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A-RGEMOX in the Treatment of Early Relapsed/Refractory DLBCL

Primary Purpose

Diffuse Large B-cell Lymphoma Recurrent, Diffuse Large B Cell Lymphoma Refractory

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Anlotinib hydrochloride, Rituximab, gemcitabine, oxaliplatin
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 Recurrent focused on measuring angiogenesis, anlotinib, early relapse, treatment

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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≥18 years old, ECOG score ≥2 points, both male and female. Histopathologically confirmed as diffuse large B-cell lymphoma, not otherwise specified; 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 Must meet one of the following conditions: Early relapse: response (≥PR) to first-line systemic therapy (including rituximab and anthracyclines) and disease progression within 12 months after the end of treatment; Refractory: first-line treatment includes rituximab and anthracyclines, and no response has been achieved with the most recent systemic treatment (≥PR). 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: 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. Hemophagocytic syndrome at the time of diagnosis. Central nervous system involvement secondary to lymphoma. Participating in other clinical studies, or the first study drug is administered less than 4 weeks after the end of treatment in the previous clinical study. 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 CYP1A2 and CYP3A inhibitors or inducers is required. Patients were excluded if they had taken a strong CYP1A2 and CYP3A inhibitors 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.

Sites / Locations

  • Zhejiang Cancer HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

A+RGEMOX

Arm Description

A-RGEMOX regimen (21 days per cycle, A total of 6 cycles) : Allotinib: 12mg d1~14 po qd, Rituximab: 375mg/m2 d1, gemcitabine: 1000mg/m2 d1 and d8, oxaliplatin: 130mg/m2 d1

Outcomes

Primary Outcome Measures

CRR
Complete Remission Rate

Secondary Outcome Measures

ORR
overall response rate
PFS
Progression Free Survival
OS
Overall Survival
PRR
Partial Remission Rate
AE and SAE
Adverse event and serious adverse event

Full Information

First Posted
September 17, 2023
Last Updated
October 12, 2023
Sponsor
Zhejiang Cancer Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT06086197
Brief Title
A-RGEMOX in the Treatment of Early Relapsed/Refractory DLBCL
Official Title
Prospective, Single-center, Phase II Clinical Study of Anlotinib in Combination With Rituximab,Gemcitabine and Oxaliplatin (A-RGEMOX) in the Treatment of Early Relapsed/Refractory Diffuse Large B-cell Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 15, 2023 (Anticipated)
Primary Completion Date
October 1, 2025 (Anticipated)
Study Completion Date
October 2026 (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

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. However, patients with early relapse (relapse within 12 months since diagnosis or the end of first-line treatment, ER) or primary refractory had an even worse prognosis. Thus, the investigators plan to evaluate the efficacy and safety of anlotinib combined with rituximab, gemcitabine, oxaliplatin (A-RGEMOX) in the treatment of early relapsed/refractory diffuse large B-cell lymphoma.
Detailed Description
Diffuse large B-cell lymphoma (DLBCL), the most common subtype of lymphoma, accounts for about 30%-40% of non-Hodgkin's lymphomas and is highly heterogeneous in terms of clinical presentation and biological behavior. About 10% of patients are resistant to first-line immunochemotherapy, and up to 30%-40% of patients will relapse after treatment. Patients with relapsed/refractory (R/R) DLBCL showed poor prognosis, with a median overall survival of only 6.3 months. Those with early relapse (relapse within 12 months since diagnosis or the end of first-line treatment, ER) or primary refractory had an even worse prognosis. So there is an unmet need for treatment in this population. Previous reports and our unpublished data showed the potential connection between angiogenesis and first-line treatment failure. Accordingly, we assume that the combination of anlotinib and RGEMOX regimen may improve the response rate of patients with early relapsed/refractory DLBCL, increasing the feasibility of follow-up ASCT, and improving long-term survival of this subgroup of 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 Recurrent, Diffuse Large B Cell Lymphoma Refractory
Keywords
angiogenesis, anlotinib, early relapse, treatment

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
A+RGEMOX
Arm Type
Experimental
Arm Description
A-RGEMOX regimen (21 days per cycle, A total of 6 cycles) : Allotinib: 12mg d1~14 po qd, Rituximab: 375mg/m2 d1, gemcitabine: 1000mg/m2 d1 and d8, oxaliplatin: 130mg/m2 d1
Intervention Type
Drug
Intervention Name(s)
Anlotinib hydrochloride, Rituximab, gemcitabine, oxaliplatin
Intervention Description
Anlotinib: 12mg d1~14 po qd, Rituximab: 375mg/m2 d1, gemcitabine: 1000mg/m2 d1 and d8, oxaliplatin: 130mg/m2 d1; For subjects ≥75 years of age, appropriate reduction of chemotherapy drugs (not less than 75% of the standard dose, or withdrawal of day 8 gemcitabine) may be decided by the investigator.
Primary Outcome Measure Information:
Title
CRR
Description
Complete Remission Rate
Time Frame
21days after the end of treatment
Secondary Outcome Measure Information:
Title
ORR
Description
overall response rate
Time Frame
21days after the end of treatment
Title
PFS
Description
Progression Free Survival
Time Frame
From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years
Title
OS
Description
Overall Survival
Time Frame
From date of enrollment until the date of first documented date of death from any cause, assessed up to 5 years
Title
PRR
Description
Partial Remission Rate
Time Frame
21days after the end of treatment
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 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≥18 years old, ECOG score ≥2 points, both male and female. Histopathologically confirmed as diffuse large B-cell lymphoma, not otherwise specified; 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 Must meet one of the following conditions: Early relapse: response (≥PR) to first-line systemic therapy (including rituximab and anthracyclines) and disease progression within 12 months after the end of treatment; Refractory: first-line treatment includes rituximab and anthracyclines, and no response has been achieved with the most recent systemic treatment (≥PR). 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: 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. Hemophagocytic syndrome at the time of diagnosis. Central nervous system involvement secondary to lymphoma. Participating in other clinical studies, or the first study drug is administered less than 4 weeks after the end of treatment in the previous clinical study. 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 CYP1A2 and CYP3A inhibitors or inducers is required. Patients were excluded if they had taken a strong CYP1A2 and CYP3A inhibitors 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
+8617816890591
Email
zjuchenxi@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Haiyan Yang
Phone
0086-571-88122192
Email
yanghy@zjcc.org.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Haiyan Yang
Organizational Affiliation
Zhejiang Cancer Hospital
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

Learn more about this trial

A-RGEMOX in the Treatment of Early Relapsed/Refractory DLBCL

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