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 (CY25)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Hematologic Malignancy; Graft Versus Host Disease; Cyclophosphamide Adverse Reaction
• Intervention / Treatment: Drug: Post-transplantation Cyclophosphamide at dose 50 mg/kg/day; Drug: Post-transplantation Cyclophosphamide at dose 25 mg/kg/day

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Mikhail Drokov, MD, Ph.D; Phone Number: +74956149042; Email: mdrokov@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Research Center for Hematology, Russia
• Investigators: Principal Investigator: Elena Parovichnikova, MD, D.Sc, National Research Center for Hematology

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2022
• Primary Completion (Anticipated): January 1, 2024
• Study Completion (Anticipated): January 1, 2025

Study Registration Dates

• First Submitted: December 12, 2021
• First Submitted That Met QC Criteria: December 12, 2021
• First Posted (Actual): December 15, 2021

Study Record Updates

• Last Update Posted (Actual): January 11, 2022
• Last Update Submitted That Met QC Criteria: December 17, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Allogeneic transplantation; Graft-versus-host-disease prophylaxis; Post-transplant cyclophosphamide
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms; Neoplasms by Site; Hematologic Diseases; Hematologic Neoplasms; Graft vs Host Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide
• Other Study ID Numbers: CY25

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No