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

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ClinicalTrials.gov Identifier: NCT04938297
Recruitment Status : Recruiting
First Posted : June 24, 2021
Last Update Posted : June 24, 2021
Sponsor:
Information provided by (Responsible Party):
zhoukeshu, Henan Cancer Hospital

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

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Study Type : Interventional  (Clinical Trial)
Estimated 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
Estimated Primary Completion Date : October 31, 2022
Estimated Study Completion Date : December 31, 2025


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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04938297


Contacts
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Contact: Keshu Zhou, Dr. 13674902391 drzhouks77@163.com

Locations
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China, Henan
Henan cancer hospital Recruiting
Zhengzhou, Henan, China
Contact: Keshu Zhou    13674902391    drzhouks77@163.com   
Sponsors and Collaborators
Henan Cancer Hospital
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Responsible Party: zhoukeshu, Associate Director of Hematology, Henan Cancer Hospital
ClinicalTrials.gov Identifier: NCT04938297    
Other Study ID Numbers: ZR2 for PCNSL/SCNSL
First Posted: June 24, 2021    Key Record Dates
Last Update Posted: June 24, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by zhoukeshu, Henan Cancer Hospital:
Primary CNS Lymphoma
Zanubrutinib
Lenalidomide
Rituximab
Secondary CNS Lymphoma
Additional relevant MeSH terms:
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Neoplasms by Histologic Type
Neoplasms
Lymphoma
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Lenalidomide
Zanubrutinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action