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

NCT04938297 | Unknown Phase 2

• 1 other identifier: ZR2 for PCNSL/SCNSL
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Central Nervous System Lymphoma

Keywords

Primary CNS Lymphoma; Zanubrutinib; Lenalidomide; Rituximab; Secondary CNS Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

Study Arms (3)

Primary CNS Lymphoma，age>65

EXPERIMENTAL

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; Drug: Lenalidomide, Zanubrutinib

Recurrent/refractory primary CNS lymphoma

EXPERIMENTAL

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

Drug: Rituximab, Lenalidomide, Zanubrutinib; Drug: Lenalidomide

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

EXPERIMENTAL

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

Drug: Rituximab, Lenalidomide, Zanubrutinib; Drug: Lenalidomide

Interventions

Rituximab, Lenalidomide, Zanubrutinib DRUG

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.

Primary CNS Lymphoma，age>65; Recurrent/refractory diffuse large B-cell lymphoma with CNS invasion; Recurrent/refractory primary CNS lymphoma

Lenalidomide, Zanubrutinib DRUG

Maintenance therapy: Lenalidomide: 25mg qd (adjusted according to hectogram condition) or Zanubrutinib 160 mg bid. Continuously use for 2 years or until disease progression

Primary CNS Lymphoma，age>65

Lenalidomide DRUG

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

Recurrent/refractory diffuse large B-cell lymphoma with CNS invasion; Recurrent/refractory primary CNS lymphoma

Eligibility Criteria

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

You may qualify if:

• 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 / 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Henan Cancer Hospital: lead

Study Sites (1)

Henan cancer hospital

Zhengzhou, Henan, China

RECRUITING

MeSH Terms

Interventions

Rituximab; Lenalidomide; zanubrutinib

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Keshu Zhou, Dr.

CONTACT

13674902391; drzhouks77@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Director of Hematology

Study Record Dates

• First Submitted: June 2, 2021
• First Posted: June 24, 2021
• Study Start: May 26, 2021
• Primary Completion: October 31, 2022
• Study Completion: December 31, 2025
• Last Updated: June 24, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)