Toripalimab Plus Rituximab Followed by R-CHOP for Elderly Patients With Untreated Diffused B Cell Lymphoma

NCT04058470 | Unknown Phase 1

• 1 other identifier: TREND
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

1. 1.Phase I portion of this study will evaluate the efficacy and saftey of toripalimab plus rituximab in treating untreated elderly diffuse large B cell lymphoma patients.
2. 2.The aim of phase II portion of this study will evaluate the efficacy and saftey of toripalimab plus rituximab followed by R-CHOP(rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) regimen in treating untreated elderly diffuse large B cell lymphoma patients.

Conditions

Diffuse Large B Cell Lymphoma; High-grade B-cell Lymphoma; Follicular Lymphoma Grade IIIb; Transformed Lymphoma; EBV-Positive DLBCL, Nos; ALK-Positive Anaplastic Large Cell Lymphoma

Keywords

DLBCL,HGL

Outcome Measures

Primary Outcomes (3)

• Overall Response Rate (ORR) of toripalimab combined with Rituximab , Investigator-Assessed

  Overall response was determined on the basis of investigator assessments according to the Lymphoma response to immunomodulatory therapy criteria (LYRIC) for Malignant Lymphoma, 2016. Tumor assessments were performed with CT/MRI with or without PET. Overall response was defined as the disappearance of all evidence of disease, regression of measurable disease, and no new sites.

  upto 36 months

• The optimal dosage of Toripalimab combined with Rituximab

  Maximum tolerable dose（MTD）and dose-limiting toxicity（DLT）of Toripalimab will be conducted in Phase Ib clinical studies. MTD and DLT is defined as protocol-defined Toripalimab related events.

  upto 6 months

• Overall Response Rate (ORR) of toripalimab combined with Rituximab followed by R-CHOP regimen, Investigator-Assessed

  Overall response was determined on the basis of investigator assessments according to the Lymphoma response to immunomodulatory therapy criteria (LYRIC) for Malignant Lymphoma, 2016. Tumor assessments were performed with CT/MRI with or without PET. Overall response was defined as the disappearance of all evidence of disease, regression of measurable disease, and no new sites.

  upto 36 months

Secondary Outcomes (3)

• Progression-Free Survival (PFS)

  Time from diagnosis until relapse or progression, non-protocol re-treatment of lymphoma, or death as a result of any cause, assessed up to 36 months

• Overall survival(OS)

  OS is defined as the time from the treatment date to the death from any cause up to 60 months

• Percentage of Participants With Adverse Events (AEs)

  Up to 36 months

Study Arms (1)

TR follow by R-CHOP

EXPERIMENTAL

TR follow by R-CHOP: TR: Toripalimab,Rituximab, R-CHOP: Rituximab, Cyclophosphamide,Doxorubicin,Vincristine,Prednisone

Drug: Toripalimab, Rituximab; Drug: R-CHOP Protocol

Interventions

Toripalimab, Rituximab DRUG

Toripalimab in combination with Rituximab will be administered every 3 weeks up to 4 cycles.

Also known as: JS001, Rituximab

TR follow by R-CHOP

R-CHOP Protocol DRUG

After toripalimab plus rituximab treatment, R-CHOP regimen will be administered every 3 weeks in combination with R-CHOP up to 6 cycles.

Also known as: Rituximab,Cyclophosphamide,Doxorubicin,Vincristine,Prednisone

TR follow by R-CHOP

Eligibility Criteria

• Age: 60 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Volunteer to participate in clinical research; fully understand and know the research and sign the Informed Consent Form (ICF); willing to follow and have the ability to complete all trial procedures;
• Aged 60-75 years old male or female;
• Untreated,without any anti-lymphoma treatment;
• DLBCL, or follicular lymphoma grade 3B, or transformed DLBCL, EBV (+) DLBCL, ALK (+) DLBCL, high-grade lymphoma were confirmed by histopathology examination;
• Clinical stage II-IV, or stage I with bulky diesase (diameter \> 7.5 cm);
• International Prognostic Score (IPI): 2-5;
• Paraffin tissue specimens or fresh puncture tissue specimens are available;
• Eastern cooperative oncology group score: 0-2;
• Estimated survival ≥ 12 months;
• There must be at least one evaluate able or measurable lesion that meets the Lugano 2014 Lymphoma criteria \[evaluable lesion: 18F-fluorodeoxyglucose/Positron Emission Tomography (18FDG/PET) examination showing increased lymph node or extranodal uptake (higher than liver) and PET and/or computed tomography (Computed Tomography) CT) features are consistent with lymphoma findings; lesions can be measured: nodular lesions \> 15mm or extranodal lesions \> 10mm (if the only measurable lesion has received radiotherapy in the past, there must be evidence of radiological progress after radiotherapy), and accompanied by increased 18FDG uptake). Except for this, there is no measurable increase in diffuse 18FDG uptake in the liver;
• Adequate organ and bone marrow function, no severe hematopoietic dysfunction, cardiac, pulmonary, liver, kidney, thyroid dysfunction and immune deficiency (no blood transfusion, granulocyte colony stimulating factor or other medical support was received within 14 days prior to the use of the research drug): 1) The absolute value of neutrophils (\>1.5×10\^9/L); 2) platelet count (\> 75×10\^9/L); 3) Hemoglobin (\> 9 g/dL); 4) Upper Limit Normal (ULN) or creatinine clearance rate (\>40 mL/min) of serum creatinine (\<1.5 times normal value upper limit) (estimated by Cockcroft-Gault formula); 5) Serum total bilirubin \< 1.5 times ULN; 6) Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) = 2.5 times ULN; 7) Coagulation function: International Normalized Ratio (INR) = 1.5 times ULN; Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) = 1.5 times ULN (unless the subject is receiving anticoagulant therapy and PT and APTT are using anticoagulant therapy at screening time). Within the expected range; 8) Thyrotropin (TSH) or free thyroxine (FT4) or free triiodothyronine (FT3) were all within the normal range (+10%);
• There was no evidence that subjects had difficulty breathing at rest, and the measured value of pulse oximetry at rest was more than 92%;
• Participants must pass a pulmonary function test (PFT) to confirm that forced expiratory volume (FEV1)/forced vital capacity (FVC) in the first second is more than 60%, unless it is a large mediastinal mass caused by lymphoma that cannot meet this standard; carbon monoxide diffusion (DLCO), FEV1 and FVC are all above 50% of the predicted value; all PFT results must be obtained within four weeks before the first administration;
• Women of Childbearing Potential (WOBCP) must undergo a serum pregnancy test within seven days before the first medication and the results are negative. WOBCP or men and their WOBCP partners should agree to take effective contraceptive measures from the signing of ICF until six months after the last dose of the research drug is used.

You may not qualify if:

• Primary central nervous system lymphoma or secondary central nervous system involvement;
• Hemophagocytic syndrome;
• Previously treated with immunological checkpoint inhibitors (PD-1, PD-L1, CTLA-4, etc.);
• History of severe allergies or allergic reactions to humanized or murine monoclonal antibodies;
• Patients with active autoimmune diseases requiring systematic treatment in the past two years (hormone replacement therapy is not considered systematic treatment, such as type I diabetes mellitus, hypothyroidism requiring only thyroxine replacement therapy, adrenocortical dysfunction or pituitary dysfunction requiring only physiological doses of glucocorticoid replacement therapy); Patients with autoimmune diseases who do not require systematic treatment within two years can be enrolled;
• Begin the study on subjects requiring systemic glucocorticoid therapy or other immunosuppressive therapy for a given condition within 14 days before treatment \[allowing subjects to use local, ocular, intra-articular, intranasal and inhaled glucocorticoid therapy (with very low systemic absorption); and allowing short-term (\< 7 days) glucocorticoid prophylaxis (e.g., contrast agent overdose) Sensitivity) or for the treatment of non-autoimmune diseases (e.g. delayed hypersensitivity caused by contact allergens), except for tumor reduction due to large tumor burden (prednisone 30mg, bid × 5 days or equivalent dose of other glucocorticoid therapy);
• In the past five years, patients with other malignant tumors have undergone radical treatment, except for basal cell carcinoma of skin, squamous cell carcinoma of skin, carcinoma in situ of breast and carcinoma in situ of cervix;
• Begin the study and receive systemic antineoplastic therapy within 28 days before treatment, including chemotherapy, immunotherapy, biotherapy (cancer vaccine, cytokines, or growth factors that control cancer), etc.;
• The study began with major surgery within 28 days before treatment or radiotherapy within 90 days before treatment;
• Start the study and receive Chinese herbal medicine or Chinese patent medicine treatment within 7 days before treatment;
• Begin research on live vaccination (except influenza attenuated vaccine) within 28 days before treatment;
• History of human immunodeficiency virus (HIV) infection and/or patients with acquired immunodeficiency syndrome are known;
• Patients with active hepatitis B or active hepatitis C. Patients who are positive for hepatitis B Surface Antigen (HBsAg) or hepatitis C Virus (HCV) antibodies at screening stage must pass further detection of hepatitis B Virus (HBV) DNA titer (no more than 2500 copies/mL or 500 IU/mL) and HCV RNA (no more than the lower limit of the detection method) in the row. In addition to active hepatitis B or hepatitis C infections requiring treatment, group trials can be conducted. Hepatitis B carriers, stable hepatitis B (DNA titer should not be higher than 2500 copies/mL or 500 IU/mL) after drug treatment, and cured hepatitis C patients can be enrolled in the group; 19. Patients with active pulmonary tuberculosis;
• Start studying any active infections requiring systemic anti-infective treatment within 14 days of treatment.
• Pregnant or lactating women;

Sponsors & Collaborators

• Huiqiang Huang: lead

Study Sites (1)

Department of hematology department, Nanfang hospital

Guangzhou, Guangdong, 510515, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Pyloric Stenosis, Hypertrophic

Interventions

toripalimab; Rituximab; R-CHOP protocol

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Pyloric Stenosis; Gastric Outlet Obstruction; Stomach Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Huiqiang Huang, Professor

CONTACT

+86 020 87343350; huanghq@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: August 13, 2019
• First Posted: August 15, 2019
• Study Start: April 24, 2020
• Primary Completion: December 30, 2023
• Study Completion: December 30, 2025
• Last Updated: April 14, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)