Diffuse Large B Cell Lymphoma
Conditions
Keywords
LYMPHOMA, DLBCL, ASCT, VENETOCLAX
Brief summary
This single-center, randomized clinical study will evaluate the efficacy and safety of Venetoclax combined with BEAM Pretreatment Regimen in ASCT treatment of DLBCL patients.
Detailed description
Diffuse Large B-cell lymphoma (DLBCL) is a group of highly heterogeneous aggressive non-Hodgkin lymphomas with different pathogenesis and clinical prognosis. Despite the survival benefits of Anthracycline-based chemotherapy bridging autologous stem cell transplantation (ASCT), 30%-40% of DLBCL patients fail to respond to treatment and relapse or die within a short period of time. A phase I/II trial of Venetoclax combined with BEAM as a pretreatment regimen for ASCT of high-risk and relapsed/refractory lymphoma was presented at the ASH Meeting 2021 (NCT03583424), and it studies the side effects and best dose of venetoclax when given together with BEAM (carmustine, etoposide, cytarabine, and melphalan) before stem cell transplant in treating participants with relapsed or refractorynon-Hodgkin lymphoma. The results confirmed that Venetoclax has a good prospect in ASCT.
Interventions
DRUGVenetoclax
100mg day -10, 200mg day -9, 400mg day -8, 800mg day -7 to -1, Given PO
DRUGCarmustine
300mg/m2 day -7, Given IV
DRUGCytarabine
100mg/m2/d, day -6 to day -3, Given IV
DRUGEtoposide
200mg/m2/d, day -6 to day -3, Given IV
DRUGMelphalan
140mg/m2, day -2, Given IV
PROCEDUREHematopoietic Cell Transplantation
Undergo hematopoietic cell transplantation
Sponsors
Ruijin Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. According to world Health Organization (WHO) classification of disease, DLBCL was confirmed by histology, relapsed or refractory after first-line treatment, and CR or PR after upfront treatment; 2. 18≤ age ≤65 years old, male or female; 3. Bcl-2 positive rate \>50% according to immunohistochemistry of biopsied tissue; 4. No serious organic lesions in the main organs, meeting the requirements of the following laboratory examination indicators (conducted within 7 days before treatment) : * White blood cell count ≥3.0×109/L, absolute neutrophil count ≥1.5×109/L, hemoglobin ≥90g/L, platelet ≥75×109/L; * Total bilirubin ≤1.5× upper normal value (ULN); * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5× upper normal value (ULN); * Creatinine clearance was 44-133 mmol/L; 5. ECOG score 0-1; 6. The subject or his/her legal representative must provide written informed consent prior to conducting a special study examination or procedure.
Exclusion criteria
1. Previously received autologous hematopoietic stem cell transplantation; 2. Suffering from serious complications or severe infection; 3. Previously treated with Venetoclax; 4. Central nervous system lymphoma was excluded; Suffering from serious complications or severe infection; 5. A history of other malignant tumors within 5 years, excluding early tumors treated for curative purposes; 6. Patients with uncontrolled cardiovascular and cerebrovascular diseases, coagulation disorders, connective tissue diseases, serious infectious diseases, etc.; 7. HBsAg, HCV or HIV positive. Positive HBV and HCV serology is allowed, but DNA/RNA testing must be negative; 8. Laboratory test value during screening; * Neutrophils \<1.5×109/L; Platelet \<75×109/L; * Bilirubin was 1.5 times higher than the normal upper limit, transaminase was 2.5 times higher than the normal upper limit; * The creatinine level is higher than 1.5 times the upper limit of normal value; 9. Left ventricular ejection fraction ≦ 50%; 10. Other concurrent and uncontrolled medical conditions considered by the investigator would affect the patient's participation in the study; 11. Psychiatric patients or other patients known or suspected to be unable to fully comply with the study protocol; 12. Pregnant or lactating women; 13. The researcher judged that the patients were not suitable for this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival | Baseline up to data cut-off (up to approximately 2 years) | Progression-free survival was defined as the time from the date of ASCT until the date of the first documented day of disease progression or relapse, using 2014 Lugano criteria, or death from an cause, whichever occurred first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | Baseline up to data cut-off (up to approximately 2 years) | Overall survival was defined as the time from the date of ASCT to the date of death from any cause. |
| Complete remission rate | Baseline up to data cut-off (up to approximately 2 years) | Percentage of participants with complete response was determined on 2014 Lugano criteria. |
| The time of hematopoietic reconstruction | Baseline up to data cut-off (up to approximately 2 years) | The first day of neutrophils ≥0.5×109/L for 3 consecutive days was the time of successful implantation of granulocytes. Platelet ≥20.0×109/L for 7 consecutive days and the first day after platelet infusion was considered as the successful time of megakaryocytes implantation. |
| Transplantation-related adverse reactions | Baseline up to data cut-off (up to approximately 2 years) | Transplantation-related adverse reactions are any untoward medical occurrence in a participant which is related to ASCT. |
Contacts
Primary ContactWeili Prof. Zhao
Backup ContactPengpeng Prof. Xu
Outcome results
None listed