Optimizing GVHD Prophylaxis After Allogeneic Hematopoietic Cell Transplantation

ConditionsHematological Malignancies Graft-versus-Host Disease (GVHD)

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age60+

SponsorUniversity of Nebraska

About this trial

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 criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

Attenuated-dose Cyclophosphamide
Drug
Cyclophosphamide administered at an attenuated dose of 25 mg/kg on days +3 and +4 post-transplant for GVHD prophylaxis.
High-dose Cyclophosphamide
Drug
Cyclophosphamide administered at the standard high dose of 50 mg/kg on days +3 and +4 post-transplant for GVHD prophylaxis.
Sirolimus
Drug
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.
Mycophenolate Mofetil (MMF)
Drug
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.

Treatment groups

126 Participants

are divided into 2 treatment groups

Group A: Attenuated-dose post-transplant cyclophosphamide (PTCy) ArmExperimental treatment 3 interventions

Group B: High-dose post-transplant cyclophosphamide (PTCy) Arm: Standard of CareActive comparator 3 interventions

Trial 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