CY25: 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

Sponsor

National Research Center for Hematology, Russia (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05158608

Collaborator

(none)

100

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Graft Versus Host Disease Hematologic Malignancy Cyclophosphamide Adverse Reaction	Drug: Post-transplantation Cyclophosphamide at dose 25 mg/kg/day Drug: Post-transplantation Cyclophosphamide at dose 50 mg/kg/day	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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

Anticipated Study Start Date :

Jan 1, 2022

Anticipated Primary Completion Date :

Jan 1, 2024

Anticipated Study Completion Date :

Jan 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Cyclophosphamide on day +3,+4 at dose 50 mg/kg/day 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 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. Other Names: Endoxan Cyphos
Experimental: Cyclophosphamide on day +3,+4 at dose 25 mg/kg/day 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 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. Other Names: Endoxan Cyphos

Arm

Intervention/Treatment

Active Comparator: Cyclophosphamide on day +3,+4 at dose 50 mg/kg/day

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

Other Names:

Endoxan

Cyphos

Experimental: Cyclophosphamide on day +3,+4 at dose 25 mg/kg/day

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

Other Names:

Endoxan

Cyphos

Outcome Measures

Primary Outcome Measures

Incidence of acute graft-versus-host disease, grades II-IV [180 days]
MAGIC criteria
Incidence of chronic GVHD, moderate and severe (NIH criteria) [365 days]
NIH criteria

Secondary Outcome Measures

Overall survival analysis [365 days]
Kaplan-Meier survival analysis
Event-free survival analysis [365 days]
Kaplan-Meier survival analysis
Non-relapse mortality analysis [365 days]
Kaplan-Meier survival analysis, competing risk analysis
Incidence of graft failure and poor graft function [365 days]
Kaplan-Meier survival analysis, competing risk analysis
Incidence of 30-Day Readmission [365 days]
Kaplan-Meier survival analysis, competing risk analysis

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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