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

Hemophagocytic Lymphohistiocytosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05546060
• Other study ID #: BFH20220425006/BFHHZS20220026
• Status: Recruiting
• Phase: Phase 1
• Start date: July 1, 2022
• Est. completion date: October 1, 2025

Study information

• Verified date: September 2022
• Source: Beijing Friendship Hospital
• Contact: Zhao Wang, MD
• Phone: 63138303
• Email: wangzhao[@]ccmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: October 1, 2025
• Est. primary completion date: July 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hemophagocytic Lymphohistiocytosis
• Lymphohistiocytosis, Hemophagocytic

Intervention

Drug:
• Venetoclax
Venetoclax 100mg qd d1,200mg qd d2,400mg qd d3-56
• 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
• Etoposide
Etoposide 75mg/m2 qw d1-56

Locations

Country	Name	City	State
China	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Friendship Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate	The percentage of cases with complete response (CR) and partial response (PR) after treatment in the total evaluable cases	1 year
Primary	Incidence and severity of adverse effects	The percentage of cases with adverse effects and its severity.	1 years
Secondary	Overall survival	OS is defined as the time from the initiaion of treatment to death from any cause or July 2025.	1 years