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

Sponsor

Henan Cancer Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04938297

Collaborator

(none)

100

Enrollment

Location

Arms

55.2

Anticipated Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Central Nervous System Lymphoma	Drug: Rituximab, Lenalidomide, Zanubrutinib Drug: Lenalidomide, Zanubrutinib Drug: Lenalidomide	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 26, 2021

Anticipated Primary Completion Date :

Oct 31, 2022

Anticipated Study Completion Date :

Dec 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Primary CNS Lymphoma，age>65 8 cycles of induction ZR2 , followed by Zanubrutinib or Lenalidomide maintenance for CR/PR fit patients through randomization by 1:1 ration	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. Drug: 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
Experimental: Recurrent/refractory primary CNS lymphoma 8 cycles of induction ZR2, followed by Lenalidomide maintenance for CR/PR fit patients.	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. Drug: Lenalidomide Maintenance therapy: Lenalidomide: 25mg qd (adjusted according to hectogram condition) . Continuously use for 2 years or until disease progression
Experimental: Recurrent/refractory diffuse large B-cell lymphoma with CNS invasion 8 cycles of induction ZR2, followed by Lenalidomide maintenance for CR/PR fit patients.	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. Drug: Lenalidomide Maintenance therapy: Lenalidomide: 25mg qd (adjusted according to hectogram condition) . Continuously use for 2 years or until disease progression

Arm

Intervention/Treatment

Experimental: Primary CNS Lymphoma，age>65

8 cycles of induction ZR2 , followed by Zanubrutinib or Lenalidomide maintenance for CR/PR fit patients through randomization by 1:1 ration

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.

Drug: 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

Experimental: Recurrent/refractory primary CNS lymphoma

8 cycles of induction ZR2, followed by Lenalidomide maintenance for CR/PR fit patients.

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.

Drug: Lenalidomide

Maintenance therapy: Lenalidomide: 25mg qd (adjusted according to hectogram condition) . Continuously use for 2 years or until disease progression

Experimental: Recurrent/refractory diffuse large B-cell lymphoma with CNS invasion

8 cycles of induction ZR2, followed by Lenalidomide maintenance for CR/PR fit patients.

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.

Drug: Lenalidomide

Maintenance therapy: Lenalidomide: 25mg qd (adjusted according to hectogram condition) . Continuously use for 2 years or until disease progression

Outcome Measures

Primary Outcome Measures

Overall response rate [at the end of 8 cycles of induction therapy (each cycle is 28 days)]
To evaluate the overall response rate of ZR2 in the treatment of CNS Lymphoma

Secondary Outcome Measures

Overall response rate [at the end of 4 cycles of induction therapy (each cycle is 28 days) and 1 year of maintenance therapy]
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]
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]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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