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
1
Location
3
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 DiseaseIntervention/TreatmentPhase
  • 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

ArmIntervention/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

  1. 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

  1. Overall response rate [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 [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 [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 [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:
No
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

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Henan cancer hospitalZhengzhouHenanChina

Sponsors and Collaborators

  • Henan Cancer Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
zhoukeshu, Associate Director of Hematology, Henan Cancer Hospital
ClinicalTrials.gov Identifier:
NCT04938297
Other Study ID Numbers:
  • ZR2 for PCNSL/SCNSL
First Posted:
Jun 24, 2021
Last Update Posted:
Jun 24, 2021
Last Verified:
Jun 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by zhoukeshu, Associate Director of Hematology, Henan Cancer Hospital
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jun 24, 2021