Protocol summary
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Study aim
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Evaluation of the safety and effectiveness of IV injection of placenta-derived mesenchymal stem cells and exosomes of placenta-derived mesenchymal stem cells in steroid-resistant acute GvHD patients; Phase I and II clinical trials
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Design
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A phase 1-2 clinical trial study has a control group with 60 patients, with parallel groups and double-blind and randomized. Randomization is simple.
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Settings and conduct
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This double-blind clinical trial is conducted on 60 patients with aGvHD in Shariati Hospital. Patients in three groups of cells, exosome and ruxolitinib are treated and followed up according to the protocol.
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Participants/Inclusion and exclusion criteria
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Inclusion criteria: patients aged 12 to 65 years - patients with acute aGvHD grade II-IV according to MAGIC criteria and steroid resistant according to EBMT-NIH-CIBMTR, patients who underwent allogeneic HSCT with the following conditions: related donor HLA (MRD), HLA unrelated donor (MUD), unrelated cord blood (UCB), haploidal donor - Exclusion criteria: positive serology for hepatitis B, C and HIV or fungal infection - uncontrolled diseases including persistent or active infection, symptomatic CHF, unstable angina, cardiac arrhythmia, transplant recipient for solid tumor - diagnosis of sinus occlusion syndrome (SOS) or veno-occlusive disease - pregnancy or lactation
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Intervention groups
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A: IV injection of a solution containing mesenchymal stem cells (MSCs) obtained from the human placenta from Viracellule Company, 1 million cells / kg of body weight, 4 times at intervals of 3 days. B: IV injection of a solution containing 1.2 x 10^12 exosome of MSCs obtained from the human placenta from Viracellule Company, 4 times with an interval of every 3 days. C: Ruxolitinib drug, Nano Alvand Company, 5 mg twice a day, orally, from day 0 to day 28 after injection.
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Main outcome variables
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Adverse events, complete response rate, overall survival rate
General information
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Reason for update
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Modifying the sample size based on the approval of the Research Council of the Research Center of Hematology, Oncology and cell Therapy - Tehran University of Medical Sciences
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Acronym
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IRCT registration information
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IRCT registration number:
IRCT20140818018842N40
Registration date:
2024-06-09, 1403/03/20
Registration timing:
prospective
Last update:
2024-07-03, 1403/04/13
Update count:
1
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Registration date
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2024-06-09, 1403/03/20
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Registrant information
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Recruitment status
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recruiting
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Funding source
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Expected recruitment start date
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2024-06-21, 1403/04/01
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Expected recruitment end date
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2025-12-22, 1404/10/01
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Actual recruitment start date
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empty
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Actual recruitment end date
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empty
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Trial completion date
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empty
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Scientific title
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Evaluaing the safety and effectiveness of intravenous infusion of placenta-derived mesenchymal stem cells and placenta-derived mesenchymal stem cell exosomes in steroid-resistant acute GvHD patients; Phase I and II clinical trial
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Public title
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Placenta-derived mesenchymal stem cells and placenta-derived mesenchymal stem cells exosomes in the treatment of acute GvHD
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Purpose
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Treatment
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Inclusion/Exclusion criteria
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Inclusion criteria:
Acute aGvHD grade II-IV according to MAGIC criteria and steroid resistant according to EBMT-NIH-CIBMTR
A patient who underwent allogeneic HSCT with the following conditions: HLA-matched donor (MRD), HLA-mismatched donor (MUD), unrelated cord blood (UCB), haploidal donor
Exclusion criteria:
Positive serology for hepatitis B, hepatitis C and AIDS virus or fungal infection
Patients with penicillin and/or gentamicin allergy or known allergy to cow or pork products
Participants with uncontrolled diseases including persistent or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness or specific social situations that limit compliance with study requirements
Any condition that, in the investigator's judgment, interferes with full participation in the study, including the administration of study medication or participation in required study visits, or poses a significant risk to the participant, or interferes with the interpretation of study data
Transplant recipient for solid tumor
Diagnosis of Sinus Obstructive Syndrome (SOS) or Venous Obstructive Disease, at any time of study with appropriate tests
Pregnancy and breastfeeding
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Age
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From 12 years old to 65 years old
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Gender
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Both
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Phase
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1-2
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Groups that have been masked
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- Participant
- Care provider
- Investigator
- Outcome assessor
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Sample size
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Target sample size:
60
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Randomization (investigator's opinion)
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Randomized
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Randomization description
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In this study,In order to reduce bias, randomization is done by online randomization method by a statistician. the randomization process was conducted using the Clinical Trial Randomization Tool provided by the National Cancer Institute (NCI) https://ctrandomization.cancer.gov/ to assign 60 participants to 3 groups: Group A, B, & C. This randomization procedure was performed in a double-blind manner, ensuring that both investigators and participants remained unaware of the group assignments, and the randomization process was blinded. Then, in order to reduce to zero the possibility of interfering in the selection of the intervention group by the researcher, 60 envelopes (containing number 1 to 60 and intervention group A, B, or C) were prepared at the time of the start of the study based on the order of entry of the eligible participants into the study, randomly from one of the envelopes was sent to The order will be opened and the placement of the patient in the intervention group will be determined.
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Blinding (investigator's opinion)
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Double blinded
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Blinding description
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Patients will be placed in one of three study groups and will be blinded to which study group they will be placed in. The drug is injected to the patient by the researcher. And the nurses will be blind to which study group they are included in.
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Placebo
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Used
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Assignment
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Parallel
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Other design features
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Ethics committees
1
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Ethics committee
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Approval date
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2024-04-06, 1403/01/18
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Ethics committee reference number
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IR.TUMS.HORCSCT.REC.1403.001
Health conditions studied
1
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Description of health condition studied
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Acute GvHD
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ICD-10 code
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D89.81
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ICD-10 code description
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Graft-versus-host disease
Primary outcomes
1
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Description
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Adverse events
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Timepoint
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day of injection, 1 and 2 weeks, 1, 3 and 6 months after the first injection
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Method of measurement
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History and clinical examination based on common terminological criteria for adverse events
Secondary outcomes
1
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Description
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Complete response rate
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Timepoint
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Day of injection, 1 and 2 weeks, 1, 3 and 6 months after the first injection
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Method of measurement
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Clinical examination
2
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Description
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Total survival rate
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Timepoint
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0 to 6 months
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Method of measurement
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Clinical evaluation
Intervention groups
1
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Description
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Intervention group: intravenous injection of a solution containing mesenchymal stem cells obtained from the human placenta is performed in 20 patients with acute graft-versus-host disease. Mesenchymal stem cells are injected at the rate of 1 million cells per kilogram of body weight in 200 cc of normal saline and 4 times at intervals of 3 days in patients. Mesenchymal stem cells are obtained in the clean room of Viraselul company and necessary quality control tests are performed on the final product. Treatment follow-up is done in the first and second week and in the first, third and sixth months after the injection.
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Category
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Treatment - Drugs
2
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Description
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Intervention group: intravenous injection of a solution containing exosome of mesenchymal stem cells obtained from human placenta is performed in 20 patients with acute graft-versus-host disease. Exosome of mesenchymal stem cells is injected in the amount of 1.2 x 10^12 exosomes in 50 cc of normal saline and 4 times with an interval of every 3 days in patients. Mesenchymal stem cells are obtained in the clean room of Viraselul company and necessary quality control tests are performed on the final product. Treatment follow-up is done in the first and second week and in the first, third and sixth months after the injection.
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Category
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Treatment - Drugs
3
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Description
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Control group: Ruxolitinib in 20 patients, NanoAlvand company, 5 mg twice daily, oral, 0 to 28 days after injection
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Category
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Treatment - Drugs
1
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Sponsor
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Grant name
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Grant code / Reference number
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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Tehran University of Medical Sciences
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Proportion provided by this source
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100
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Public or private sector
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Public
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Academic
Sharing plan
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Deidentified Individual Participant Data Set (IPD)
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Yes - There is a plan to make this available
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Study Protocol
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Yes - There is a plan to make this available
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Statistical Analysis Plan
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Yes - There is a plan to make this available
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Informed Consent Form
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Yes - There is a plan to make this available
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Clinical Study Report
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Yes - There is a plan to make this available
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Analytic Code
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Yes - There is a plan to make this available
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Data Dictionary
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Yes - There is a plan to make this available
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Title and more details about the data/document
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Clinical study report in the form of an article
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When the data will become available and for how long
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The access period starts 6 months after the results are published
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To whom data/document is available
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Researchers working in academic and scientific institutions
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Under which criteria data/document could be used
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Access to data and by request via email
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From where data/document is obtainable
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bajouri.md@gmail.com
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What processes are involved for a request to access data/document
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Within one month after the request, your request will be reviewed and the result will be announced.
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Comments
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