Optimizing GVHD Prophylaxis After Allogeneic Hematopoietic Cell Transplantation

Phase 2

Not yet recruiting

• Conditions: Hematological Malignancies; Graft-versus-Host Disease (GVHD)
• Interventions: Drug: Attenuated-dose Cyclophosphamide; Drug: High-dose Cyclophosphamide; Drug: Sirolimus; Drug: Mycophenolate Mofetil (MMF)

• Registration Number: NCT06799195
• Lead Sponsor: University of Nebraska

Brief Summary

This study will compare post-transplant health-related quality of life following the use of standard versus attenuated dose of post-transplant cyclophosphamide in addition to two-drug graft-versus-host disease (GVHD) prophylaxis among recipients of allogeneic hematopoietic stem cell transplant.

Detailed Description

This is a single-center phase II study of 126 participants (63 per arm) with hematological malignancies. Participants will be randomized to receive high doses (standard arm) or attenuated doses of cyclophosphamide in addition to two-drug GVHD prophylaxis. Participants will be monitored for health-related quality of life \[Functional Assessment of Cancer Therapy-Bone Marrow Transplant, FACT-BMT(1)\], functional outcomes (Karnofsky Performance Scale (KPS), activities of daily living, instrumental activities of daily living, Clock-in-the-Box Test, Fried Frailty Index, fall history, BMI, and Geriatric Depression Scale-15, GVHD, relapse, survival, and toxicities (using Common Terminology Criteria for Adverse Events, CTCAE version 5.0).

Study Timeline

• Study First Submitted: 2025-01-15
• Study First Submitted QC: 2025-01-22
• Study First Posted: 2025-01-29
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-21
• Last Update Posted: 2025-04-24
• Study Start: 2025-05
• Primary Completion: 2031-02
• Study Completion: 2031-11

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 126

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Attenuated-dose post-transplant cyclophosphamide (PTCy) Arm	Attenuated-dose Cyclophosphamide	Participants will receive attenuated-dose post-transplant cyclophosphamide (PTCy) at 25 mg/kg on days +3 and +4 after allogeneic hematopoietic stem cell transplantation. This is in addition to sirolimus and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis.
Attenuated-dose post-transplant cyclophosphamide (PTCy) Arm	Sirolimus	Participants will receive attenuated-dose post-transplant cyclophosphamide (PTCy) at 25 mg/kg on days +3 and +4 after allogeneic hematopoietic stem cell transplantation. This is in addition to sirolimus and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis.
Attenuated-dose post-transplant cyclophosphamide (PTCy) Arm	Mycophenolate Mofetil (MMF)	Participants will receive attenuated-dose post-transplant cyclophosphamide (PTCy) at 25 mg/kg on days +3 and +4 after allogeneic hematopoietic stem cell transplantation. This is in addition to sirolimus and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis.
High-dose post-transplant cyclophosphamide (PTCy) Arm: Standard of Care	High-dose Cyclophosphamide	Participants will receive high-dose post-transplant cyclophosphamide (PTCy) at 50 mg/kg on days +3 and +4 after allogeneic hematopoietic stem cell transplantation. This is in addition to sirolimus and mycophenolate mofetil (MMF) for GVHD prophylaxis.
High-dose post-transplant cyclophosphamide (PTCy) Arm: Standard of Care	Sirolimus	Participants will receive high-dose post-transplant cyclophosphamide (PTCy) at 50 mg/kg on days +3 and +4 after allogeneic hematopoietic stem cell transplantation. This is in addition to sirolimus and mycophenolate mofetil (MMF) for GVHD prophylaxis.
High-dose post-transplant cyclophosphamide (PTCy) Arm: Standard of Care	Mycophenolate Mofetil (MMF)	Participants will receive high-dose post-transplant cyclophosphamide (PTCy) at 50 mg/kg on days +3 and +4 after allogeneic hematopoietic stem cell transplantation. This is in addition to sirolimus and mycophenolate mofetil (MMF) for GVHD prophylaxis.

Primary Outcome Measures

Name	Time	Method
Change in Health-Related Quality of Life as Measured by Functional Assessment of Cancer Therapy-Bone Marrow Transplantation	Baseline and 3 months post-transplant	The health-related quality of life will be assessed using the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) trial outcome index (TOI). The FACT-BMT is a validated, patient-reported questionnaire that measures physical and functional well-being specifically in bone marrow transplant recipients. Higher scores indicate better quality of life. The primary outcome is to compare the FACT-BMT TOI scores between the attenuated-dose PTCy arm and the high-dose PTCy arm at 3 months post-transplant.

Secondary Outcome Measures

Name	Time	Method
Change in Karnofsky Performance Scale	Baseline and 3 months post-transplant	Karnofsky Performance Scale (KPS) is a validated tool ranging from 0 (death) to 100 (normal activity). Higher scores indicate better functional status.
Change in Activities of Daily Living	Baseline and 3 months post-transplant	Activities of Daily Living (ADL) measures basic self-care tasks such as bathing and dressing. The typical total score ranges from 0 to 6, with higher scores indicating better functional status.
Change in Instrumental Activities of Daily Living	Baseline and 3 months post-transplant	Change in Instrumental Activities of Daily Living (IADL) assesses more complex tasks (e.g., handling finances). Total scores typically range from 0 to 8 or 0 to 14 (depending on the version), with higher scores indicating greater independence.
Change in Fried Frailty Index	Baseline and 3 months post-transplant	The Fried Frailty Index assesses five components (weight loss, exhaustion, grip strength, walking speed, and physical activity). A higher total score indicates greater frailty.
Change in Clock-in-the-Box Test	Baseline and 3 months post-transplant	This is a brief test of visuospatial and executive function, typically scored on accuracy of clock drawing/placement (range 0-8). Higher scores suggest better cognitive performance.
Change in History of Falls	Baseline and 3 months post-transplant	The number of falls, if any, will be collected since baseline. Results will be analyzed as the proportion of participants experiencing ≥1 fall over the time frame, or as the difference in mean (or median) number of falls between arms.
Change in Body Mass Index	Baseline and 3 months post-transplant	Body Mass Index (BMI) is calculated as weight (kg) / \[height (m)\]² (kg/m²). Higher or lower values do not necessarily indicate "better" or "worse" status by themselves but will be compared between arms for changes from baseline.
Change in Geriatric Depression Scale-15	Baseline and 3 months post-transplant	The Geriatric Depression Scale-15 (GDS-15) is a 15-item screening tool for depression in older adults (scores 0-15). Higher scores indicate more severe depression.
Gaft-Versus-Host Disease-Free, Relapse-Free Survival	From date of transplant to 1 year post-transplant	Graft-Versus-Host Disease (GRFS) is defined as the time from transplant to the first occurrence of grade III-IV acute GVHD, chronic GVHD requiring systemic immune suppression, disease relapse or progression, or death from any cause. An event is counted when any of these conditions are met. The GRFS at 1 year post-transplant will be compared between the two treatment arms.
Overall Survival at 1 Year Post-Transplant and Event-Free Survival	From date of transplant to 1 year post-transplant	Overall Survival (OS) is defined as survival from the date of transplant until death from any cause. Event-Free Survival (EFS) is defined as survival from the date of transplant without disease relapse or progression. The study will compare the proportion of participants alive (for OS) and without relapse or progression (for EFS) at 1 year post-transplant between the two treatment arms
Cumulative Incidence of Transplant-Related Mortality	From date of transplant to 1 year post-transplant	Transplant-related mortality (TRM) is defined as death from causes other than disease relapse or progression. The study will estimate and compare the cumulative incidence of TRM at 1 year post-transplant between the two treatment arms.
Cumulative Incidence of Grade II-IV Acute GVHD	From date of transplant to 1 year post-transplant	Acute graft-versus-host disease (GVHD) of grade II-IV is assessed using the Mount Sinai acute GVHD grading system. The study will estimate and compare the cumulative incidence of grade II-IV acute GVHD at 1 year post-transplant between the two treatment arms.
Cumulative Incidence of Chronic GVHD	From date of transplant to 1 year post-transplant	Chronic GVHD is assessed using the NIH chronic GVHD grading system, which includes both classical chronic GVHD and overlap syndrome. The study will estimate and compare the cumulative incidence of chronic GVHD at 1 year post-transplant between the two treatment arms.
To determine the cumulative incidence and kinetics of hematologic recovery (neutrophil and platelet) among the two treatment arms	From date of transplant to day +28 and day +100 post-transplant	Hematologic recovery is evaluated by time to neutrophil engraftment (absolute neutrophil count ≥ 500/mm³ for three consecutive days) and platelet engraftment (platelet count ≥ 20,000/mm³ or ≥ 50,000/mm³ without transfusion for seven days). The study will describe and compare the cumulative incidence and kinetics of neutrophil and platelet recovery by days +28 and +100 post-transplant between the two treatment arms.
Incidence of Grade III or Higher Adverse Events	From date of transplant to day +100 post-transplant	Adverse events will be graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The study will assess and compare the incidence of grade III or higher adverse events by day +100 post-transplant between the two treatment arms.
Cumulative Incidence of Grade II or Higher Infections	From date of transplant to 6 months post-transplant	Infections will be graded according to Blood and Marrow Transplant Clinical Trials Network (BMT CTN) criteria. The study will estimate and compare the cumulative incidence of grade II or higher infections by 6 months post-transplant between the two treatment arms.

Trial Locations

Locations (1)

University of Nebraska Medical Center; 🇺🇸 Omaha, Nebraska, United States