Optimizing GVHD Prophylaxis After Allogeneic Hematopoietic Cell Transplantation

Phase 2RecruitingNCT06799195

University of Nebraska126 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

126

Conditions

Hematological Malignancies Graft-versus-Host Disease (GVHD)

Interventions

Attenuated-dose CyclophosphamideDRUG

Cyclophosphamide administered at an attenuated dose of 25 mg/kg on days +3 and +4 post-transplant for GVHD prophylaxis.

High-dose CyclophosphamideDRUG

Cyclophosphamide administered at the standard high dose of 50 mg/kg on days +3 and +4 post-transplant for GVHD prophylaxis.

SirolimusDRUG

Sirolimus is started on day +5 with a loading dose of 6 mg, followed by a maintenance dose of 2 mg daily, adjusted to target trough levels of 8-12 ng/mL. Sirolimus taper is recommended to start at day +90 and to be completed by day +180, provided there is no evidence of acute GVHD.

Eligibility

Sex: ALLMin age: 60 Years

Medical Language ↔ Plain English

Inclusion criteria: * Adults aged 60 years or older * Diagnosis of a hematological malignancy or other serious hematological disorder that requires an allogeneic hematopoietic cell transplantation * Planned to receive any reduced-intensity conditioning regimen (any graft source is acceptable) and availability of human leukocyte antigen (HLA)-matched donor at HLA loci A, B, C, and HLA-DR beta chain antigen (DRB1) * Karnofsky Performance Status (KPS) of 70% or higher. Exclusion criteria: * Previous history of one or more prior allogeneic stem cell transplants (i.e., second or third allogeneic transplant) * Planned use of high doses of cyclophosphamide (e.g., a total cyclophosphamide dose of approximately 50 mg/kg or more) as part of the conditioning regimen prior to allogeneic stem cell transplant. A lower dose of cyclophosphamide (e.g., fludarabine, cyclophosphamide, and low-dose total body irradiation regimen that uses 2 doses of cyclophosphamide at 14.5 mg/kg) is acceptable. * Known diagnosis of liver cirrhosis or other advanced liver disease that may impact cyclophosphamide metabolism. * Diagnosis of myelofibrosis * Creatinine clearance less than 40 mL/min/1.73 m², which may increase the risk of hemorrhagic cystitis with post-transplant cyclophosphamide (PTCy) * Systolic cardiac dysfunction with an ejection fraction of less than 45%. * Use of a haploidentical or mismatched donor. * Any other condition judged by the physician to increase the risk of toxicities associated with PTCy.

Locations (1)

University of Nebraska Medical Center

Omaha, Nebraska, United States

RECRUITING

Outcomes

Primary Outcomes

Change in Health-Related Quality of Life as Measured by Functional Assessment of Cancer Therapy-Bone Marrow Transplantation

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.

Time frame: Baseline and 3 months post-transplant

Secondary Outcomes

Change in Karnofsky Performance Scale

Karnofsky Performance Scale (KPS) is a validated tool ranging from 0 (death) to 100 (normal activity). Higher scores indicate better functional status.

Time frame: Baseline and 3 months post-transplant

Change in Activities of Daily Living

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.

Time frame: Baseline and 3 months post-transplant

Change in Instrumental Activities of Daily Living

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.

Time frame: Baseline and 3 months post-transplant

Change in Fried Frailty Index

The Fried Frailty Index assesses five components (weight loss, exhaustion, grip strength, walking speed, and physical activity). A higher total score indicates greater frailty.

Central Contacts

Taylor Johnson

CONTACT

402-559-4596 taylora.johnson@unmc.edu

IIT OFFICE

CONTACT

402-559-4596 iitoffice@unmc.edu

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

MMF is started on day +5 at a dose of 15 mg/kg per dose (maximum 1 g per dose) three times daily. MMF is generally discontinued by day +35 in the absence of GVHD.

Time frame: Baseline and 3 months post-transplant

Change in Clock-in-the-Box Test

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.

Time frame: Baseline and 3 months post-transplant

Change in History of Falls

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.

Time frame: Baseline and 3 months post-transplant

Change in Body Mass Index

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.

Time frame: Baseline and 3 months post-transplant

Change in Geriatric Depression Scale-15

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.

Time frame: Baseline and 3 months post-transplant

Gaft-Versus-Host Disease-Free, Relapse-Free Survival

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.

Time frame: From date of transplant to 1 year post-transplant

Overall Survival at 1 Year Post-Transplant and Event-Free Survival

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

Time frame: From date of transplant to 1 year post-transplant

Cumulative Incidence of Transplant-Related Mortality

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.

Time frame: From date of transplant to 1 year post-transplant

Cumulative Incidence of Grade II-IV Acute GVHD

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.

Time frame: From date of transplant to 1 year post-transplant

Cumulative Incidence of Chronic GVHD

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.

Time frame: From date of transplant to 1 year post-transplant

To determine the cumulative incidence and kinetics of hematologic recovery (neutrophil and platelet) among the two treatment arms

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.

Time frame: From date of transplant to day +28 and day +100 post-transplant

Incidence of Grade III or Higher Adverse Events

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.

Time frame: From date of transplant to day +100 post-transplant

Cumulative Incidence of Grade II or Higher Infections

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.

Time frame: From date of transplant to 6 months post-transplant