Hemophagocytic SyndromeNCT05936086
A Randomized Controlled Study of High-dose Cyclophosphamide Induction Therapy in Adult Patients With HLH
A study testing Cytoxan, Etoposide and Dexamethasone in people with Hemophagocytic Syndrome, run by shifeng Lou at 1 site in China.
Trial summary
Adult secondary HLH involves tumors, autoimmune diseases and other causes in addition to infection,Infectious factors, theoretically need different treatment methods for different etiology. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Hemophagocytic Syndrome
- What is being tested?
- Cytoxan, Etoposide and Dexamethasone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 1 siteChina
- Study dates
- 20 Apr 2023to 20 May 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age range from 18 to 65 years old (including the critical value), gender is not limited;
- According to the diagnostic criteria of HLH-2004, HLH can be diagnosed if any of the following two criteria are met:
- <!-- -->
- Molecular diagnosis is consistent with HLH: Currently known HLH related pathogenic genes exist, such as PRF1, UNC13D, STX11, STXBP2, Rab27a, LYST, SH2D1A, BIRC4, ITK, AP3β1, MAGT1, CD27 (cluster of differentiation antigen 27 )and other pathological mutations.
- Meet 5 or more of the following 8 indicators:
- Fever: body temperature \> 38.5 ℃, continuous \> 7 d; ② Splenomegaly;
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- Hemocytopenia (involving two or three peripheral blood lines) : hemoglobin \< 90 g/L (\< 4 weeks infant, hemoglobin \< 100 g/L), platelet \< 100×109/L, neutrophils \< 1.0×109/L and not caused by reduced hematopoietic function of bone marrow; ④ High triglyceride (TG) sepsis and/or low fibrinogenemia: triglyceride \> 3 mmol/L or 3 standard deviations above the same age, fibrinogen \< 1.5g /L or less than 3 standard deviations for the same age; (5) Hematophagy was found in bone marrow, spleen, liver or lymph nodes;
- The activity of NK cells is decreased or absent;
- ⑦ Serum ferritin increase: ferritin ≥500 μg/L; Elevated sCD25 (soluble interleukin-2 receptor). (3) Those who can understand the research content, agree to comply with the research plan, and voluntarily sign the informed consent.
Who cannot join
- HLH caused by treatable infectious causes (such as bacteria, fungi, viruses (except Epstein-Barr virus), protozoa, etc.);
- Have a history of allergy or contraindications to the drugs involved in the program;
- Organ damage caused by long-term chronic diseases;
- Extreme physical weakness, unstable vital signs and inability to tolerate large doses of cyclophosphamide;
- Severe and/or uncontrolled co-morbidivities (e.g., uncontrolled diabetes, pulmonary hypertension, etc.) that the investigator believes may pose an unacceptable safety risk or interfere with protocol compliance;
- Mental instability or history of severe mental illness
- Other factors determined by the researcher that subjects are not suitable to participate in this study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
The Second affiliated Hosptial of Chongqing medical University
Chongqing
Shifeng Lou, master
Jianchuan Deng
About this study
Adult secondary HLH involves tumors, autoimmune diseases and other causes in addition to infection,Infectious factors, theoretically need different treatment methods for different etiology. But adult HLH itself disease .The situation progresses ferociously, which can cause organ damage and blood coagulation disorder and endanger life quickly, with early mortality (30days).It can be more than 50%. On the other hand, although diagnostic techniques have improved significantly, identifying the cause is still costly Time, such as 1-2 weeks for the pathological diagnosis of lymphoma, leads to more patients losing further treatment due to early death.
The opportunity to heal. Therefore, it is important to explore effective induction therapy for adult HLH. In the majority ,Early (30-day) mortality was as high as 40% after cardiac induction using HLH2004 or CHOP(cyclophosphamide, hydroxydaunomycin, Oncovin, and prednisone) induction. HLH, on the other hand, usually requires prompt treatment before the cause is established. Due to a specific infection HLH can benefit from anti-infective therapy. Therefore, it is necessary to explore more effective induction therapy for adult non-infective HLH.It has very important clinical significance. Adult secondary HLH has the common features of a large number of T cell proliferation and activation and a significant reduction of NK(natural killer) cells, in which the central liNK(natural killer) is a large number of T cells proliferation and secomplete remission etion of cytokines, which can be used as induction therapy.Common target is also the pathological basis for designing unified induction scheme. Cyclophosphamide is a commonly used alkylated chemotherapy drug,It's also an important immunosuppressant. Based on the treatment of regenerative disorders anemia, allogeneic hematopoietic stem cell transplantation prevention.Experience with Plant versus Host disease (GVHD) has shown that the use of cyclophosphamide exceeds a total dose of 25mg/day,Two days can effectively kill CD8(cluster of differentiation 8 )+ or CD4(cluster of differentiation 4
)+T cells, and the maximum tolerated dose of this drug in humans exceeds 50mg/kg/day for two days. Aiming at the central liNK(natural killer) of adult HLH pathogenesis, The investigators designed for the first time to use a large dose of cyclophosphamide (25mg-50mg/kg/day 2days) to inhibit the activation of T cells, inhibit the production of cytokines and block the development mechanism of HLH. This study intends to conduct a randomized controlled study, with HLH2004 scheme as the control, and the observation is large efficacy and safety of dose cyclophosphamide in induction therapy of non-infective adult HLH in order to complete remission eate a new induction Treatment plan.
- Conditions
- Hemophagocytic Syndrome
- Being tested
- Cytoxan, Etoposide, Dexamethasone, Cyclosporine (CSA)
- Keywords
- Hemophagocytic syndrome（HLH）
- Medical subject headings
- Lymphohistiocytosis, Hemophagocytic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CytoxanDrug
Cytoxan 40mg/kg iv qd x 2days (day 1 and 2);
EtoposideDrug
Also called VP16
etoposide(VP16):150 mg/m2, twice a week, 1-2 weeks; 150mg/m2, once a week for the 3rd to 6th week.
DexamethasoneDrug
Dexamethasone: 10 mg/m2/day, week 1 to 2; 5 mg/m2/d for the 3rd to 4th week; 2.5 mg/m2/ day at week 5-6.
Cyclosporine (CSA)Drug
Cyclosporine (CSA) 100mg Bid, week 1 to 6 (dosed according to 2004 version).
| Study group | Role | What they receive |
|---|---|---|
| CTX(Cytoxan) group | Experimental | Not described Receives: Drug: Cytoxan; Drug: Dexamethasone |
| Normal treatment group | Active comparator | Not described Receives: Drug: Etoposide; Drug: Dexamethasone; Drug: Cyclosporine (CSA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
complete response rate
Efficacy evaluation measures included serum sCD25, ferritin, blood count, triglyceride, blood-phagocytosis, and consciousness level (CNS HLH) returning to normal range
Measured: up to 30days
Near complete response rate
Blood routine red blood cells, white blood cells, platelets returned to normal + other laboratory indicators improved by 50%
Measured: up to 30days
Secondary outcomes (5)
partial complete response rate
The antipyretic time, liver function, cytokine concentration, blood image recovery time and other indicators were better than the control group
Measured: up to 30days
Single improvement degree among 8 indicators of diagnostic criteria
Single improvement degree among 8 indicators of diagnostic criteria
Measured: up to 30days
30-day mortality rate
30-day mortality rate
Measured: up to 30days
Antipyretic time
Body temperature is back in the normal range
Measured: up to 30days
Invalid (NR) : Complete response and near Complete response are not satisfied, or one of the following conditions occurs
- The body temperature did not decrease for three consecutive days, and secondary bacterial or fungal infection could be excluded.
- Or continuous deterioration of liver function;
- Interleukin-2R and ferritin levels increased continuously.
- Coagulation dysfunction continues to worsen.
Measured: up to 30days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2023
- Study start20 Apr 2023
- Primary completion20 Apr 2026 (estimated)
- Study completion20 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hemophagocytic SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- shifeng Lou
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, shifeng Lou, The Second Affiliated Hospital of Chongqing Medical University
- Investigators
- Qing Wen, doctor, Study director, Hematology Medical Center, the Second Affiliated Hospital of PLA Army Medical UniversityHuaer Shu, bachelor, Study director, Chongqing Kaizhou District People's HospitalHongbin Zhang, doctor, Study director, First Affiliated Hospital of Chongqing Medical UniversityJinglong Lv, master, Study director, Three Gorges Central Hospital Affiliated to Chongqing UniversityZhangqin luo, bachelor, Study director, Yongchuan Hospital affiliated to Chongqing Medical UniversityLiang Fang, master, Study director, Chongqing Ninth People's HospitalYizhi Xu, doctor, Study director, People's Hospital of ChongqingZailiang Yang, doctor, Study director, Fuling Hospital affiliated to Chongqing University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05936086
- Sponsor's protocol ID
- XYNK 04
- Status last verified
- Aug 2023
- First submitted
- 30 May 2023
- Last updated
- 30 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Study of High-dose Cyclophosphamide Induction Therapy in Adult Patients With HLH
- ClinicalTrials.gov ID
- NCT05936086
- Acronym / sponsor ID
- XYNK 04
- Conditions
- Hemophagocytic Syndrome
- Keywords
- Hemophagocytic syndrome（HLH）
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- shifeng LouUniversity, hospital or other
- Study start
- 20 Apr 2023 (actual)
- Primary completion
- 20 Apr 2026 (estimated)
- Study completion
- 20 May 2027 (estimated)
- First posted
- 7 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Adult secondary HLH involves tumors, autoimmune diseases and other causes in addition to infection,Infectious factors, theoretically need different treatment methods for different etiology. But adult HLH itself disease .The situation progresses ferociously, which can cause organ damage and blood coagulation disorder and endanger life quickly, with early mortality (30days).It can be more than 50%. On the other hand, although diagnostic techniques have improved significantly, identifying the cause is still costly Time, such as 1-2 weeks for the pathological diagnosis of lymphoma, leads to more patients losing further treatment due to early death.
The opportunity to heal. Therefore, it is important to explore effective induction therapy for adult HLH. In the majority ,Early (30-day) mortality was as high as 40% after cardiac induction using HLH2004 or CHOP(cyclophosphamide, hydroxydaunomycin, Oncovin, and prednisone) induction. HLH, on the other hand, usually requires prompt treatment before the cause is established. Due to a specific infection HLH can benefit from anti-infective therapy. Therefore, it is necessary to explore more effective induction therapy for adult non-infective HLH.It has very important clinical significance. Adult secondary HLH has the common features of a large number of T cell proliferation and activation and a significant reduction of NK(natural killer) cells, in which the central liNK(natural killer) is a large number of T cells proliferation and secomplete remission etion of cytokines, which can be used as induction therapy.Common target is also the pathological basis for designing unified induction scheme. Cyclophosphamide is a commonly used alkylated chemotherapy drug,It's also an important immunosuppressant. Based on the treatment of regenerative disorders anemia, allogeneic hematopoietic stem cell transplantation prevention.Experience with Plant versus Host disease (GVHD) has shown that the use of cyclophosphamide exceeds a total dose of 25mg/day,Two days can effectively kill CD8(cluster of differentiation 8 )+ or CD4(cluster of differentiation 4
)+T cells, and the maximum tolerated dose of this drug in humans exceeds 50mg/kg/day for two days. Aiming at the central liNK(natural killer) of adult HLH pathogenesis, The investigators designed for the first time to use a large dose of cyclophosphamide (25mg-50mg/kg/day 2days) to inhibit the activation of T cells, inhibit the production of cytokines and block the development mechanism of HLH. This study intends to conduct a randomized controlled study, with HLH2004 scheme as the control, and the observation is large efficacy and safety of dose cyclophosphamide in induction therapy of non-infective adult HLH in order to complete remission eate a new induction Treatment plan.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CTX(Cytoxan) group | Experimental | Drug: Cytoxan, Drug: Dexamethasone |
| Normal treatment group | Active comparator | Drug: Etoposide, Drug: Dexamethasone, Drug: Cyclosporine (CSA) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age range from 18 to 65 years old (including the critical value), gender is not limited;
- According to the diagnostic criteria of HLH-2004, HLH can be diagnosed if any of the following two criteria are met:
- <!-- -->
- Molecular diagnosis is consistent with HLH: Currently known HLH related pathogenic genes exist, such as PRF1, UNC13D, STX11, STXBP2, Rab27a, LYST, SH2D1A, BIRC4, ITK, AP3β1, MAGT1, CD27 (cluster of differentiation antigen 27 )and other pathological mutations.
- Meet 5 or more of the following 8 indicators:
Key exclusion criteria (7 listed)
- HLH caused by treatable infectious causes (such as bacteria, fungi, viruses (except Epstein-Barr virus), protozoa, etc.);
- Have a history of allergy or contraindications to the drugs involved in the program;
- Organ damage caused by long-term chronic diseases;
- Extreme physical weakness, unstable vital signs and inability to tolerate large doses of cyclophosphamide;
- Severe and/or uncontrolled co-morbidivities (e.g., uncontrolled diabetes, pulmonary hypertension, etc.) that the investigator believes may pose an unacceptable safety risk or interfere with protocol compliance;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CytoxanCytoxan 40mg/kg iv qd x 2days (day 1 and 2); | Drug | CTX(Cytoxan) group |
| EtoposideAlso: VP16etoposide(VP16):150 mg/m2, twice a week, 1-2 weeks; 150mg/m2, once a week for the 3rd to 6th week. | Drug | Normal treatment group |
| DexamethasoneDexamethasone: 10 mg/m2/day, week 1 to 2; 5 mg/m2/d for the 3rd to 4th week; 2.5 mg/m2/ day at week 5-6. | Drug | CTX(Cytoxan) group, Normal treatment group |
| Cyclosporine (CSA)Cyclosporine (CSA) 100mg Bid, week 1 to 6 (dosed according to 2004 version). | Drug | Normal treatment group |
Primary outcome
complete response rate
Time frame: up to 30days
Efficacy evaluation measures included serum sCD25, ferritin, blood count, triglyceride, blood-phagocytosis, and consciousness level (CNS HLH) returning to normal range
Near complete response rate
Time frame: up to 30days
Blood routine red blood cells, white blood cells, platelets returned to normal + other laboratory indicators improved by 50%
5 secondary outcomes
partial complete response rate
Time frame: up to 30days
Single improvement degree among 8 indicators of diagnostic criteria
Time frame: up to 30days
30-day mortality rate
Time frame: up to 30days
Antipyretic time
Time frame: up to 30days
Invalid (NR) : Complete response and near Complete response are not satisfied, or one of the following conditions occurs
Time frame: up to 30days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2023.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Qing Wen, doctor study director
Hematology Medical Center, the Second Affiliated Hospital of PLA Army Medical University
Huaer Shu, bachelor study director
Chongqing Kaizhou District People's Hospital
Hongbin Zhang, doctor study director
First Affiliated Hospital of Chongqing Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cytoxan, Etoposide and Dexamethasone in people with Hemophagocytic Syndrome, run by shifeng Lou at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact shifeng Lou, master (13508331213, 13508331213@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
complete response rate (time frame: up to 30days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Aug 2023; AzTrials last refreshed its copy on 26 Oct 2026.