Efficacy and Safety of Venetoclax Combined With BEAM Pretreatment in Autologous Transplantation for DLBCL

Not Applicable

Not yet recruiting

• Conditions: Diffuse Large B Cell Lymphoma
• Interventions: Drug: Venetoclax; Drug: Carmustine; Drug: Cytarabine; Drug: Etoposide; Procedure: Hematopoietic Cell Transplantation; Drug: Melphalan

• Registration Number: NCT05863845
• Lead Sponsor: Ruijin Hospital

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...

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Status Verified: 2023-05
• Study First Submitted: 2023-05-09
• Study First Submitted QC: 2023-05-09
• Last Update Submitted: 2023-05-09
• Study First Posted: 2023-05-18
• Last Update Posted: 2023-05-18
• Study Start: 2023-06-01
• Primary Completion: 2024-11-30
• Study Completion: 2025-11-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 52

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BEAM	Hematopoietic Cell Transplantation	Patients in this arm will receive BEAM (Carmustine, Etoposide Cytarabine and Melphalan) as Pretreatment Regimen of ASCT. Participants receive Venetoclax PO QD on days -10 to -1, Carmustine IV on day -7, Etoposide IV BID on days -6 to -3, Cytarabine IV BID on days -6 to -3, and Melphalan IV on day -2. Participants then undergo hematopoietic cell transplantation on day 0.
V-BEAM	Venetoclax	Patients in this arm will receive Venetoclax Combined With BEAM (Carmustine, Etoposide Cytarabine and Melphalan) as Pretreatment Regimen of ASCT. Participants receive Venetoclax PO QD on days -10 to -1, Carmustine IV on day -7, Etoposide IV BID on days -6 to -3, Cytarabine IV BID on days -6 to -3, and Melphalan IV on day -2. Participants then undergo hematopoietic cell transplantation on day 0.
V-BEAM	Hematopoietic Cell Transplantation	Patients in this arm will receive Venetoclax Combined With BEAM (Carmustine, Etoposide Cytarabine and Melphalan) as Pretreatment Regimen of ASCT. Participants receive Venetoclax PO QD on days -10 to -1, Carmustine IV on day -7, Etoposide IV BID on days -6 to -3, Cytarabine IV BID on days -6 to -3, and Melphalan IV on day -2. Participants then undergo hematopoietic cell transplantation on day 0.
V-BEAM	Carmustine	Patients in this arm will receive Venetoclax Combined With BEAM (Carmustine, Etoposide Cytarabine and Melphalan) as Pretreatment Regimen of ASCT. Participants receive Venetoclax PO QD on days -10 to -1, Carmustine IV on day -7, Etoposide IV BID on days -6 to -3, Cytarabine IV BID on days -6 to -3, and Melphalan IV on day -2. Participants then undergo hematopoietic cell transplantation on day 0.
V-BEAM	Melphalan	Patients in this arm will receive Venetoclax Combined With BEAM (Carmustine, Etoposide Cytarabine and Melphalan) as Pretreatment Regimen of ASCT. Participants receive Venetoclax PO QD on days -10 to -1, Carmustine IV on day -7, Etoposide IV BID on days -6 to -3, Cytarabine IV BID on days -6 to -3, and Melphalan IV on day -2. Participants then undergo hematopoietic cell transplantation on day 0.
V-BEAM	Cytarabine	Patients in this arm will receive Venetoclax Combined With BEAM (Carmustine, Etoposide Cytarabine and Melphalan) as Pretreatment Regimen of ASCT. Participants receive Venetoclax PO QD on days -10 to -1, Carmustine IV on day -7, Etoposide IV BID on days -6 to -3, Cytarabine IV BID on days -6 to -3, and Melphalan IV on day -2. Participants then undergo hematopoietic cell transplantation on day 0.
V-BEAM	Etoposide	Patients in this arm will receive Venetoclax Combined With BEAM (Carmustine, Etoposide Cytarabine and Melphalan) as Pretreatment Regimen of ASCT. Participants receive Venetoclax PO QD on days -10 to -1, Carmustine IV on day -7, Etoposide IV BID on days -6 to -3, Cytarabine IV BID on days -6 to -3, and Melphalan IV on day -2. Participants then undergo hematopoietic cell transplantation on day 0.
BEAM	Cytarabine	Patients in this arm will receive BEAM (Carmustine, Etoposide Cytarabine and Melphalan) as Pretreatment Regimen of ASCT. Participants receive Venetoclax PO QD on days -10 to -1, Carmustine IV on day -7, Etoposide IV BID on days -6 to -3, Cytarabine IV BID on days -6 to -3, and Melphalan IV on day -2. Participants then undergo hematopoietic cell transplantation on day 0.
BEAM	Etoposide	Patients in this arm will receive BEAM (Carmustine, Etoposide Cytarabine and Melphalan) as Pretreatment Regimen of ASCT. Participants receive Venetoclax PO QD on days -10 to -1, Carmustine IV on day -7, Etoposide IV BID on days -6 to -3, Cytarabine IV BID on days -6 to -3, and Melphalan IV on day -2. Participants then undergo hematopoietic cell transplantation on day 0.
BEAM	Carmustine	Patients in this arm will receive BEAM (Carmustine, Etoposide Cytarabine and Melphalan) as Pretreatment Regimen of ASCT. Participants receive Venetoclax PO QD on days -10 to -1, Carmustine IV on day -7, Etoposide IV BID on days -6 to -3, Cytarabine IV BID on days -6 to -3, and Melphalan IV on day -2. Participants then undergo hematopoietic cell transplantation on day 0.
BEAM	Melphalan	Patients in this arm will receive BEAM (Carmustine, Etoposide Cytarabine and Melphalan) as Pretreatment Regimen of ASCT. Participants receive Venetoclax PO QD on days -10 to -1, Carmustine IV on day -7, Etoposide IV BID on days -6 to -3, Cytarabine IV BID on days -6 to -3, and Melphalan IV on day -2. Participants then undergo hematopoietic cell transplantation on day 0.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.