Clinical Trials /

Toripalimab in Combination With R-CHOP for Elderly Patients With Untreated Diffused B Cell Lymphoma

NCT04058470

Description:

This study will research untreated elderly diffuse large B cell lymphoma patients respond and safty to toripalimab combined with R-CHOP chemotherapy regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) therapy.

Related Conditions:
  • ALK-Positive Large B-Cell Lymphoma
  • Central Nervous System Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • Grade 3b Follicular Lymphoma
  • High Grade B-Cell Lymphoma, Not Otherwise Specified
  • Transformed Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Toripalimab in Combination With R-CHOP for Elderly Patients With Untreated Diffused B Cell Lymphoma
  • Official Title: Phase Ib/II Study of Toripalimab In Combination With R-CHOP Regimen (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone) for Elderly Naïve Patients With Diffuse Large B-cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: TREND
  • NCT ID: NCT04058470

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

Interventions

DrugSynonymsArms
ToripalimabJS001TR-CHOP
R-CHOP ProtocolRituximab,Cyclophosphamide,Doxorubicin,Vincristine,PrednisoneTR-CHOP

Purpose

This study will research untreated elderly diffuse large B cell lymphoma patients respond and safty to toripalimab combined with R-CHOP chemotherapy regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) therapy.

Trial Arms

NameTypeDescriptionInterventions
TR-CHOPExperimentalTR-CHOP: Toripalimab,Rituximab,Cyclophosphamide,Doxorubicin,Vincristine,Prednisone
  • Toripalimab
  • R-CHOP Protocol

Eligibility Criteria

        Inclusion Criteria:

          1. 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;

          2. Aged 60-75 years old male or female;

          3. Untreated,without any anti-lymphoma treatment;

          4. DLBCL, or follicular lymphoma grade 3B, or transformed DLBCL, EBV (+) DLBCL, ALK (+)
             DLBCL, high-grade lymphoma were confirmed by histopathology examination;

          5. Clinical stage II-IV, or stage I with bulky diesase (diameter > 7.5 cm);

          6. International Prognostic Score (IPI): 2-5;

          7. Paraffin tissue specimens or fresh puncture tissue specimens are available;

          8. Eastern cooperative oncology group score: 0-2;

          9. Estimated survival ≥ 12 months;

         10. There must be at least one evaluate able or measurable lesion that meets the LYRIC
             2016 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;

         11. 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%);

         12. There was no evidence that subjects had difficulty breathing at rest, and the measured
             value of pulse oximetry at rest was more than 92%;

         13. 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;

         14. 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.

        Exclusion Criteria:

          1. Primary central nervous system lymphoma or secondary central nervous system
             involvement;

          2. Hemophagocytic syndrome;

          3. Previously treated with immunological checkpoint inhibitors (PD-1, PD-L1, CTLA-4,
             etc.);

          4. History of severe allergies or allergic reactions to humanized or murine monoclonal
             antibodies;

          5. 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;

          6. 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);

          7. 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;

          8. 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.;

          9. The study began with major surgery within 28 days before treatment or radiotherapy
             within 90 days before treatment;

         10. Start the study and receive Chinese herbal medicine or Chinese patent medicine
             treatment within 7 days before treatment;

         11. Begin research on live vaccination (except influenza attenuated vaccine) within 28
             days before treatment;

         12. History of human immunodeficiency virus (HIV) infection and/or patients with acquired
             immunodeficiency syndrome are known;

         13. 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;

         14. Start studying any active infections requiring systemic anti-infective treatment
             within 14 days of treatment.

         15. Pregnant or lactating women;

         16. People with known history of alcoholism or drug abuse;

         17. Have uncontrollable complications, including but not limited to symptomatic congestive
             heart failure, uncontrollable hypertension, unstable angina, active peptic ulcer or
             hemorrhagic diseases;

         18. History of interstitial lung disease or non-infectious pneumonia. Subjects who had
             previously had non-infectious pneumonia caused by drugs or radiation but had no
             symptoms were allowed to enter the group;

         19. The QTcF interval is more than 450 msec, unless it is secondary to bundle branch
             block;

         20. Past psychiatric history; incapacitated or restricted;

         21. According to the researchers' judgment, patients' underlying condition may increase
             their risk of receiving research drug treatment, or confuse their judgment on toxic
             reactions;

         22. Other researchers consider it unsuitable for patients to participate in this study.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:60 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (ORR), Investigator-Assessed
Time Frame:upto 36 months
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Progression-Free Survival (PFS)
Time Frame: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
Safety Issue:
Description:Statistical analysis will entail descriptive statistics, and survival analysis including Kaplan-Meier estimates, log-rank testing of univariate prognostic factors, Cox proportional hazards analysis, as well as T-testing and regression analysis for comparing continuous variables in correlative study data.
Measure:Overall survival(OS)
Time Frame:OS is defined as the time from the treatment date to the death from any cause up to 60 months
Safety Issue:
Description:Statistical analysis will entail descriptive statistics, and survival analysis including Kaplan-Meier estimates, log-rank testing of univariate prognostic factors, Cox proportional hazards analysis, as well as T-testing and regression analysis for comparing continuous variables in correlative study data.
Measure:Percentage of Participants With Adverse Events (AEs)
Time Frame:Up to 36 months
Safety Issue:
Description:An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Huiqiang Huang

Trial Keywords

  • DLBCL,HGL

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