DLBCL
Conditions
Brief summary
This is a prospective, single-arm, multi-center, phase II clinical study to evaluate the efficacy and safety of Trilaciclib in DLBCL patients treated with R-CHOP.
Detailed description
This is a prospective, single-arm, multi-center, phase II clinical study to investigate the myeloprotection efficacy, antitumor efficacy, and safety of Trilaciclib in DLBCL patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin or Epirubicin, vincristine, and prednisone). 38 eligible subjects who met the inclusion criteria were screened and given a treatment regimen of Trilaciclib before chemotherapy R-CHOP, after signing informed consent. The incidence of Grade ≥ 3 neutropenia was used as the primary endpoint to observe whether Trilaciclib could reduce the occurrence or degree of chemotherapy-induced myelosuppression (CIM). Researchers will monitor potential adverse events (AEs) throughout the entire trial and grade the severity of adverse events according to the guidelines of the National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) 5.0.
Interventions
DRUGTrilaciclib+R-CHOP
This is a prospective, single-arm, multi-center, phase II clinical study to evaluate the efficacy and safety of Trilaciclib in DLBCL patients treated with R-CHOP.
Sponsors
Sun Yat-sen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Having sufficient understanding of this study and being willing to sign the informed consent form (ICF); 2. Age above 18 years old (including 18 years old)，regardless of gender; 3. Treatment-naive, histologically confirmed DLBCL, at least one tumor lesion that could be measured accurately at baseline according to RECIST1.1 criteria; 4. IPI score 0-2; 5. ECOG score of 0-2； 6. No prophylactic G-CSF, TPO, IL-11, ESA, iron within 1 week of screening hematology test, and no platelet transfusion or blood transfusion； 7. Estimated survival greater than 3 months； 8. Adequate organ function； 9. Being willing and able to comply with the visits, treatment plan, laboratory examinations and other study procedures scheduled in the study; 10. Women of childbearing potential must undergo a serum pregnancy test within 3 days prior to the first dose and the result must be negative. Female patients of childbearing potential and male subjects whose partners are women of childbearing potential must agree to use highly effective contraceptive methods during the study period and within 3 months after the last dose of study drug.
Exclusion criteria
1. The subject is participating in other interventional clinical studies; 2. The subject has previous or concurrent other malignancies; 3. Lymphoma bone marrow invasion; 4. The presence of symptomatic brain metastases requiring immediate radiotherapy or steroid therapy; 5. Known hypersensitivity to the applied drugs or any excipients； 6. Previous hematopoietic stem cell or bone marrow transplantation； 7. Active infection requiring systemic treatment; 8. Patients with uncontrolled cardiac clinical symptoms or diseases; 9. The subject has severe active infection or unexplained fever \> 38.5 degrees during screening or before the first dose (the subject can be enrolled due to tumor fever as judged by the investigator); 10. Radiotherapy or radiotherapy at any site within 2 weeks before study medication; 11. Any investigational drug within 4 weeks before study medication; 12. Live attenuated vaccine within 4 weeks before study medication or possibly during the study period, influenza vaccine can be administered during the influenza season; 13. Pregnant or lactating women; 14. Any reasons that the investigator believes that it should be excluded from this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Grade 3/4 neutropenia | Up to 6 months | Proportion of subjects with at least one absolute neutrophil count (ANC) \< 1.0 × 10\^9/L enrolled and treated with at least one dose of trilaciclib |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR | Up to 6 months | Objective Response Rate (ORR) is defined as the percentage of participants achieving complete response (CR) and partial response (PR) for tumor volume reduction and maintaining the minimum duration requirement based on RECIST v1.1 |
| 2y-PFS | Up to 2 years | Progression-free survival (PFS per RECIST 1.1) is defined as the time until the first imaging disease progression or death (whichever occurs first) |
| 2y-OS | Up to 2 years | Overall survival (OS) is defined as the time until the subject's death due to any reason |
| Neutrophil-related myeloprotection efficacy | Up to 6 months | Occurrence of febrile neutropenia adverse events(AEs) |
| Platelet related myeloprotection efficacy | Up to 6 months | Occurrence of Grade 3/4 decrease of platelets |
| Myeloprotection efficacy | Up to 6 months | Hospitalization due to chemotherapy-induced myelosuppression |
| Chemotherapy dosing | Up to 6 months | Chemotherapy dose reductions and delays due to chemotherapy-induced myelosuppression |
| Incidence of Treatment-Emergent Adverse Events | Up to 6 months | To assess the effects of trilaciclib administered prior to chemotherapy on the occurrence and severity of adverse events by CTCAE 5.0, study treatment discontinuation due to adverse events, and trilaciclib adverse events of special interest. |
| RBC related myeloprotection efficacy | Up to 6 months | Occurrence of Grade 3/4 decrease of hemoglobin, occurrence and number of RBC transfusions on/after Week 5 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory analysis of potential biomarkers related with the outcome | Up to 6 months | The change from baseline in immune cell levels in peripheral blood after treatment includes, but is not limited to: T cells (CD3, CD4, and CD8) B cells (CD19) Effector T cells (IFN-γ-producing CD4+ T cells, IL-2-producing CD4+ T cells, IL-17-producing CD4+ T cells, IFN-γ-producing CD8+ T cells, IL-2-producing CD8+ T cells) T cell activation markers (HLA-DR+ CD4+ T cells, HLA-DR+ CD8+ T cells) Regulatory T cells (Treg cells) (FoxP3, CD25, and CD127) Proportion of cells in the S phase |
Countries
China
Outcome results
None listed