Optimizing GVHD Prophylaxis After Allogeneic Hematopoietic Cell Transplantation
A Phase II Randomized Trial to Optimize GVHD Prophylaxis After Allogeneic Hematopoietic Cell Transplantation in Older Adults With Hematological Malignancies: the PROMISE Trial
University of Nebraska
126 participants
Jun 23, 2025
INTERVENTIONAL
Conditions
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.
Eligibility
Inclusion Criteria4
- 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 Criteria8
- 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.
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Interventions
Cyclophosphamide administered at an attenuated dose of 25 mg/kg on days +3 and +4 post-transplant for GVHD prophylaxis.
Cyclophosphamide administered at the standard high dose of 50 mg/kg on days +3 and +4 post-transplant for GVHD prophylaxis.
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.
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.
Locations(1)
View Full Details on ClinicalTrials.gov
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NCT06799195