Improving GVHD prevention after donor stem cell transplant
A Phase II Randomized Trial to Optimize GVHD Prophylaxis After Allogeneic Hematopoietic Cell Transplantation in Older Adults With Hematological Malignancies: the PROMISE Trial
This study will test whether a lower dose versus the standard dose of post-transplant cyclophosphamide, given with sirolimus and MMF, improves quality of life for people aged 60 and older having a reduced-intensity allogeneic stem cell transplant.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 126 (estimated) |
| Ages | 60 Years and up |
| Sex | All |
| Sponsor | University of Nebraska Academic / other |
| Drugs / interventions | cyclophosphamide, fludarabine |
| Locations | 1 site (Omaha, Nebraska) |
| Trial ID | NCT06799195 on ClinicalTrials.gov |
What this trial studies
This single-center, randomized Phase 2 study will enroll 126 participants aged 60 and older with hematologic malignancies undergoing reduced-intensity allogeneic hematopoietic cell transplantation. Participants are randomized to receive either the standard high dose or an attenuated dose of post-transplant cyclophosphamide in addition to sirolimus and mycophenolate mofetil for GVHD prophylaxis. The trial will follow patients for health-related quality of life using FACT-BMT and a battery of functional measures (KPS, ADLs/IADLs, frailty measures, cognitive clock test, BMI, falls, GDS-15) as well as monitoring for acute and chronic GVHD, relapse, survival, and treatment toxicities using CTCAE v5.0. The primary focus is on post-transplant HRQoL and functional outcomes in an older transplant population.
Who should consider this trial
Good fit: Ideal candidates are adults aged 60 or older with a hematologic malignancy who are planned for a reduced-intensity allogeneic transplant with an HLA-matched donor and have a Karnofsky Performance Status of 70% or higher.
Not a fit: Patients younger than 60, those planned for myeloablative conditioning or who have had a prior allogeneic transplant, or those without an HLA-matched donor are unlikely to benefit from or be eligible for this protocol.
Why it matters
Potential benefit: If successful, the approach could reduce treatment-related toxicity and improve post-transplant quality of life and functional independence for older transplant recipients.
How similar studies have performed: Post-transplant cyclophosphamide is an established GVHD prevention strategy, but using an attenuated post-transplant dose specifically to improve quality of life in older adults is a relatively novel approach with limited direct evidence.
Eligibility criteria
Show full inclusion / exclusion criteria
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.
Where this trial is running
Omaha, Nebraska
- University of Nebraska Medical Center — Omaha, Nebraska, United States (Recruiting)
Study contacts
- Principal investigator: Moataz Ellithi, MBChB — University of Nebraska
- Study coordinator: Taylor Johnson
- Email: taylora.johnson@unmc.edu
- Phone: 402-559-4596
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.