Evaluation of Post-transplant Cyclophosphamide as an Addition to Standard Graft-versus-Host Disease Prophylaxis in Allogeneic Hematopoietic Stem Cell Transplant Recipients with Parous Female Donors: A Phase III Non-randomized Clinical Trial
Comparing the incidence of grade 3-4 acute graft-versus-host disease (GVHD) and extensive chronic GVHD between the intervention and control groups.
Design
Non-randomized phase 3 clinical trial with historical control group
Settings and conduct
This study will be conducted at the Research Institute for Oncology, Hematology, and Cell Therapy throughout 2024. Patients in the intervention group will receive intravenous cyclophosphamide at a dosage of 40 mg/kg/day on days +3 and +4, in addition to the center's current GVHD prophylaxis regimen. Furthermore, all patients will also receive intravenous cyclophosphamide at a dose of 40 mg/kg/day.
Participants/Inclusion and exclusion criteria
Adult patients diagnosed with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) who are in complete remission (CR) and are undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT) from an HLA-identical sibling donor will be enrolled in the study. Eligible participants must have a history of previous pregnancy or miscarriage and no prior transplant history.
Intervention groups
In the control group, patients undergoing stem cell transplantation will receive the center's standard GVHD prophylaxis regimen, which includes intravenous cyclosporine at a dosage of 3 mg/kg starting on day +5 and continuing until oral tolerance is established. Additionally, they will receive methotrexate (MTX) at a dose of 10 mg/m² on day +1, followed by 6 mg/m² on days +3, +6, and +11.
In the intervention group, patients will receive intravenous cyclophosphamide at a dosage of 40 mg/kg/day on days +3 and +4, in conjunction with the center's current GVHD prophylaxis regimen.
Main outcome variables
Cumulative incidence of grade 3-4 acute GVHD; Cumulative incidence of extensive chronic GVHD
General information
Reason for update
Acronym
PTCy-GVHD
IRCT registration information
IRCT registration number:IRCT20140818018842N44
Registration date:2024-12-30, 1403/10/10
Registration timing:prospective
Last update:2024-12-30, 1403/10/10
Update count:0
Registration date
2024-12-30, 1403/10/10
Registrant information
Name
Leyla Sharifi Aliabadi
Name of organization / entity
Research Institute for Hematology, Oncology and Stem Cell Transplantation,Tehran University of Medic
Country
Iran (Islamic Republic of)
Phone
+98 21 8490 2635
Email address
ctu@sina.tums.ac.ir
Recruitment status
recruiting
Funding source
Expected recruitment start date
2025-01-19, 1403/10/30
Expected recruitment end date
2026-03-20, 1404/12/29
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Evaluation of Post-transplant Cyclophosphamide as an Addition to Standard Graft-versus-Host Disease Prophylaxis in Allogeneic Hematopoietic Stem Cell Transplant Recipients with Parous Female Donors: A Phase III Non-randomized Clinical Trial
Public title
Exploring the Benefits of Adding a New Drug, Post-transplant Cyclophosphamide, to Standard Treatment for Preventing Transplant Complications in Patients Receiving Stem Cells from Female Donors with a History of Pregnancy
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Adult patients between 18 and 55 years of age
Diagnosed with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL)
In complete remission (CR)
Undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT) from a human leukocyte antigen (HLA)-identical sibling donor
Donors with a history of previous pregnancy or miscarriage
ECOG performance status of 2 or less
Left ventricular ejection fraction (LVEF) of 45% or greater
Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) of at least 60% of predicted values
Adequate liver function, defined as total bilirubin levels of 3.0 mg/dL or less or the absence of clinically significant liver disease
Exclusion criteria:
Prior history of allogeneic or autologous transplantation
CD3 count less than 150 x 10^6
Age
From 18 years old to 65 years old
Gender
Both
Phase
3
Groups that have been masked
No information
Sample size
Target sample size:
120
Randomization (investigator's opinion)
Not randomized
Randomization description
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Other
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Ethic committee of Hematology- Oncology and cell therapy Research Institute, Tehran University of Me
Street address
Shariati Hospital, Jalal-e-Al-e-Ahmad Hwy
City
Tehran
Province
Tehran
Postal code
1411713135
Approval date
2024-11-27, 1403/09/07
Ethics committee reference number
IR.TUMS.HORCSCT.REC.1403.045
Health conditions studied
1
Description of health condition studied
Acute myeloblastic leukaemia
ICD-10 code
C92.0
ICD-10 code description
Acute myeloblastic leukemia
2
Description of health condition studied
Acute lymphoblastic leukaemia
ICD-10 code
C91.0
ICD-10 code description
Acute lymphoblastic leukemia [ALL]
Primary outcomes
1
Description
Cumulative incidence of grade 3-4 acute GVHD
Timepoint
until 100 days After the intervention
Method of measurement
Visiting the patient and lab tests
2
Description
Cumulative incidence of extensive chronic GVHD
Timepoint
From 100 days following the intervention.
Method of measurement
Visiting the patient and lab tests
Secondary outcomes
1
Description
overall survival
Timepoint
Monthly for 12 months after transplantation
Method of measurement
Visiting the patient
2
Description
One-year relapse rate
Timepoint
Monthly for 12 months after transplantation
Method of measurement
Visiting the patient and performing monthly lab tests in outpatient clinique
3
Description
Disease-free survival
Timepoint
Monthly for 12 months after transplantation
Method of measurement
Bone marrow biopsy
4
Description
GvHD-free survival
Timepoint
Monthly for 12 months after transplantation
Method of measurement
Visiting the patient in person and performing monthly lab tests in outpatient clinique
Intervention groups
1
Description
Intervention group: patients undergoing stem cell transplantation will receive the center's standard GVHD prophylaxis regimen (which includes intravenous cyclosporine at a dosage of 3 mg/kg starting on day +5 and continuing until oral tolerance and methotrexate (MTX) at a dose of 10 mg/m² on day +1, followed by 6 mg/m² on days +3, +6, and +11).In addition, patients will receive intravenous cyclophosphamide at a dosage of 40 mg/kg/day on days +3 and +4
Category
Treatment - Other
2
Description
Control group: In the control group, patients undergoing stem cell transplantation will receive the center's standard GVHD prophylaxis regimen, which includes intravenous cyclosporine at a dosage of 3 mg/kg starting on day +5 and continuing until oral tolerance is established. Additionally, they will receive methotrexate (MTX) at a dose of 10 mg/m² on day +1, followed by 6 mg/m² on days +3, +6, and +11
Category
Treatment - Other
Recruitment centers
1
Recruitment center
Name of recruitment center
Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences
Full name of responsible person
Maryam Barkhordar
Street address
Shariati Hospital, Jalal-e-Al-e-Ahmad Hwy
City
Tehran
Province
Tehran
Postal code
14117 13135
Phone
+98 21 8490 3681
Email
barkhordarm.n@gmail.com
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Ramin Kordi
Street address
Keshavarz Blvd.
City
Tehran
Province
Tehran
Postal code
1461884513
Phone
+98 912 697 2683
Email
ramin_kordi@tums.ac.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Tehran University of Medical Sciences
Proportion provided by this source
100
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic
Person responsible for general inquiries
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Maryam Barkhordar
Position
assistant professor
Latest degree
Subspecialist
Other areas of specialty/work
Hematology
Street address
Shariati Hospital, North Kargar Ave.
City
Tehran
Province
Tehran
Postal code
1411713135
Phone
0021 8490 3691
Fax
+98 21 8800 4140
Email
barkhordarm.n@gmail.com
Person responsible for scientific inquiries
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Maryam Barkhordar
Position
assistant professor
Latest degree
Subspecialist
Other areas of specialty/work
Hematology
Street address
Kargar-e-Shomali Ave.
City
Tehran
Province
Tehran
Postal code
1411713131
Phone
0021 8800 4140
Email
barkhordarm.n@gmail.com
Person responsible for updating data
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Leyla Sharifi Aliabadi
Position
Research Assistant
Latest degree
Master
Other areas of specialty/work
Epidemiology
Street address
Shariati Hospital, North Kargar Ave.
City
Tehran
Province
Tehran
Postal code
1411713131
Phone
+98 21 8490 2635
Fax
+98 21 8800 4140
Email
ctu@sina.tums.ac.ir
Sharing plan
Deidentified Individual Participant Data Set (IPD)
Undecided - It is not yet known if there will be a plan to make this available
Study Protocol
Undecided - It is not yet known if there will be a plan to make this available
Statistical Analysis Plan
Not applicable
Informed Consent Form
Undecided - It is not yet known if there will be a plan to make this available
Clinical Study Report
Not applicable
Analytic Code
Undecided - It is not yet known if there will be a plan to make this available
Data Dictionary
Undecided - It is not yet known if there will be a plan to make this available