Rituximab,Zanubrutinib in Combination With Lenalidomide, Followed by Zanubrutinib or Lenalidomide Maintenance in Patients With Primary or Secondary CNS Lymphoma

Central Nervous System Lymphoma Clinical Trial

Official title:

Rituximab,Zanubrutinib in Combination With Lenalidomide, Followed by Zanubrutinib or Lenalidomide Maintenance in Patients With Primary or Secondary CNS Lymphoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04938297
• Other study ID #: ZR2 for PCNSL/SCNSL
• Status: Recruiting
• Phase: Phase 2
• Start date: May 26, 2021
• Est. completion date: December 31, 2025

Study information

• Verified date: June 2021
• Source: Henan Cancer Hospital
• Contact: Keshu Zhou, Dr.
• Phone: 13674902391
• Email: drzhouks77[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In view of the synergistic effects of rituximab, zanubrutinib, and lenalidomide and severe complications caused by current standard chemotherapy regimens in Patients for primary or secondary CNS lymphoma, we intend to conduct a prospective clinical study to evaluate the efficacy and toxicity of Rituximab, Zanubrutinib in combination with Lenalidomide. Besides, the efficacy of Zanubrutinib or Lenalidomide in maintenance was also compared.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 31, 2025
• Est. primary completion date: October 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• voluntarily participate in clinical research, fully understand the study and sign the informed consent form (ICF), willing to follow and be able to complete all research steps
• histologically confirmed diffuse large B-cell lymphoma (DLBCL), all subjects must provide enough archived or fresh tumor tissue samples for immunhistochemistry (IHC) and gene expression profile (GEP) evaluation
• For untreated primary CNS lymphoma, patients should be with an age of 65 years or older, intolerable to first-line treatment
• Recurrent or refractory disease was defined as: 1) recurrence of disease after complete remission (CR), or 2) partial remission (PR), stable disease (SD), or progressive disease (PD) at the time of completion of treatment before inclusion
• Recurrent / refractory diffuse large B-cell lymphoma with CNS involvement confirmed by histopathology or imaging
• Age = 18 years, ECoG score = 2, expected survival time is more than 3 months
• Patients with solid lesions must obtain clear evidence of disease progression through imaging examination (head MRI or head CT) 21 days before enrollment. For patients with leptomeningeal involvement only, CSF cytology examination must confirm lymphoma cells and / or imaging findings consistent with CSF disease 21 days before enrollment (at the discretion of the investigator)
• With sufficient organ and bone marrow function , and no severe hematopoietic, heart, lung, liver, kidney, thyroid dysfunction and immune deficiency
• at least 100 days after transplantation for recurrent patients after ATST

Exclusion Criteria:

• Histologically transformed large cell lymphoma
• History of previous transplantation of allogeneic stem cells
• Received BTKi or Lenalidomide
• Received corticosteroid within 7 days for antitumor treatment
• Received chemotherapy, radiotherapy, monoclonal antibody, experimental treatment, or traditional Chinese Medicine within 4 weeks
• Received major surgery within 4 weeks
• Active malignant diseases within 2 years before entering the study
• Clinically significant cardiovascular diseases
• History of severe bleeding diseases
• history of stroke or intracranial hemorrhage within 6 months before the first administration
• Unable to swallow capsules or have diseases that significantly affect gastrointestinal function
• Uncontrolled systemic infection requiring parenteral anti infective therapy
• HIV infection or indicate active hepatitis B or C virus infection
• Drug allergies or metabolic disorders
• Pregnant or lactating women
• Any life-threatening diseases, medical conditions or organ system dysfunction that the researchers believe may affect the safety of the subjects or lead to research risks
• Required to continuously treated with potent and moderate CYP3A inhibitors or inducers
• History of deep venous thrombosis (DVT) or pulmonary embolism (PE) in the past 12 months

Related Conditions & MeSH terms

• Central Nervous System Lymphoma
• Lymphoma

Intervention

Drug:
• Rituximab, Lenalidomide, Zanubrutinib
Induction therapy: Rituximab 375 mg / m2, day 1, Zanubrutinib 160 mg bid, orally, Lenalidomide 25mg QD, orally on day 1-21, 28 days as a course of treatment, 8 courses of treatment.
• Lenalidomide, Zanubrutinib
Maintenance therapy: Lenalidomide: 25mg qd (adjusted according to hectogram condition) or Zanubrutinib 160 mg bid. Continuously use for 2 years or until disease progression
• Lenalidomide
Maintenance therapy: Lenalidomide: 25mg qd (adjusted according to hectogram condition) . Continuously use for 2 years or until disease progression

Locations

Country	Name	City	State
China	Henan cancer hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Henan Cancer Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate	To evaluate the overall response rate of ZR2 in the treatment of CNS Lymphoma	at the end of 8 cycles of induction therapy (each cycle is 28 days)
Secondary	Overall response rate		at the end of 4 cycles of induction therapy (each cycle is 28 days) and 1 year of maintenance therapy
Secondary	Progression-free survival (PFS) rate		at the end of 8 cycles of induction therapy (each cycle is 28 days), 1 year and 2 year of maintenance therapy
Secondary	Overall survival(OS)rate		at the end of 8 cycles of induction therapy (each cycle is 28 days), 1 year and 2 year of maintenance therapy
Secondary	Treatment related adverse events		at the end of 8 cycles of induction therapy (each cycle is 28 days), 1 year and 2 year of maintenance therapy