Using Teniposide with Bu/Cy Conditioning for Treating HLH with Brain Involvement

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

This study is testing a new treatment using Teniposide with Bu/Cy before a stem cell transplant to see if it helps people with a serious condition called HLH that affects the brain.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 14 Years to 60 Years
• Sex: All
• Sponsor: Beijing Friendship Hospital (other)
• Locations: 1 site (Beijing)
• Trial ID: NCT06048107 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the efficacy and safety of a conditioning regimen that incorporates Teniposide and Bu/Cy prior to allogeneic hematopoietic stem cell transplantation (HSCT) for patients diagnosed with hemophagocytic lymphohistiocytosis (HLH) that involves the central nervous system (CNS). HLH is a severe inflammatory condition that can lead to rapid deterioration and high mortality, particularly when CNS symptoms are present. The study aims to address the lack of consensus on treatment for CNS-HLH by evaluating this specific conditioning regimen. Participants will be monitored for both the effectiveness of the treatment and any potential side effects.

Who should consider this trial

Good fit: Ideal candidates for this study are individuals diagnosed with HLH who exhibit CNS involvement and meet specific criteria for allogeneic HSCT.

Not a fit: Patients with HLH who do not have CNS involvement or those who do not meet the criteria for allogeneic HSCT may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve treatment outcomes for patients with CNS-HLH, potentially reducing mortality and improving quality of life.

How similar studies have performed: While there is limited consensus on the treatment of CNS-HLH, this study explores a novel approach that has not been widely tested in previous studies.

Eligibility criteria

Inclusion Criteria:

1. Diagnosed as HLH according to HLH-04 diagnostic criteria.
2. The indications for the presence of allogeneic hematopoietic stem cell transplantation (allo HSCT) include: I. Primary HLH; II. Refractory/recurrent HLH; III. Severe CNS-HLH.
3. According to the different causes of HLH, meeting the following conditions is defined as CNS-HLH.

   I. Definition of CNS-HLH in EBV-HLH: a significant increase of EBV-DNA copies/ml in peripheral blood or tissue or EBER(+) in tissue specimens or peripheral blood. Meanwhile cerebrospinal fluid EBV-DNA ≥5×10\^2 copies/ml.

   II.Definition of CNS-HLH in primary HLH: Nervous system symptom/sign or cerebrospinal fluid cell increase (\> 5 cells/μ L) and/or cerebrospinal fluid protein abnormality (\> 35mg/dL) and/or brain parenchyma or meningeal abnormality in cranial imaging during the onset or course of HLH.

   III. Definition of CNS-HLH of lymphoma-associated HLH: Cerebrospinal fluid flow cytology or brain histopathology confirmed that lymphoma involved CNS. Cerebrospinal fluid EBV-DNA ≥5×10\^2 copies/ml are also defined as CNS-HLH for EBV positive lymphoma-associated HLH.
4. Estimated survival time ≥ 1 month.
5. Age 14\~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 1×10\^2 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.

Where this trial is running

Beijing

• Zhao Wang — Beijing, China (RECRUITING)

Study contacts

• Principal investigator: Zhao Wang — Department of Hematology, Affiliated Beijing Friendship Hospital, Capital Medical University
• Study coordinator: Zhao Wang

Conditions: HLH