Thiotepa Incorporating TBI/Cy Conditioning Regimen for EBV-HLH With Central Nervous System Involvement

HLH Clinical Trial

Official title:

Thiotepa Incorporating TBI/Cy Conditioning Regimen Followed by HSCT for EBV-HLH With Central Nervous System Involvement: a Prospective Single-arm Clinical Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05854225
• Other study ID #: 2021-P2-250-01
• Status: Recruiting
• Phase: N/A
• Start date: January 1, 2022
• Est. completion date: January 2025

Study information

• Verified date: May 2023
• Source: Beijing Friendship Hospital
• Contact: wang zhao, MD
• Phone: 63138303
• Email: wangzhao[@]ccmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

EBV-HLH is the most common in virus-associated hemophagocytic syndrome (VAHS). There are no uniform clinical criteria for the diagnosis of CNS-HLH. And there is still a lack of international consensus on the treatment for CNS-HLH. Following allogeneic HSCT after HLH induction therapy is recommended for CNS-HLH. One of the major factors influencing the transplantation effect is conditioning. Therefore, we conduct a prospective clinical study to explore the efficacy and safety of thiotepa incorporating TBI/Cy conditioning regimen followed by allogeneic hematopoietic stem cell transplantation for EBV-HLH with central nervous system involvement.

Description:

HLH is an immune disorder characterized by a potentially fatal cytokine storm induced by uncontrolled T lymphocyte and macrophage activation. EBV-HLH is the most common in virus-associated hemophagocytic syndrome (VAHS). There are no uniform clinical criteria for the diagnosis of CNS-HLH. And there is still a lack of international consensus on the treatment for CNS-HLH. CNS involvement is one of the factors in the poor prognosis for HLH. Following allogeneic HSCT after HLH induction therapy is recommended for CNS-HLH. One of the major factors influencing the transplantation effect is conditioning. Therefore, we conduct a prospective clinical study to explore the efficacy and safety of thiotepa incorporating TBI/Cy conditioning regimen followed by allogeneic hematopoietic stem cell transplantation for EBV-HLH with central nervous system involvement.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: January 2025
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. Diagnosed as HLH according to HLH-04 diagnostic criteria.

2. a significant increase of EBV-DNA copies/ml in peripheral blood or tissue or EBER(+) in tissue specimens or peripheral blood.

3. Cerebrospinal fluid EBV-DNA =5×10^2 copies/ml.

4. Estimated survival time = 1 month.

5. Age 18~60, gender is not limited.

6. Total bilirubin = 2 times the upper limit of normal; serum creatinine = normal value before study entry.

7. Serum HIV antigen or antibody negative.

8. HCV antibody negative.

9. HBsAg negative, HBcAb negative. If any of the above is positive, then HBV-DNA titer in peripheral blood is required less than 1×102 copies/ml before enrollment.

10. Cardiac ultrasound LVEF=50%.

11. Women in the child-bearing period must not be pregnant as determined by a pregnancy test and must be willing to use effective contraception during the trial and for = 12 months after the last dose. Pregnant and lactating women cannot participate. All male subjects accept contraception during the trial and for =6 months after the last dose.

12. Signed informed consent.

Exclusion Criteria:

1. Heart function above grade II (NYHA).

2. Active bleeding of the internal organs(digestive tract, lung, brain, etc.).

3. Uncontrolled infection (pulmonary infection, intestinal infection, etc.).

4. Severe mental illness.

5. Patients are unable to comply during the trial and/or follow-up phase.

6. Participate in other clinical research at the same time.

Related Conditions & MeSH terms

• HLH

Intervention

Drug:
• Thiotepa
Thiotepa is an alkylating agent that is routinely used in solid tumors, but it is able to cross the blood-brain barrier into the center.

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	The clinical remission rate	The number of cases with complete response (CR) and partial response (PR) after transplantation as a percentage of the total cases.	24 weeks