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

Sponsor

Beijing Friendship Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05546060

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hemophagocytic Lymphohistiocytosis	Drug: Venetoclax Drug: Dexamethasone Drug: Etoposide	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Efficacy and Safety of Venetoclax Combined With Dexamethasone and Etoposide in the Treatment of Hemophagocytic Lymphohistiocytosis

Actual Study Start Date :

Jul 1, 2022

Anticipated Primary Completion Date :

Jul 1, 2025

Anticipated Study Completion Date :

Oct 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Venetoclax Combined With Dexamethasone and Etoposide Patients who met the inclusion criteria will receive venetoclax combined with dexamethasone and etoposide for 8 weeks.	Drug: Venetoclax Venetoclax 100mg qd d1，200mg qd d2，400mg qd d3-56 Drug: Dexamethasone Dexamethasone 10mg/m2 qd d1-14, 5mg/m2 qd d15-28, 2.5 mg/m2 qd d29-42, and 1.25mg/m2 qd43-56 Drug: Etoposide Etoposide 75mg/m2 qw d1-56

Arm

Intervention/Treatment

Experimental: Venetoclax Combined With Dexamethasone and Etoposide

Patients who met the inclusion criteria will receive venetoclax combined with dexamethasone and etoposide for 8 weeks.

Drug: Venetoclax

Venetoclax 100mg qd d1，200mg qd d2，400mg qd d3-56

Drug: Dexamethasone

Dexamethasone 10mg/m2 qd d1-14, 5mg/m2 qd d15-28, 2.5 mg/m2 qd d29-42, and 1.25mg/m2 qd43-56

Drug: Etoposide

Etoposide 75mg/m2 qw d1-56

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.