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

NCT ID: NCT05863845

Last Updated: 2023-05-18

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-01
• Study Completion Date: 2025-11-30

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.

Conditions

Diffuse Large B Cell Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

V-BEAM

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.

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

100mg day -10, 200mg day -9, 400mg day -8, 800mg day -7 to -1, Given PO

Carmustine

Intervention Type: DRUG

300mg/m2 day -7, Given IV

Cytarabine

Intervention Type: DRUG

100mg/m2/d, day -6 to day -3, Given IV

Etoposide

Intervention Type: DRUG

200mg/m2/d, day -6 to day -3, Given IV

Melphalan

Intervention Type: DRUG

140mg/m2, day -2, Given IV

Hematopoietic Cell Transplantation

Intervention Type: PROCEDURE

Undergo hematopoietic cell transplantation

BEAM

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.

Group Type: SHAM_COMPARATOR

Carmustine

Intervention Type: DRUG

300mg/m2 day -7, Given IV

Cytarabine

Intervention Type: DRUG

100mg/m2/d, day -6 to day -3, Given IV

Etoposide

Intervention Type: DRUG

200mg/m2/d, day -6 to day -3, Given IV

Melphalan

Intervention Type: DRUG

140mg/m2, day -2, Given IV

Hematopoietic Cell Transplantation

Intervention Type: PROCEDURE

Undergo hematopoietic cell transplantation

Interventions

Venetoclax

100mg day -10, 200mg day -9, 400mg day -8, 800mg day -7 to -1, Given PO

Intervention Type: DRUG

Carmustine

300mg/m2 day -7, Given IV

Intervention Type: DRUG

Cytarabine

100mg/m2/d, day -6 to day -3, Given IV

Intervention Type: DRUG

Etoposide

200mg/m2/d, day -6 to day -3, Given IV

Intervention Type: DRUG

Melphalan

140mg/m2, day -2, Given IV

Intervention Type: DRUG

Hematopoietic Cell Transplantation

Undergo hematopoietic cell transplantation

Intervention Type: PROCEDURE

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ruijin Hospital

OTHER

Sponsor Role: lead

Responsible Party

Zhao Weili

Prof.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Weili Prof. Zhao

Role: CONTACT

zwl_trial@163.com

+862164370045 ext. 610707

Pengpeng Prof. Xu

Role: CONTACT

pengpeng_xu@126.com

+862164370045

Other Identifiers

V-BEAM

Identifier Type: -

Identifier Source: org_study_id