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IRCT20200413047063N6 IRCT 2025-05-24 Omid cell and tissue tech Exosome therapy in steroid-resistant acute Graft Versus Host Disease (GVHD) patients Evaluating the Safety of Placenta Mesenchymal Stem Cells-derived Exosomes (HP-MSCs-derived Exosomes) in the Treatment of Steroid-Resistant Acute GVHD after Allogeneic Hematopoietic Stem Cell Transplantation: Clinical Trial Phase I 2024-12-30 anticipated 12 Recruiting https://irct.ir/trial/78690 interventional Randomization: Not randomized, Blinding: Not blinded, Placebo: Not used, Assignment: Single, Purpose: Treatment. 1 Acute steroid-resistant graft-versus-host disease. Intervention group: Patients diagnosed with grade II to IV acute Graft Versus Host Disease (aGVHD), whose response to treatment with corticosteroids equal or more than 2 milligram per kilogram (mg/kg) is poor and symptoms progress in three days or stable disease for five days, after informed written consent will be included in the study. The diagnosis of Steroid resistant acute graft versus host disease (SR-aGVHD) is based on the diagnosis, grading and staging of aGVHD according to clinical observations and criteria suggested by the International Blood and Bone Marrow Transplant Research Center. Exosome derived from placenta mesenchymal stem cells from donors after obtaining a written consent from the donor, several tests are performed for the absence of contamination. Then the mesenchymal cells are separated under sterile conditions (Good Manufacturing Practices (GMP) grade) and after the characteristic finding in sterile vials will be transferred to the hospital and will be used as an intravenous injection for patients. In each exosome injection, 1 unit of human placenta -derived mesenchymal stem cell exosome (HP-MSC-EXO) is approximately equivalent to the number of exosome particles, which is prepared from 101 x 108 cells, which is administered in the same amount of HP-MSC-EXO in the recipient group weighting 50 to 80 kilogram. The dose of exosome based on studies is 50 microgram per milliliter (μg/mL) and is equivalent to 250-300 milligram of exosome in each vial. Agonists of H1 and H2 receptors are prescribed to prevent allergic reactions before injection and patients are constantly monitored for 2 hours. Exosome injection is done in the form of three doses on the first day after an interval of 8 hours (TDS) and maintenance injection is done daily for 5 days, which dose will be done based on a pilot study conducted in Taleghani Hospital. In this group, the prescription of other treatment protocols, especially Infliximab, is not allowed under any circumstances, and if prescribed, the patient will be excluded from the study. Until the complete failure of the treatment, the prescription of other treatment protocols, especially Infliximab, is prohibited.***The therapeutic intervention method and scientific history and the theoretical basis of the method and its research history as well as the possibility of side effects are accurately and transparently informed to the patient or his companions (often the companions of the patient due to the bad condition of the patients) and the relevant therapeutic intervention it is done with their consent. The information of the patients is collected every day by the researcher who collects the information by filling out a special form. The method of collecting information is based on talking to the patient in his clinic and examining the file to check the symptom registration forms and the results of clinical tests.***Patients assessment in terms of recurrence of aGVHD and infection, complications of cell therapy (safety), recurrence of the disease at intervals of 7+, 21+ and 28+ days after the first exosome injection. Patients are evaluated based on Glusburg criteria (based on GvHD grade) at intervals of +14, +21 and +28 days after the first injection. All patients who receive exosome should wash the route of exosome injection with distilled water immediately before and after injection. Vital signs of patients are constantly checked; Especially, the symptoms one hour after drug injection and as an investigation of the possible effects of the drug are recorded in the results. Any unwanted complication or unusual event is recorded so that it can be recorded in the results if a possible complication occurs. If the condition of the recipient of exosome worsens, the patient will be excluded from the study and the patient will be a candidate for drug or cell therapy.. Undecided - It is not yet known if there will be a plan to make this available Justification or reason for indecision in sharing IPD is There is no further information
public Masoud Soleimani
West Qabadian St.
Tehran Iran (Islamic Republic of) 1968917313 +98 912 287 5993 soleim_m@modares.ac.ir Omid cell and tissue tech scientific Masoud Soleimani
West Qabadian St.
Tehran Iran (Islamic Republic of) 1968917313 +98 912 287 5993 soleim_m@modares.ac.ir Omid cell and tissue tech Iran (Islamic Republic of) Patients diagnosed with grade II to IV acute Graft versus host disease (GVHD) whose response to treatment with corticosteroids equal to or more than 2 milligrams per kilogram is poor, and the disease symptoms progress in three days or have stable disease for five days Patients over 18 years old Patients of both sexes Signed written informed consent 18 years 65 years Both Patients who have recurrence of the main disease (cancer) Patients who, in the differential diagnosis of clinical symptoms, have causes other than acute graft versus host disease (aGVHD) indicating the patient, such as patients with symptoms Sinusoidal Obstruction Syndrome (SOS), maculopapular skin rashes with drug or viral causes or Engraftment Syndrome, viral diarrheas, etc Patients who have been prescribed Infliximab The presence of an active uncontrolled infection, including a significant bacterial, fungal, viral or parasitic infection that requires treatment Presence of recurrent primary malignancy, or those treated for recurrence after Hematopoietic Cell Transplantation (HCT), or those who may require rapid removal of immunosuppression as pre-emergency treatment of primary recurrence Have unresolved venous occlusion disease Patients who have any underlying or current medical or psychiatric problems that the researcher thinks may be a disorder (uncontrolled infection, cardiovascular failure, and pulmonary pressure) Patients who have any allergy to blood products D89.810 Acute graft-versus-host disease Treatment - Other Intervention group: Patients diagnosed with grade II to IV acute Graft Versus Host Disease (aGVHD), whose response to treatment with corticosteroids equal or more than 2 milligram per kilogram (mg/kg) is poor and symptoms progress in three days or stable disease for five days, after informed written consent will be included in the study. The diagnosis of Steroid resistant acute graft versus host disease (SR-aGVHD) is based on the diagnosis, grading and staging of aGVHD according to clinical observations and criteria suggested by the International Blood and Bone Marrow Transplant Research Center. Exosome derived from placenta mesenchymal stem cells from donors after obtaining a written consent from the donor, several tests are performed for the absence of contamination. Then the mesenchymal cells are separated under sterile conditions (Good Manufacturing Practices (GMP) grade) and after the characteristic finding in sterile vials will be transferred to the hospital and will be used as an intravenous injection for patients. In each exosome injection, 1 unit of human placenta -derived mesenchymal stem cell exosome (HP-MSC-EXO) is approximately equivalent to the number of exosome particles, which is prepared from 101 x 108 cells, which is administered in the same amount of HP-MSC-EXO in the recipient group weighting 50 to 80 kilogram. The dose of exosome based on studies is 50 microgram per milliliter (μg/mL) and is equivalent to 250-300 milligram of exosome in each vial. Agonists of H1 and H2 receptors are prescribed to prevent allergic reactions before injection and patients are constantly monitored for 2 hours. Exosome injection is done in the form of three doses on the first day after an interval of 8 hours (TDS) and maintenance injection is done daily for 5 days, which dose will be done based on a pilot study conducted in Taleghani Hospital. In this group, the prescription of other treatment protocols, especially Infliximab, is not allowed under any circumstances, and if prescribed, the patient will be excluded from the study. Until the complete failure of the treatment, the prescription of other treatment protocols, especially Infliximab, is prohibited.***The therapeutic intervention method and scientific history and the theoretical basis of the method and its research history as well as the possibility of side effects are accurately and transparently informed to the patient or his companions (often the companions of the patient due to the bad condition of the patients) and the relevant therapeutic intervention it is done with their consent. The information of the patients is collected every day by the researcher who collects the information by filling out a special form. The method of collecting information is based on talking to the patient in his clinic and examining the file to check the symptom registration forms and the results of clinical tests.***Patients assessment in terms of recurrence of aGVHD and infection, complications of cell therapy (safety), recurrence of the disease at intervals of 7+, 21+ and 28+ days after the first exosome injection. Patients are evaluated based on Glusburg criteria (based on GvHD grade) at intervals of +14, +21 and +28 days after the first injection. All patients who receive exosome should wash the route of exosome injection with distilled water immediately before and after injection. Vital signs of patients are constantly checked; Especially, the symptoms one hour after drug injection and as an investigation of the possible effects of the drug are recorded in the results. Any unwanted complication or unusual event is recorded so that it can be recorded in the results if a possible complication occurs. If the condition of the recipient of exosome worsens, the patient will be excluded from the study and the patient will be a candidate for drug or cell therapy. Recurrence of acute Graft Versus Host Disease (aGVHD) and infection. Timepoint: 7, 21 and 28 days after injection. Method of measurement: History, Physical exam, and lab test. Overall Remission Rate (ORR). Timepoint: 7, 21 and 28 days after injection. Method of measurement: Assessed using the Glusburg (based on GvHD grade). Progression-free survival (PFS). Timepoint: 48 weeks after exosome infusion. Method of measurement: Assessed using the Graft-versus-Host Disease Working Committee. Duration of Response (DOR). Timepoint: 48 weeks after exosome infusion. Method of measurement: Assessed using the Graft-versus-Host Disease Working Committee. Shahid Beheshti University of Medical Sciences Omid cell and tissue tech Shahid Beheshti University of Medical Sciences Approved 2024-05-12 Ethics Committee of Shahid Beheshti University of Medical Sciences Tehran Province, Tajrish، Velenjak، 7th Floor, Bldg No.2 SBUMS, Arabi Ave Tehran Tehran Iran (Islamic Republic of)