Phase Ib/II Study of Toripalimab In Combination With Rituximab Followed by R-CHOP Regimen (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone) for Elderly Naïve Patients With Diffuse Large B-cell Lymphoma
Overview
- Phase
- Phase 1
- Intervention
- Toripalimab, Rituximab
- Conditions
- Diffuse Large B Cell Lymphoma
- Sponsor
- Huiqiang Huang
- Enrollment
- 140
- Locations
- 1
- Primary Endpoint
- Overall Response Rate (ORR) of toripalimab combined with Rituximab , Investigator-Assessed
- Status
- Recruiting
- Last Updated
- 4 years ago
Overview
Brief Summary
- 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.
- 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.
Detailed Description
The study consisted of a phase I and II portion. In phase I, patients accepted at least 2 cycles of toripalimab plus rituximab. Another 2 cycles of toripalimab plus rituximab will offered if they achieved CR. In phase II, all patients accpet R-CHOP regimen. If patient get CR after, they will accept 4 cycles of R-CHOP regimen, patients with PR,SD or PD will accept 6 cycles of R-CHOP.
Investigators
Huiqiang Huang
professor
Sun Yat-sen University
Eligibility Criteria
Inclusion Criteria
- •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;
Exclusion Criteria
- •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;
Arms & Interventions
TR follow by R-CHOP
TR follow by R-CHOP: TR: Toripalimab,Rituximab, R-CHOP: Rituximab, Cyclophosphamide,Doxorubicin,Vincristine,Prednisone
Intervention: Toripalimab, Rituximab
TR follow by R-CHOP
TR follow by R-CHOP: TR: Toripalimab,Rituximab, R-CHOP: Rituximab, Cyclophosphamide,Doxorubicin,Vincristine,Prednisone
Intervention: R-CHOP Protocol
Outcomes
Primary Outcomes
Overall Response Rate (ORR) of toripalimab combined with Rituximab , Investigator-Assessed
Time Frame: upto 36 months
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.
Overall Response Rate (ORR) of toripalimab combined with Rituximab followed by R-CHOP regimen, Investigator-Assessed
Time Frame: upto 36 months
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.
The optimal dosage of Toripalimab combined with Rituximab
Time Frame: upto 6 months
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.
Secondary Outcomes
- 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)
- Percentage of Participants With Adverse Events (AEs)(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)