A Randomized Controlled Study of High-dose Cyclophosphamide Induction Therapy in Adult Patients With HLH

NCT05936086 | Recruiting DMC

• 1 other identifier: XYNK 04
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief 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. 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

Keywords

Hemophagocytic syndrome（HLH）

Outcome Measures

Primary Outcomes (2)

• complete response rate

  Efficacy evaluation measures included serum sCD25, ferritin, blood count, triglyceride, blood-phagocytosis, and consciousness level (CNS HLH) returning to normal range

  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%

  up to 30days

Secondary Outcomes (5)

• partial complete response rate

  up to 30days

• Single improvement degree among 8 indicators of diagnostic criteria

  up to 30days

• 30-day mortality rate

  up to 30days

• Antipyretic time

  up to 30days

• Invalid (NR) : Complete response and near Complete response are not satisfied, or one of the following conditions occurs

  up to 30days

Study Arms (2)

CTX(Cytoxan) group

EXPERIMENTAL

Drug: Cytoxan; Drug: Dexamethasone

Normal treatment group

ACTIVE COMPARATOR

Drug: Etoposide; Drug: Dexamethasone; Drug: Cyclosporine (CSA)

Interventions

Cytoxan DRUG

Cytoxan 40mg/kg iv qd x 2days (day 1 and 2);

CTX(Cytoxan) group

Etoposide DRUG

etoposide(VP16):150 mg/m2, twice a week, 1-2 weeks; 150mg/m2, once a week for the 3rd to 6th week.

Also known as: VP16

Normal treatment group

Dexamethasone DRUG

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.

CTX(Cytoxan) group; Normal treatment group

Cyclosporine (CSA) DRUG

Cyclosporine (CSA) 100mg Bid, week 1 to 6 (dosed according to 2004 version).

Normal treatment group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \&gt; 38.5 ℃, continuous \&gt; 7 d; ② Splenomegaly;
• Hemocytopenia (involving two or three peripheral blood lines) : hemoglobin \&lt; 90 g/L (\&lt; 4 weeks infant, hemoglobin \&lt; 100 g/L), platelet \&lt; 100×109/L, neutrophils \&lt; 1.0×109/L and not caused by reduced hematopoietic function of bone marrow; ④ High triglyceride (TG) sepsis and/or low fibrinogenemia: triglyceride \&gt; 3 mmol/L or 3 standard deviations above the same age, fibrinogen \&lt; 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• shifeng Lou: lead

Study Sites (1)

The Second affiliated Hosptial of Chongqing medical University

Chongqing, China

RECRUITING

MeSH Terms

Conditions

Lymphohistiocytosis, Hemophagocytic

Interventions

Cyclophosphamide; Etoposide; Dexamethasone; Cyclosporine

Condition Hierarchy (Ancestors)

Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Qing Wen, doctor

  Hematology Medical Center, the Second Affiliated Hospital of PLA Army Medical University

  STUDY DIRECTOR

• Huaer Shu, bachelor

  Chongqing Kaizhou District People's Hospital

  STUDY DIRECTOR

• Hongbin Zhang, doctor

  First Affiliated Hospital of Chongqing Medical University

  STUDY DIRECTOR

• Jinglong Lv, master

  Three Gorges Central Hospital Affiliated to Chongqing University

  STUDY DIRECTOR

• Zhangqin luo, bachelor

  Yongchuan Hospital affiliated to Chongqing Medical University

  STUDY DIRECTOR

• Liang Fang, master

  Chongqing Ninth People's Hospital

  STUDY DIRECTOR

• Yizhi Xu, doctor

  People's Hospital of Chongqing

  STUDY DIRECTOR

• Zailiang Yang, doctor

  Fuling Hospital affiliated to Chongqing University

  STUDY DIRECTOR

Central Study Contacts

shifeng Lou, master

CONTACT

13508331213; 13508331213@163.com

jianchuan Deng, master

CONTACT

15902305571; dengjccq@hospital.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: May 30, 2023
• First Posted: July 7, 2023
• Study Start: April 20, 2023
• Primary Completion: April 20, 2026
• Study Completion (Estimated): May 20, 2027
• Last Updated: August 30, 2023

Record last verified: 2023-08

Locations

CN (1)