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

May 9, 2023 updated by: Zhao Weili, Ruijin Hospital

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

52

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Procedure: Hematopoietic Cell Transplantation
Undergo hematopoietic cell transplantation
Drug: Venetoclax
100mg day -10, 200mg day -9, 400mg day -8, 800mg day -7 to -1, Given PO
Drug: Carmustine
300mg/m2 day -7, Given IV
Drug: Cytarabine
100mg/m2/d, day -6 to day -3, Given IV
Drug: Etoposide
200mg/m2/d, day -6 to day -3, Given IV
Drug: Melphalan
140mg/m2, day -2, Given IV
Sham Comparator: 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.
Procedure: Hematopoietic Cell Transplantation
Undergo hematopoietic cell transplantation
Drug: Carmustine
300mg/m2 day -7, Given IV
Drug: Cytarabine
100mg/m2/d, day -6 to day -3, Given IV
Drug: Etoposide
200mg/m2/d, day -6 to day -3, Given IV
Drug: Melphalan
140mg/m2, day -2, Given IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival
Time Frame: 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.
Baseline up to data cut-off (up to approximately 2 years)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 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.
Baseline up to data cut-off (up to approximately 2 years)
Complete remission rate
Time Frame: Baseline up to data cut-off (up to approximately 2 years)
Percentage of participants with complete response was determined on 2014 Lugano criteria.
Baseline up to data cut-off (up to approximately 2 years)
The time of hematopoietic reconstruction
Time Frame: 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.
Baseline up to data cut-off (up to approximately 2 years)
Transplantation-related adverse reactions
Time Frame: 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.
Baseline up to data cut-off (up to approximately 2 years)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ruijin Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

June 1, 2023

Primary Completion (Anticipated)

November 30, 2024

Study Completion (Anticipated)

November 30, 2025

Study Registration Dates

First Submitted

May 9, 2023

First Submitted That Met QC Criteria

May 9, 2023

First Posted (Actual)

May 18, 2023

Study Record Updates

Last Update Posted (Actual)

May 18, 2023

Last Update Submitted That Met QC Criteria

May 9, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • V-BEAM

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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