Classic PNH and PNH with bone marrow failure
Conditions
Interventions
C5 monoclonal antibody group:C5 McAb 600mg was administered once a week for 4 weeks, and C5 McAb 900mg was administered once every two weeks from the fifth week, and then long-term administration.
Allogeneic hematopoietic stem cell transplantation group:Pretreatment scheme for full-sib compatibility:
Fludarabine (FLU) 30mg/m2/d × 6d (- 7 to -2D) + CY 50mg/kg/d × 2D (-4 to -3D) + ATG 2.5mg/kg/d
Allogeneic hematopoietic stem cell transplantation group:Alternative donor (unrelated donor, haplotype donor) conditioning regimen:
Busulfan (BU) 3.2 mg/kg/d (0.8 mg/kg, q6h) × 2D (-7 to -6d) + cyclop
Allogeneic hematopoietic stem cell transplantation group:Treatment regimen for GVHD: Grade II treatment, methylprednisolone 1 ~ 2mg/kg, divided into two doses, second-line drugs can be selected as app
Allogeneic hematopoietic stem cell transplantation group:Symptomatic and supportive treatment: Transplant-related complications such as infection, bleeding, hemorrhagic cystitis, epilepsy and mucositi
Sponsors
Hongci Hematology Branch of the First Affiliated Hospital of Soochow University
Eligibility
Sex/Gender
All
Age
14 Years to 50 Years
Inclusion criteria
Inclusion criteria: 1. Inclusion criteria of C5 monoclonal antibody group: 1) Adult male or female aged = 14 years, but not older than 14 years, sign the applicable informed consent form according to the patient's age and different research centers and national standards. 2) The patients enrolled in the study were all patients with definite diagnosis of PNH. According to the clinical classification criteria of PNH of the International Working Group, they met the criteria of classic PNH or PNH with bone marrow failure diseases such as MDS or AA. 3) Hemolysis (LDH = 1.5 ULN) was present at screening with any of the following symptoms: Hb < 7 G/dL or Hb < 10 G/dL in two independent tests, but with cardiac dysfunction; Thrombosis associated with PNH; Complications associated with hemolysis: renal insufficiency and pulmonary hypertension; Abdominal pain and/or dysphagia and/or erectile dysfunction; Pregnancy, especially in patients with a history of pregnancy complications. 4) Subjects must be vaccinated against Neisseria meningitidis to reduce the risk of meningococcal infection (Neisseria meningitidis).Subjects must be vaccinated at least 14 days prior to receiving the first C5 mAb if they have not been vaccinated, or if they are not within the protection period specified for the vaccine, and must receive appropriate antibiotic prophylaxis less than 14 days after vaccination until 14 days after vaccination. 5) Hematopoietic stem cell transplantation can not be performed due to the lack of suitable donors and the existence of transplantation contraindications.Or they can not bear the risks related to transplantation, refuse hematopoietic stem cell transplantation, and prefer drug treatment. 6) Willing to accept C5 monoclonal antibody therapy and having affordability; 7) The patient has the ability to understand and is willing to participate in the study, signs the informed consent form (ICF form), and is willing to comply with all study visits and procedures. Inclusion criteria for allogeneic hematopoietic stem cell transplantation 1) PNH with a definitive diagnosis of classic PNH or PNH with bone marrow failure diseases such as MDS or AA, according to the PNH International Working Group; 2) Age = 14 years old and less than 50 years old (the age of patients who are ineffective in other treatments and have good physical condition is relaxed to 60 years old). If the patient is not over 14 years old, the applicable informed consent shall be signed according to the age of the patient, different research centers and national standards. 3) Unwilling to accept C5 monoclonal antibody therapy and unable to afford long-term treatment costs; 4) No contraindication to hematopoietic stem cell transplantation; 5) Patients and their clients have the desire and request for hematopoietic stem cell transplantation; 6) relative donor or substitute donor of blood-providing hematopoietic stem cell 7) The therapeutic effect of C5 monoclonal antibody is not good. 8) The patient has the ability to understand and is willing to participate in the study, signs the informed consent form (ICF form), and is willing to comply with all study visits and procedures.
Exclusion criteria
Exclusion criteria: Exclusion criteria of C5 monoclonal antibody group: 1) History of malignant tumor before screening; 2) Uncontrolled active infection at the time of screening; 3) severe underlying diseases; 4) Severe organ dysfunction at screening, including a history of severe heart, lung, kidney, endocrine, and liver disease (e.g., active hepatitis); 5) The patient refused to be enrolled in the study; 6) Other conditions in which the subject is not considered suitable for participation in the study by the investigator. Exclusion criteria for allogeneic hematopoietic stem cell transplantation 1) Concomitant with other serious physical or mental illnesses that may affect the expression of the condition and the validity of the informed consent or lead to the patient's survival within 2 years; 2) Chronic infections (including bacterial, fungal or viral infections) that are difficult to control, such as dental caries, otitis media and sinusitis, should be carried out after effective control; 3) severe organ dysfunction; 4) decompensated hepatic insufficiency and active hepatitis; 5) History of severe autoimmune disease; 6) Other malignant tumors within 5 years; 7) History of severe allergy to biological products (including antibiotics); 8) Pregnant or lactating women.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Degree of hemolysis;Improvement of hemoglobin level;Overall survival and failure-free survival at 1 and 2 years after treatment;Overall survival, failure-free survival, relapse rate, and non-relapse-related mortality at 1 and 2 years after transplantation.; | — |
Secondary
| Measure | Time frame |
|---|---|
| Fatigue changes;Incidence of TE events;Improvement of renal function;Safety parameters include documented observation of adverse events (AEs);PHN clone;Hematopoietic reconstitution, engraftment, GVHD incidence, site and grade;Incidence of infection.; | — |
Countries
China
Contacts
Public ContactLimin Liu
Hongci Hematology Branch of the First Affiliated Hospital of Soochow University
Outcome results
None listed