Clinical trial NCT05854225: Thiotepa Incorporating TBI/Cy Conditioning Regimen for EBV-HLH With Central Nervous System Involvement
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: HLH
Lead sponsor: Beijing Friendship Hospital
Sponsor class: OTHER
First posted: 2023-05-11
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: The clinical remission rate
timeFrame: 24 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
Study officials:
affiliation: Beijing Friendship Hospital
name: wang zhao, MD
role: PRINCIPAL_INVESTIGATOR
References: