Optimizing GVHD Prophylaxis After Allogeneic Hematopoietic Cell Transplantation

NCT06799195 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 0094-25-FB
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

Allogeneic Hematopoietic Stem Cell Transplantation; GVHD Prophylaxis; Sirolimus; Mycophenolate Mofetil (MMF); Health-Related Quality of Life (HRQoL); Randomized Controlled Trial

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline and 3 months post-transplant

Secondary Outcomes (16)

• Change in Karnofsky Performance Scale

  Baseline and 3 months post-transplant

• Change in Activities of Daily Living

  Baseline and 3 months post-transplant

• Change in Instrumental Activities of Daily Living

  Baseline and 3 months post-transplant

• Change in Fried Frailty Index

  Baseline and 3 months post-transplant

• Change in Clock-in-the-Box Test

  Baseline and 3 months post-transplant

Study Arms (2)

Attenuated-dose post-transplant cyclophosphamide (PTCy) Arm

EXPERIMENTAL

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.

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

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

ACTIVE COMPARATOR

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.

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

Interventions

Attenuated-dose Cyclophosphamide DRUG

Cyclophosphamide administered at an attenuated dose of 25 mg/kg on days +3 and +4 post-transplant for GVHD prophylaxis.

Attenuated-dose post-transplant cyclophosphamide (PTCy) Arm

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.

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

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.

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

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.

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

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Nebraska: lead

Study Sites (1)

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

RECRUITING

Related Publications (4)

• Luznik L, Pasquini MC, Logan B, Soiffer RJ, Wu J, Devine SM, Geller N, Giralt S, Heslop HE, Horowitz MM, Jones RJ, Litzow MR, Mendizabal A, Muffly L, Nemecek ER, O'Donnell L, O'Reilly RJ, Palencia R, Schetelig J, Shune L, Solomon SR, Vasu S, Ho VT, Perales MA. Randomized Phase III BMT CTN Trial of Calcineurin Inhibitor-Free Chronic Graft-Versus-Host Disease Interventions in Myeloablative Hematopoietic Cell Transplantation for Hematologic Malignancies. J Clin Oncol. 2022 Feb 1;40(4):356-368. doi: 10.1200/JCO.21.02293. Epub 2021 Dec 2.

  PMID: 34855460 BACKGROUND

• Korngold R, Sprent J. Lethal graft-versus-host disease after bone marrow transplantation across minor histocompatibility barriers in mice. Prevention by removing mature T cells from marrow. J Exp Med. 1978 Dec 1;148(6):1687-98. doi: 10.1084/jem.148.6.1687.

  PMID: 363972 BACKGROUND

• Wingard JR, Majhail NS, Brazauskas R, Wang Z, Sobocinski KA, Jacobsohn D, Sorror ML, Horowitz MM, Bolwell B, Rizzo JD, Socie G. Long-term survival and late deaths after allogeneic hematopoietic cell transplantation. J Clin Oncol. 2011 Jun 1;29(16):2230-9. doi: 10.1200/JCO.2010.33.7212. Epub 2011 Apr 4.

  PMID: 21464398 BACKGROUND

• McQuellon RP, Russell GB, Cella DF, Craven BL, Brady M, Bonomi A, Hurd DD. Quality of life measurement in bone marrow transplantation: development of the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) scale. Bone Marrow Transplant. 1997 Feb;19(4):357-68. doi: 10.1038/sj.bmt.1700672.

  PMID: 9051246 BACKGROUND

MeSH Terms

Conditions

Hematologic Neoplasms; Graft vs Host Disease

Interventions

Cyclophosphamide; Sirolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Study Officials

• Moataz Ellithi, MBChB

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Taylor Johnson

CONTACT

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

IIT OFFICE

CONTACT

402-559-4596; iitoffice@unmc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Not applicable; the study is open-label.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single-center, randomized, phase II trial comparing two graft-versus-host disease (GVHD) prophylaxis regimens in older adults undergoing allogeneic hematopoietic stem cell transplantation. Participants are randomized into two arms: high-dose (standard care) versus attenuated-dose post-transplant cyclophosphamide (PTCy), both in addition to sirolimus and mycophenolate mofetil (MMF).

Study Record Dates

• First Submitted: January 15, 2025
• First Posted: January 29, 2025
• Study Start: June 23, 2025
• Primary Completion (Estimated): April 1, 2031
• Study Completion (Estimated): November 1, 2031
• Last Updated: December 15, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)