Comparison of PT-Cy at a Dose of 25 mg/kg/Day and PT-Cy at a Dose of 50 mg/kg/Day in GVHD Prophylaxis

Study Overview
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Brief Summary
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This is a two arm open label phase III clinical trial. Adult patients with hematological malignancies undergoing allogeneic HSCT from any donor are eligible for the study if they meet the standard criteria defined in the investigator's institutional standard operation procedures (SOPs), meet all inclusion criteria, and do not satisfy any exclusion criteria. Patients will receive reduced-intensity conditioning regimen of fludarabine, busulfan (treosulfan). Patients will receive PTCy at different dose (25 mg/kg/day vs 50 mg/kg/day on day +3,+4 in combination with calcineurin inhibitors and mofetil mycophenolate) as GvHD prophylaxis.

Official Title
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A Randomized, Open-label, Single-center Study Comparing Cyclophosphamide at a Dose of 25 mg/kg/Day and Cyclophosphamide at a Dose of 50 mg/kg/Day in Graft Versus Host Disease Prophylaxis

Conditions
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Graft Versus Host Disease, Hematologic Malignancy, Cyclophosphamide Adverse Reaction

Intervention / Treatment
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* Drug: Post-transplantation Cyclophosphamide at dose 25 mg/kg/day
* Drug: Post-transplantation Cyclophosphamide at dose 50 mg/kg/day


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who have an indication for allogeneic hematopoietic stem cell transplantation Exclusion Criteria: Uncontrolled bacterial or fungal infection at the time of enrollment Requirement for vasopressor support at the time of enrollment Karnofsky index <30% Pregnancy Somatic or psychiatric disorder making the patient unable to sign informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cyclophosphamide on day +3,+4 at dose 50 mg/kg/day<br>Post-transplantation Cyclophosphamide will be apply for GVHD prophylaxis on day +3,+4 at dose 50 mg/kg/day in combination with cyclosporine A at 3 mg/kg/day from day +5 and mycophenolate mofetil at dose 30-45mg/kg/day from day +5. | Drug: Post-transplantation Cyclophosphamide at dose 50 mg/kg/day<br>* Post-transplantation Cyclophosphamide will be apply for GVHD prophylaxis on day +3,+4 at dose 50 mg/kg/day in combination with cyclosporine A at 3 mg/kg/day from day +5 and mycophenolate mofetil at dose 30-45mg/kg/day from day +5.<br>* Other names: Cyphos;|
| Experimental: Cyclophosphamide on day +3,+4 at dose 25 mg/kg/day<br>Post-transplantation Cyclophosphamide will be apply for GVHD prophylaxis on day +3,+4 at dose 25 mg/kg/day in combination with cyclosporine A at 3 mg/kg/day from day +5 and mycophenolate mofetil at dose 30-45mg/kg/day from day +5. | Drug: Post-transplantation Cyclophosphamide at dose 25 mg/kg/day<br>* Post-transplantation Cyclophosphamide will be apply for GVHD prophylaxis on day +3,+4 at dose 25 mg/kg/day in combination with cyclosporine A at 3 mg/kg/day from day +5 and mycophenolate mofetil at dose 30-45mg/kg/day from day +5.<br>* Other names: Cyphos;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of acute graft-versus-host disease, grades II-IV | MAGIC criteria | 180 days | 
| Incidence of chronic GVHD, moderate and severe (NIH criteria) | NIH criteria | 365 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival analysis | Kaplan-Meier survival analysis | 365 days | 
| Event-free survival analysis | Kaplan-Meier survival analysis | 365 days | 
| Non-relapse mortality analysis | Kaplan-Meier survival analysis, competing risk analysis | 365 days | 
| Incidence of graft failure and poor graft function | Kaplan-Meier survival analysis, competing risk analysis | 365 days | 
| Incidence of 30-Day Readmission | Kaplan-Meier survival analysis, competing risk analysis | 365 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Allogeneic transplantation, Graft-versus-host-disease prophylaxis, Post-transplant cyclophosphamide