Optimizing GVHD Prophylaxis After Allogeneic Hematopoietic Cell Transplantation (PTCYGVHD)

University of Nebraska

Status and phase: Enrolling; Phase 2

Conditions: Hematological Malignancies; Graft-versus-Host Disease (GVHD)

Treatments: Drug: Sirolimus; Drug: Attenuated-dose Cyclophosphamide; Drug: High-dose Cyclophosphamide; Drug: Mycophenolate Mofetil (MMF)

Study type: Interventional

Funder types: Other

Identifiers

NCT06799195

0094-25-FB

Details and patient eligibility

About

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.

Full 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).

Enrollment: 126 estimated patients

Sex: All

Ages: 60+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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126 participants in 2 patient groups

Attenuated-dose post-transplant cyclophosphamide (PTCy) Arm

Experimental group

Description:

Participants will receive attenuated-dose post-transplant cyclophosphamide (PTCy) at 25 mg/kg on days +3 and +4 after allogeneic hematopoietic stem cell transplantation. This is in addition to sirolimus and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis.

Treatment:

Drug: Mycophenolate Mofetil (MMF)

Drug: Attenuated-dose Cyclophosphamide

Drug: Sirolimus

High-dose post-transplant cyclophosphamide (PTCy) Arm: Standard of Care

Active Comparator group

Description:

Participants will receive high-dose post-transplant cyclophosphamide (PTCy) at 50 mg/kg on days +3 and +4 after allogeneic hematopoietic stem cell transplantation. This is in addition to sirolimus and mycophenolate mofetil (MMF) for GVHD prophylaxis.

Treatment:

Drug: Mycophenolate Mofetil (MMF)

Drug: High-dose Cyclophosphamide

Drug: Sirolimus