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

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

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.

Study Overview

• Status: Recruiting
• Conditions: HLH
• Intervention / Treatment: Drug: Thiotepa

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.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: wang zhao, 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: zhaowww263@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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.

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
Other: single-arm; a prospective single-arm clinical study	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.; Other Names: TT

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Beijing Friendship Hospital
• Investigators: Principal Investigator: wang zhao, MD, Beijing Friendship Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Anticipated): June 1, 2024
• Study Completion (Anticipated): January 1, 2025

Study Registration Dates

• First Submitted: April 20, 2023
• First Submitted That Met QC Criteria: May 10, 2023
• First Posted (Estimate): May 11, 2023

Study Record Updates

• Last Update Posted (Estimate): May 11, 2023
• Last Update Submitted That Met QC Criteria: May 10, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Thiotepa
• Other Study ID Numbers: 2021-P2-250-01

Drug and device information, study documents

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