/d continuous oral administration (28d/cycle). | Drug: ICP-022<br>* Induction Chemotherapy: Orelabrutinib, 150mg/d continuous oral administration (3 weeks/cycle, total 6 cycles). Maintenance Treatment: Orelabrutinib, 150mg/d continuous oral administration (28d/cycle).<br>* Other names: orelabrutinib;Drug: Pemetrexed<br>* Induction Chemotherapy: Pemetrexed, 500mg/m2, Intravenous administration on day 5 of each 3-week cycle (Total 6 cycles).<br>* Other names: Pemetrexed injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate | the total proportion of patients with complete response (CR) and partial response (PR) | every 6 weeks from the day of the first cycle of induction chemotherapy treatment (each cycle is 21 days) and every 8 weeks from the day of the first cycle of maintenance treatment to 5 years after last patient's enrollment (each cycle is 28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival | the total proportion of patients with no progression from date of the first day of treatment to the date of confirmed progressive disease or death which one occurs first | every 6 weeks from the day of the first cycle of induction chemotherapy treatment (each cycle is 21 days) and every 8 weeks from the day of the first cycle of maintenance treatment to 5 years after last patient's enrollment (each cycle is 28 days) | 
| overall survival | from date of first day of treatment to the date of death by any cause | every 6 weeks from the day of the first cycle of induction chemotherapy treatment (each cycle is 21 days) and every 8 weeks from the day of the first cycle of maintenance treatment to 5 years after last patient's enrollment (each cycle is 28 days) | 
| The incidence of grade 3-4 adverse events | the incidence of grade 3 or 4 adverse events (based on NCI CTC-AE v5.0) | up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Central Nervous System Lymphoma, BTK inhibitor, Relapsed and Refractory