Clinical trial NCT05863845: Efficacy and Safety of Venetoclax Combined With BEAM Pretreatment in Autologous Transplantation for DLBCL
Official title: Efficacy and Safety of Venetoclax Combined With BEAM (Carmustine, Etoposide Cytarabine and Melphalan) Pretreatment in Autologous Stem Cell Transplantation for Diffuse Large B-cell Lymphoma: a Single-center, Randomized Clinical Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Diffuse Large B Cell Lymphoma
Keywords: LYMPHOMA
DLBCL
ASCT
VENETOCLAX
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2023-05-18
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression free survival
timeFrame: Baseline up to data cut-off (up to approximately 2 years)
Secondary outcomes:
measure: Overall survival
timeFrame: Baseline up to data cut-off (up to approximately 2 years)
measure: Complete remission rate
timeFrame: Baseline up to data cut-off (up to approximately 2 years)
measure: The time of hematopoietic reconstruction
timeFrame: Baseline up to data cut-off (up to approximately 2 years)
measure: Transplantation-related adverse reactions
timeFrame: Baseline up to data cut-off (up to approximately 2 years)
Other outcomes:
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Study officials:
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