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ZR2 Followed by Immunochemotherapy in Elderly Patients With Newly-diagnosed DLBCL

Primary Purpose

Diffuse Large B Cell Lymphoma

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Rituximab, Lenalidomide, Zanubrutinib and RCHOP
Sponsored by
Zhejiang Cancer Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Large B Cell Lymphoma focused on measuring diffuse large B cell lymphoma, elderly, rituximab, lenalidomide, zanubrutinib, treatment, chemo-free

Eligibility Criteria

65 Years - 85 Years (Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Participate in the clinical study voluntarily: fully understand and be informed of the study and sign the informed consent in person; Willing to follow and be able to complete all test procedures.
  2. Age: 70-85 years old, or 65-70 years old with ECOG score ≥2 points, both male and female.
  3. Histopathologically confirmed as diffuse large B-cell lymphoma, not otherwise specified.
  4. No prior anti-tumor therapy, such as chemotherapy, radiotherapy, immunotherapy or biotherapy (tumor vaccine, cytokine, or anti-tumor growth factor).
  5. At least one evaluable or measurable lesion that meets Lugano2014 criteria (evaluable lesion: PET/CT examination showing increased uptake in lymph nodes or extranodal areas (higher than liver) and PET/CT and/or CT consistent with lymphoma; Measurable lesions: nodular lesions >15mm in length or extragendal lesions >10mm in length with increased FDG uptake).
  6. Adequate organ and bone marrow function, no serious hematopoietic dysfunction, abnormal heart, lung, liver, kidney function and immune deficiency (no blood transfusion, granulocytic colony stimulating factor or other relevant medical support within 14 days prior to the use of the study drug) :

    1. neutrophil absolute count (ANC) ≥1.5×109/L (1500/mm3), platelet ≥75×109/L, hemoglobin ≥100g/L (if bone marrow is involved, platelet ≥50×109/L, ANC ≥1.0×109/L, hemoglobin ≥80g/L).
    2. Liver function: serum bilirubin ≤2.5 times the upper limit of normal value, aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤2.5 times the upper limit of normal value (AST or ALT≤5 times the upper limit of normal value is allowed if liver is involved).
    3. Renal function: creatinine clearance ≥60 mL/min (estimated according to the Cockcroft-Gault formula).
    4. Coagulation function: INR≤1.5 times the upper limit of normal value; PT and APTT≤1.5 times the upper limit of normal value.
  7. Left ventricular ejection fraction (LVEF) ≥ 50% in cardiac function examination.
  8. Negative serum pregnancy test and effective contraceptive use from signing informed consent until 6 months after the last chemotherapy.
  9. Life expectancy > 3 months.

Exclusion Criteria:

  1. Pathological subtypes: primary central nervous system diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement, high-grade B-cell lymphoma, not otherwise specified. EBV positive diffuse large B-cell lymphoma
  2. Hemophagocytic syndrome at the time of diagnosis.
  3. Central nervous system involvement secondary to lymphoma.
  4. Participating in other clinical studies.
  5. Medical history of other active malignancy within 2 years prior to enrollment, except for the following conditions:(1) adequately treated in situ of the cervix carcinoma; (2) local basal cell carcinoma or squamous cell carcinoma of skin; (3) Pre-existing malignant disease that is under control and has undergone local radical treatment (surgical or other forms).
  6. History of Human Immunodeficiency Virus (HIV) infection and/or acquired Immunodeficiency syndrome. Patients with positive hepatitis B surface antigen or hepatitis C virus antibody must be tested hepatitis B virus DNA (no more than 1000 iu/ml) and HCV RNA detection (below the detection limit). Patients with hepatitis B virus carriers, or stabilized hepatitis B with anti-virus treatment and cured hepatitis C can be included.
  7. Major surgery was performed within 28 days prior to study initiation.
  8. Any active infection, including bacterial, fungal or viral infections, that requires systemic antiinfection therapy within 14 days prior to treatment.
  9. Accompanied with severe or uncontrolled disease, including symptomatic of congestive heart failure, uncontrolled hypertension, unstable angina, active peptic ulcer or A history of severe hemorrhagic diseases, such as hemophilia A, hemophilia B, von willebrand disease or blood transfusion or other medical intervention history of spontaneous bleeding.
  10. History of stroke or intracranial hemorrhage within 6 months prior to first administration of the study drug.
  11. History of deep vein thrombosis (DVT) or pulmonary embolism (PE) within the past 12 months.
  12. Patients who must take antiplatelet drugs and anticoagulants at the same time due to underlying diseases, and there is no alternative treatment plan.
  13. Continuous treatment with strong and moderate CYP3A inhibitors or CYP3A inducers is required. Patients were excluded if they had taken a CYP3A potent or moderate-acting inhibitor or inducer within 7 days prior to the first administration of the study drug (or had taken these drugs for less than 5 half-lives).
  14. Hypersensitivity to the experimental drug is known.
  15. Patients deemed unsuitable for the study by researchers.

Sites / Locations

  • Zhejiang Cancer HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Rituximab, lenalidomide, zanubrutinib and RCHOP

Arm Description

Rituximab, lenalidomide, zanubrutinib for 2 cycles: rituximab 375mg/m2, d1, lenalidomide 10mg qd d1-10, zanubrutinib 160mg bid. RCHOP for 4 cycles: rituximab 375mg/m2 d0, cyclophosphamide: 750mg/m2 d1, epirubicin: 75mg/m2 d1 (or liposomal doxorubicin 35mg/m2 d1), vindesine 4mg d1, prednisone: 100mg, d1-5.

Outcomes

Primary Outcome Measures

ORR
overall response rate

Secondary Outcome Measures

PFS
Progression Free Survival
OS
Overall Survival
AE and SAE
Adverse event and serious adverse event
Performance status
Assess the patient's performance status according to the Barthel index. Patients will be classified into 5 scales with the score ranging from 0 to 100: 0-20 points=extremely severe functional impairment; 25-45 points=severe functional impairment; 50-70 points=moderate functional impairment; 75-95 points=mild functional impairment; 100 points=normal. Higher scores mean a better outcome.
Life quality
Assess the patient's quality of life according to the EORTC QLQ-C30 questionnaire. Higher scores mean a worse outcome.

Full Information

First Posted
January 28, 2022
Last Updated
October 16, 2023
Sponsor
Zhejiang Cancer Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05290090
Brief Title
ZR2 Followed by Immunochemotherapy in Elderly Patients With Newly-diagnosed DLBCL
Official Title
Prospective, Single-arm, Phase II Clinical Study of Rituximab, Lenalidomide, and Zanubrutinib Combination Regimen Followed by Immunochemotherapy in the Treatment of Elderly Patients With Newly-diagnosed Diffuse Large B-cell Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 1, 2021 (Actual)
Primary Completion Date
June 1, 2024 (Anticipated)
Study Completion Date
December 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Zhejiang Cancer Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
As the most common subtype of lymphoma, diffuse large B-cell lymphoma (DLBCL) is an aggressive but potentially curable malignancy. The poor prognosis of elderly DLBCL patients may be related to the biological behavior of the disease, more comorbidities, poor performance status, and inability to tolerate standard-intensity immunochemotherapy. The investigators plan to use ZR2 regimen(rituximab, lenalidomide and zanubrutinib) for 2 cycles followed by immunochemotherapy for up to 4 cycles in elderly newly diagnosed DLBCL patients.
Detailed Description
DLBCL mostly occurs in the elderly, with a median age at diagnosis of 66 years. Age over 60 years is a poor prognostic factor for DLBCL and is included in the International Prognostic Index (IPI) to stratify patients for prognosis. So there is an unmet need for treatment in this population. Both lenalidomide and BTK inhibitor single drugs have shown certain efficacy in DLBCL patients, and many studies have also explored the effectiveness of rituximab, lenalidomide and BTK inhibitor combination regimen in the treatment of DLBCL. Therefore, the investigators plan to use ZR2 regimen(rituximab, lenalidomide and zanubrutinib) for 2 cycles to reduce tumor burden, improve the patient's physical condition, and improve the tolerance to immunochemotherapy in elderly newly diagnosed DLBCL patients. Up to 4 cycles of immunochemotherapy were then administered sequentially in order to reduce the overall chemotherapy intensity of the patients and improve the long-term quality of life of the patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B Cell Lymphoma
Keywords
diffuse large B cell lymphoma, elderly, rituximab, lenalidomide, zanubrutinib, treatment, chemo-free

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
31 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Rituximab, lenalidomide, zanubrutinib and RCHOP
Arm Type
Experimental
Arm Description
Rituximab, lenalidomide, zanubrutinib for 2 cycles: rituximab 375mg/m2, d1, lenalidomide 10mg qd d1-10, zanubrutinib 160mg bid. RCHOP for 4 cycles: rituximab 375mg/m2 d0, cyclophosphamide: 750mg/m2 d1, epirubicin: 75mg/m2 d1 (or liposomal doxorubicin 35mg/m2 d1), vindesine 4mg d1, prednisone: 100mg, d1-5.
Intervention Type
Drug
Intervention Name(s)
Rituximab, Lenalidomide, Zanubrutinib and RCHOP
Other Intervention Name(s)
BGB-3111
Intervention Description
chemo free period (21 days as a cycle, a total of 2 cycles): rituximab 375mg/m2, d1, lenalidomide 10mg qd d1-10, zanubrutinib 160mg bid. Immunochemotherapy period: RCHOP regimen (21 days as 1 cycle, a total of 4 cycles): rituximab 375mg/m2 d0, cyclophosphamide: 750mg/m2 d1, epirubicin: 75mg/m2 d1 (or liposomal doxorubicin 35mg/m2 d1), vindesine 4mg d1, prednisone: 100mg, d1-5.
Primary Outcome Measure Information:
Title
ORR
Description
overall response rate
Time Frame
21days after the end of treatment
Secondary Outcome Measure Information:
Title
PFS
Description
Progression Free Survival
Time Frame
From date of first day of treatment until the date of first documented progression, assessed up to 24 months
Title
OS
Description
Overall Survival
Time Frame
From date of first day of treatment until the date of first documented date of death from any cause, assessed up to 24 months
Title
AE and SAE
Description
Adverse event and serious adverse event
Time Frame
From date of first day of treatment until 30 day after last treatment
Title
Performance status
Description
Assess the patient's performance status according to the Barthel index. Patients will be classified into 5 scales with the score ranging from 0 to 100: 0-20 points=extremely severe functional impairment; 25-45 points=severe functional impairment; 50-70 points=moderate functional impairment; 75-95 points=mild functional impairment; 100 points=normal. Higher scores mean a better outcome.
Time Frame
At screening period, after 2 cycles of ZR2 regimen(each cycle is 21 days), after 2 cycles of RCHOP regimen(each cycle is 21 days) and 21days after the end of treatment
Title
Life quality
Description
Assess the patient's quality of life according to the EORTC QLQ-C30 questionnaire. Higher scores mean a worse outcome.
Time Frame
At screening period, after 2 cycles of ZR2 regimen(each cycle is 21 days), after 2 cycles of RCHOP regimen(each cycle is 21 days) and 21days after the end of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participate in the clinical study voluntarily: fully understand and be informed of the study and sign the informed consent in person; Willing to follow and be able to complete all test procedures. Age: 70-85 years old, or 65-70 years old with ECOG score ≥2 points, both male and female. Histopathologically confirmed as diffuse large B-cell lymphoma, not otherwise specified. No prior anti-tumor therapy, such as chemotherapy, radiotherapy, immunotherapy or biotherapy (tumor vaccine, cytokine, or anti-tumor growth factor). At least one evaluable or measurable lesion that meets Lugano2014 criteria (evaluable lesion: PET/CT examination showing increased uptake in lymph nodes or extranodal areas (higher than liver) and PET/CT and/or CT consistent with lymphoma; Measurable lesions: nodular lesions >15mm in length or extragendal lesions >10mm in length with increased FDG uptake). Adequate organ and bone marrow function, no serious hematopoietic dysfunction, abnormal heart, lung, liver, kidney function and immune deficiency (no blood transfusion, granulocytic colony stimulating factor or other relevant medical support within 14 days prior to the use of the study drug) : neutrophil absolute count (ANC) ≥1.5×109/L (1500/mm3), platelet ≥75×109/L, hemoglobin ≥100g/L (if bone marrow is involved, platelet ≥50×109/L, ANC ≥1.0×109/L, hemoglobin ≥80g/L). Liver function: serum bilirubin ≤2.5 times the upper limit of normal value, aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤2.5 times the upper limit of normal value (AST or ALT≤5 times the upper limit of normal value is allowed if liver is involved). Renal function: creatinine clearance ≥60 mL/min (estimated according to the Cockcroft-Gault formula). Coagulation function: INR≤1.5 times the upper limit of normal value; PT and APTT≤1.5 times the upper limit of normal value. Left ventricular ejection fraction (LVEF) ≥ 50% in cardiac function examination. Negative serum pregnancy test and effective contraceptive use from signing informed consent until 6 months after the last chemotherapy. Life expectancy > 3 months. Exclusion Criteria: Pathological subtypes: primary central nervous system diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement, high-grade B-cell lymphoma, not otherwise specified. EBV positive diffuse large B-cell lymphoma Hemophagocytic syndrome at the time of diagnosis. Central nervous system involvement secondary to lymphoma. Participating in other clinical studies. Medical history of other active malignancy within 2 years prior to enrollment, except for the following conditions:(1) adequately treated in situ of the cervix carcinoma; (2) local basal cell carcinoma or squamous cell carcinoma of skin; (3) Pre-existing malignant disease that is under control and has undergone local radical treatment (surgical or other forms). History of Human Immunodeficiency Virus (HIV) infection and/or acquired Immunodeficiency syndrome. Patients with positive hepatitis B surface antigen or hepatitis C virus antibody must be tested hepatitis B virus DNA (no more than 1000 iu/ml) and HCV RNA detection (below the detection limit). Patients with hepatitis B virus carriers, or stabilized hepatitis B with anti-virus treatment and cured hepatitis C can be included. Major surgery was performed within 28 days prior to study initiation. Any active infection, including bacterial, fungal or viral infections, that requires systemic antiinfection therapy within 14 days prior to treatment. Accompanied with severe or uncontrolled disease, including symptomatic of congestive heart failure, uncontrolled hypertension, unstable angina, active peptic ulcer or A history of severe hemorrhagic diseases, such as hemophilia A, hemophilia B, von willebrand disease or blood transfusion or other medical intervention history of spontaneous bleeding. History of stroke or intracranial hemorrhage within 6 months prior to first administration of the study drug. History of deep vein thrombosis (DVT) or pulmonary embolism (PE) within the past 12 months. Patients who must take antiplatelet drugs and anticoagulants at the same time due to underlying diseases, and there is no alternative treatment plan. Continuous treatment with strong and moderate CYP3A inhibitors or CYP3A inducers is required. Patients were excluded if they had taken a CYP3A potent or moderate-acting inhibitor or inducer within 7 days prior to the first administration of the study drug (or had taken these drugs for less than 5 half-lives). Hypersensitivity to the experimental drug is known. Patients deemed unsuitable for the study by researchers.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
xi chen
Phone
17816890591
Email
zjuchenxi@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Haiyan Yang
Organizational Affiliation
Zhejiang Cancer Hospital, Hangzhou, China
Official's Role
Principal Investigator
Facility Information:
Facility Name
Zhejiang Cancer Hospital
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310022
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Haiyan Yang, PhD
Phone
0086-571-88122192
Email
yanghy@zjcc.org.cn
First Name & Middle Initial & Last Name & Degree
Xi Chen, MD
Phone
0086-571-88122192
Email
zjuchenxi@126.com
First Name & Middle Initial & Last Name & Degree
Xi Chen, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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ZR2 Followed by Immunochemotherapy in Elderly Patients With Newly-diagnosed DLBCL

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