RecruitingInterventionalPhase 2

A Phase II Randomized Trial to Optimize GVHD Prophylaxis After Allogeneic Hematopoietic Cell Transplantation in Older Adults With Hematological Malignancies: the PROMISE Trial

NCT ID: NCT06799195Sponsor: University of NebraskaLast updated: 2025-12-15

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).

Arms & interventions

DrugAttenuated-dose Cyclophosphamide
Cyclophosphamide administered at an attenuated dose of 25 mg/kg on days +3 and +4 post-transplant for GVHD prophylaxis.
DrugHigh-dose Cyclophosphamide
Cyclophosphamide administered at the standard high dose of 50 mg/kg on days +3 and +4 post-transplant for GVHD prophylaxis.
DrugSirolimus
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.
DrugMycophenolate Mofetil (MMF)
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.

Outcome measures

Primary

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

Change in Karnofsky Performance Scale
Time frame: Baseline and 3 months post-transplant
Change in Activities of Daily Living
Time frame: Baseline and 3 months post-transplant
Change in Instrumental Activities of Daily Living
Time frame: Baseline and 3 months post-transplant
Change in Fried Frailty Index
Time frame: Baseline and 3 months post-transplant
Change in Clock-in-the-Box Test
Time frame: Baseline and 3 months post-transplant
Change in History of Falls
Time frame: Baseline and 3 months post-transplant
Change in Body Mass Index
Time frame: Baseline and 3 months post-transplant
Change in Geriatric Depression Scale-15
Time frame: Baseline and 3 months post-transplant
Gaft-Versus-Host Disease-Free, Relapse-Free Survival
Time frame: From date of transplant to 1 year post-transplant
Overall Survival at 1 Year Post-Transplant and Event-Free Survival
Time frame: From date of transplant to 1 year post-transplant
Cumulative Incidence of Transplant-Related Mortality
Time frame: From date of transplant to 1 year post-transplant
Cumulative Incidence of Grade II-IV Acute GVHD
Time frame: From date of transplant to 1 year post-transplant
Cumulative Incidence of Chronic GVHD
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
Time frame: From date of transplant to day +28 and day +100 post-transplant
Incidence of Grade III or Higher Adverse Events
Time frame: From date of transplant to day +100 post-transplant
Cumulative Incidence of Grade II or Higher Infections
Time frame: From date of transplant to 6 months post-transplant

Eligibility criteria

Sex: AllAge: 60 Years and olderHealthy volunteers: No

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.

Study locations (1)

University of Nebraska Medical Center

Omaha, Nebraska, 68198

Recruiting

Taylor Johnson · Contact

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

A · Contact

Moataz Ellithi, MBChB · Principal Investigator

References

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