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

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

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

Study Overview

• Status: Recruiting
• Conditions: Hemophagocytic Lymphohistiocytosis
• Intervention / Treatment: Drug: Venetoclax; Drug: Dexamethasone; Drug: Etoposide

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 Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Zhao Wang, MD; Phone Number: 63138303; Email: wangzhao@ccmu.edu.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100050
      • Recruiting
      • Beijing Friendship Hospital, Capital Medical University
      • Contact: Zhao Wang, MD; Phone Number: 63138303; Email: wangzhao@ccmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	OS is defined as the time from the initiaion of treatment to death from any cause or July 2025.	1 years

Collaborators and Investigators

• Sponsor: Beijing Friendship Hospital
• Investigators: Principal Investigator: Zhao Wang, MD, Beijing Friendship Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2022
• Primary Completion (Anticipated): July 1, 2025
• Study Completion (Anticipated): October 1, 2025

Study Registration Dates

• First Submitted: September 15, 2022
• First Submitted That Met QC Criteria: September 15, 2022
• First Posted (Actual): September 19, 2022

Study Record Updates

• Last Update Posted (Actual): September 19, 2022
• Last Update Submitted That Met QC Criteria: September 15, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Venetoclax; Hemophagocytic Lymphohistiocytosis
• Additional Relevant MeSH Terms: Lymphatic Diseases; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphohistiocytosis, Hemophagocytic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Dexamethasone; Etoposide; Venetoclax
• Other Study ID Numbers: BFH20220425006/BFHHZS20220026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No