Efficacy and Safety of Venetoclax Combined With Dexamethasone and Etoposide in HLH

Phase 1

Recruiting

• Conditions: Hemophagocytic Lymphohistiocytosis
• Interventions: Drug: Venetoclax; Drug: Dexamethasone; Drug: Etoposide

• Registration Number: NCT05546060
• Lead Sponsor: Beijing Friendship Hospital

Brief Summary

This study aimed to investigate the efficacy and safety of venetoclax combined with dexamethasone and etoposide as a salvage therapy for hemophagocytic lymphohistiocytosis.

Detailed Description

Hemophagocytic lymphohistiocytosis (HLH) is a rare and aggressive disease with high mortality and poor prognosis. The HLH-94 and HLH-04 regimens are most commonly used, but approximately 30% of the patients remain unresponsive. Currently, there is no unified evidence-based salvage treatment. There is no unified salvage regimen. This study plans to enroll 20 patients with refractory and recurrent hemophagocytic lymphohistiocytosis. Subjects will receive venetoclax combined with dexamethasone and etoposide for 8 weeks.The safety was evaluated once a week, and the efficacy was evaluated once every 2 weeks. Overall response rate will be evaluated at 8 weeks. Patients were followed up every 3 months thereafter.

Study Timeline

• Study Start: 2022-07-01
• Status Verified: 2022-09
• Study First Submitted: 2022-09-15
• Study First Submitted QC: 2022-09-15
• Last Update Submitted: 2022-09-15
• Study First Posted: 2022-09-19
• Last Update Posted: 2022-09-19
• Primary Completion: 2025-07-01
• Study Completion: 2025-10-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• age ≥18 years old, expected survival time more than 3 months;
• met HLH-2004 diagnostic criteria；
• ECOG score 0-2；
• ECG QTcF interval: male ≤450ms, female ≤470ms;
• AST and ALT ≤3.0 ULN, TB ≤1.5×ULN；serum creatinine≤1.5×ULN，or CrCL ≥ 50mL/min；INR、APTT、PT ≤1.5×ULN；
• without pregnancy or lactation, and agree to contraception during and for at least 6 months after the study；
• signed informed consent.

Exclusion Criteria

• patients with malignancies unrelated to HLH, except for fully recovered non-melanoma skin cancer and carcinoma in situ;
• patients participated in other clinical trials within 4 weeks；
• previously treated with Bcl-2 inhibitors；
• unable to take oral medication；
• history of substance abuse or patients with mental illness；
• severe infection；
• cardiovascular disease，NYHA II-IV；
• allergic to venetoclax or etoposide.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Venetoclax Combined With Dexamethasone and Etoposide	Etoposide	Patients who met the inclusion criteria will receive venetoclax combined with dexamethasone and etoposide for 8 weeks.
Venetoclax Combined With Dexamethasone and Etoposide	Venetoclax	Patients who met the inclusion criteria will receive venetoclax combined with dexamethasone and etoposide for 8 weeks.
Venetoclax Combined With Dexamethasone and Etoposide	Dexamethasone	Patients who met the inclusion criteria will receive venetoclax combined with dexamethasone and etoposide for 8 weeks.

Primary Outcome Measures

Name	Time	Method
Overall response rate	1 year	The percentage of cases with complete response (CR) and partial response (PR) after treatment in the total evaluable cases
Incidence and severity of adverse effects	1 years	The percentage of cases with adverse effects and its severity.

Secondary Outcome Measures

Name	Time	Method
Overall survival	1 years	OS is defined as the time from the initiaion of treatment to death from any cause or July 2025.

Trial Locations

Locations (1)

Beijing Friendship Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China