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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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HLH

Intervention / Treatment
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* Drug: Thiotepa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed as HLH according to HLH-04 diagnostic criteria. a significant increase of EBV-DNA copies/ml in peripheral blood or tissue or EBER(+) in tissue specimens or peripheral blood. Cerebrospinal fluid EBV-DNA ≥5×10^2 copies/ml. Estimated survival time ≥ 1 month. Age 18 60， gender is not limited. Total bilirubin ≤ 2 times the upper limit of normal; serum creatinine ≤ normal value before study entry. Serum HIV antigen or antibody negative. HCV antibody negative. 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. Cardiac ultrasound LVEF≥50%. 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. Signed informed consent. Exclusion Criteria: Heart function above grade II (NYHA). Active bleeding of the internal organs(digestive tract, lung, brain, etc.). Uncontrolled infection (pulmonary infection, intestinal infection, etc.). Severe mental illness. Patients are unable to comply during the trial and/or follow-up phase. Participate in other clinical research at the same time.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: single-arm<br>a prospective single-arm clinical study | Drug: Thiotepa<br>* 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.<br>* Other names: TT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |