patients with difficulty in high-dose post-transplant cyclophosphamide (PT-CY)
Conditions
Interventions
Following pre-transplant treatment according to the treatment regimen according to the patient's condition, rituximab (genetical recombination) will be administered to prevent the development of PTLD,
Sponsors
Iguchi Akihiro
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients who meet all of the following criteria are included in this study. (1) Patients who meet any of the following criteria and are judged to be difficult to perform PT-CY transplantation. (a) Patients with DNA repair disorders such as Fanconi anemia (FA) (b) Patients who require hematopoietic cell transplantation in early infancy such as severe combined immunodeficiency (SCID) (c) Patients who have reached the maximum dose of anthracycline (500 mg/m2 doxorubicin equivalent) or cannot receive large doses of CY due to CY allergy (2) Patients who require hematopoietic cell transplantation but do not have an HLA 7/8(A, B, C, DRB1) -matched or 8/8 -matched donor at enrollment. (3) Patients who have at least 2 donors who meet one of the following criteria at enrollment (a) HLA4/8(A, B, C, DRB1) -matched related donors (b) HLA5/8(A, B, C, DRB1) -matched related donors (c) HLA6/8(A, B, C, DRB1) -matched related donors (4) Patients aged over 3 months and < 18 years at enrollment (5) Patients with an ECOG performance status (PS) score of 0~2 at enrollment (6) Patients with adequate organ function that meets the following criteria at enrollment. Laboratory values are the most recent values within 14 days prior to enrollment. (a) Serum direct bilirubin level: 1.5 mg/dL or less (b) Serum creatinine level: < 5 years, 0.8 mg/dL or less over 5 years and < 10 years, 1.2 mg/dL or less over 10 years, 1.5 mg/dL or less (c) Cardiac function: Left ventricular ejection fraction (ejection fraction 45% or over) and QTc <0.45 seconds (7) Patients who can be hospitalized from the day of pretreatment until 3 months after transplantation (8) Patients for whom written consent to participate in this study has been obtained from the surrogate (However, in the case of patients aged 16 to < 18 years, patients who have also obtained written consent to participate in the study)
Exclusion criteria
Exclusion criteria: Patients who meet any of the following criteria at enrollment shall be excluded. (1) Patients who have received hematopoietic cell transplantation other than in this study (2) Patients who are sensitive or allergic to mouse-derived components, or patients with a history of hypersensitivity to rituximab (genetical recombination) components (3) Patients whose prospective donor cannot use G-CSF due to allergy or other reasons (4) Patients who fall under any of the following infections (a) through (e) (a) Patients with serious infections (Pneumonia, pyelonephritis, etc.) requiring hospitalization (b) Patients with uncontrolled opportunistic infections (Cytomegalovirus infection, systemic fungal infection, Pneumocystis infection, non-tuberculous mycobacterial infection, etc.) (c) Patients with active tuberculosis (d) Patients with a history of or suspected of having tuberculosis infection (e) Patients with confirmed HIV infection (5) Patients who tested positive for HBsAg, antibody to HBs, antibody to HBc, or antibody to HCV at enrollment. However, patients who meet the following criteria will be eligible for enrollment. (a) Patients who are positive for antibody to HBs and who have received hepatitis B vaccine have a negative HBV-DNA assay (less than detection sensitivity). (A history of hepatitis B vaccination should be confirmed at the time of screening, and if anti-HBs positivity is possible, a quantitative HBV-DNA test should also be performed.) (b) Patients who are positive for antibody to HCV have a negative HCV-RNA assay (less than detection sensitivity). (6) Patients who have received live vaccine within 4 weeks prior to enrollment (7) Patients with uncontrolled hypertension despite antihypertensive treatment at enrollment (8) Patients with severe mental disorders (9) Patients who do not provide consent to use contraception during study participation and for 12 months after administration of rituximab (genetical recombination) (10) Women who are pregnant, lactating, or possibly pregnant (serum HCG or urine HCG must be confirmed at screening) (11) Patients who received anti-CD 20 antibody preparations including rituximab (genetical recombination) within 6 months prior to enrollment outside of this study (12) Patients who have received an investigational product within 6 months prior to enrollment outside of this study or who plan to participate in another study during study participation (13) Patients who are deemed ineligible by the investigator (subinvestigator)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Event-free survival up to 100 days after transplantation (Events: primary engraftment failure, any death, grade 3 or over acute GVHD, development of PTLD) | — |
Secondary
| Measure | Time frame |
|---|---|
| (1) Efficacy endpoints 1) Overall survival 2) Death by 100 days after transplantation 3) Grade 3 or over acute GVHD onset by 100 days after transplantation 4) PTLD onset by 100 days after transplantation 5) Primary engraftment failure by 100 days after transplantation 6) Relapse-free survival 7) Acute GVHD-free (grade 2 or over) survival 8) Chronic GVHD-free survival 9) PTLD-free survival 10) Donor-derived platelet count 20,000/microL or over reached 11) Development of malignant tumors after transplantation 12) Development of secondary engraftment failure 13) Efficiency of removal of alpha beta T cells and CD19 + cells 14) Recovery rate of CD34 + cells 15) Percentage of viable cells 16) Number of cells infused (Total cell count, CD34 + cell count, alpha beta T cell count, gamma delta T cell count, CD19 + cell count, NK cell count) (2) Safety endpoint 1) Adverse events and adverse drug reactions 2) Non-hematological Grade 4 or over adverse events 3) Infusion reaction associated with rituximab 4) Occurrence of study device failure 5) Laboratory tests and vital signs 6) Transplantation treatment-related death by 100 days 7) Occurrence of transplant treatment-related complications by 1 year 8) Occurrence of infection by 100 days | — |
Contacts
Public ContactCoordinating Office Clinical Traial
National Center for Child Health and Development
Outcome results
None listed