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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Central Nervous System Lymphoma
• Intervention / Treatment: Drug: ICP-022; Drug: Pemetrexed

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yanyan Liu, M.D. Ph.D; Phone Number: +8613838176375; Email: yyliu@zzu.edu.cn
• Study Contact Backup: Name: Zhihua Yao, M.D. Ph.D; Phone Number: +8613592622292; Email: zlyyyaozhihua1260@zzu.edu.cn

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China
      • Recruiting
      • Henan Cancer Hospital/The affiliated Cancer Hospital of ZhengZhou university
      • Contact: Zhihua Yao, M.D. Ph.D; Phone Number: +8613592622292; Email: zlyyyaozhihua1260@zzu.edu.cn
      • Contact: Zhihua Yao, M.D. Ph.D
      • Contact: Yanyan Liu, M.D. Ph.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age between 18 to 75 years old (including 18 and 75)
2. 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
3. Having at least one measurable lesions
4. 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)
5. Life expectancy no less than 1 month
6. enough main organ function
7. 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
8. Agreeing to sign the written informed consents

Exclusion Criteria:

1. Poor peripheral disease control of secondary central nervous system lymphoma
2. Patients used pemetrexed or orelabrutinib in the past
3. Active malignant tumor need be treated at the same time
4. Other malignant tumor history
5. Serious surgery and trauma less than two weeks
6. Patients with active tuberculosis
7. Systemic therapy for serious acute/chronic infection
8. Congestive heart failure, uncontrolled coronary heart disease, arrhythmia and heart infarction less than 6 months
9. HIV-positive, AIDS patients and untreated active hepatitis
10. Patients with a history of deep vein thrombosis or pulmonary embolism less than 12 months
11. Patients with a history of mental illness or drug abuse
12. Poor compliance during the trial and/or follow-up phase
13. Allergies or people who are known to be allergic to any active ingredients, excipients, mouse-derived products or heterologous protein contained in this trial
14. Researchers determine unsuited to participate in this trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Orelabrutinib Combined with Pemetrexed; 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; Induction Chemotherapy: Orelabrutinib, 150mg/d continuous oral administration (3 weeks/cycle, total 6 cycles). Maintenance Treatment: Orelabrutinib, 150mg/d continuous oral administration (28d/cycle).; Other Names: orelabrutinib; Drug: Pemetrexed; Induction Chemotherapy: Pemetrexed, 500mg/m2, Intravenous administration on day 5 of each 3-week cycle (Total 6 cycles).; Other Names: Pemetrexed injection

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Henan Cancer Hospital
• Investigators: Study Director: Yanyan Liu, M.D. Ph.D, Henan Cancer Hospital; Study Director: Zhihua Yao, M.D. Ph.D, Henan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2021
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): December 21, 2026

Study Registration Dates

• First Submitted: December 26, 2021
• First Submitted That Met QC Criteria: January 22, 2022
• First Posted (Actual): January 26, 2022

Study Record Updates

• Last Update Posted (Actual): April 23, 2025
• Last Update Submitted That Met QC Criteria: April 18, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Relapsed and Refractory; BTK inhibitor; Central Nervous System Lymphoma
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Pemetrexed
• Other Study ID Numbers: HNSZLYYNHL06

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No