Optimizing GVHD Prophylaxis After Allogeneic Hematopoietic Cell Transplantation

NCT ID: NCT06799195

Last Updated: 2025-12-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

126 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-06-23

Study Completion Date

2031-11-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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).

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Hematological Malignancies Graft-versus-Host Disease (GVHD)

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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).
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Not applicable; the study is open-label.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Attenuated-dose post-transplant cyclophosphamide (PTCy) Arm

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.

Group Type EXPERIMENTAL

Attenuated-dose Cyclophosphamide

Intervention Type DRUG

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

Sirolimus

Intervention Type 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)

Intervention Type 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.

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

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.

Group Type ACTIVE_COMPARATOR

High-dose Cyclophosphamide

Intervention Type DRUG

Cyclophosphamide administered at the standard high dose of 50 mg/kg on days +3 and +4 post-transplant for GVHD prophylaxis.

Sirolimus

Intervention Type 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)

Intervention Type 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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Attenuated-dose Cyclophosphamide

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

Intervention Type DRUG

High-dose Cyclophosphamide

Cyclophosphamide administered at the standard high dose of 50 mg/kg on days +3 and +4 post-transplant for GVHD prophylaxis.

Intervention Type DRUG

Sirolimus

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.

Intervention Type DRUG

Mycophenolate 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.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University of Nebraska

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Moataz Ellithi, MBChB

Role: PRINCIPAL_INVESTIGATOR

University of Nebraska

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United States

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Taylor Johnson

Role: CONTACT

402-559-4596

IIT OFFICE

Role: CONTACT

402-559-4596

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Taylor Johnson

Role: primary

402-559-4596

A

Role: backup

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 34855460 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 363972 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21464398 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9051246 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

0094-25-FB

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.