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

June 16, 2021 updated by: zhoukeshu, Henan Cancer Hospital
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Henan
      • Zhengzhou, Henan, China
        • Recruiting
        • Henan Cancer Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response rate
Time Frame: 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
at the end of 8 cycles of induction therapy (each cycle is 28 days)

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall response rate
Time Frame: at the end of 4 cycles of induction therapy (each cycle is 28 days) and 1 year of maintenance therapy
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
Time Frame: at the end of 8 cycles of induction therapy (each cycle is 28 days), 1 year and 2 year of maintenance therapy
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
Time Frame: at the end of 8 cycles of induction therapy (each cycle is 28 days), 1 year and 2 year of maintenance therapy
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
Time Frame: at the end of 8 cycles of induction therapy (each cycle is 28 days), 1 year and 2 year of maintenance therapy
at the end of 8 cycles of induction therapy (each cycle is 28 days), 1 year and 2 year of maintenance therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Henan Cancer Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 26, 2021

Primary Completion (Anticipated)

October 31, 2022

Study Completion (Anticipated)

December 31, 2025

Study Registration Dates

First Submitted

June 2, 2021

First Submitted That Met QC Criteria

June 16, 2021

First Posted (Actual)

June 24, 2021

Study Record Updates

Last Update Posted (Actual)

June 24, 2021

Last Update Submitted That Met QC Criteria

June 16, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ZR2 for PCNSL/SCNSL

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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