Allogeneic HSCT With Low-Dose Post-Transplant Cyclophosphamide for GVHD Prevention

NCT06926595 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: PSCI-24-047
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase 2, single-arm, open-label study aims to evaluate the safety and efficacy of low-dose (25 mg/kg) post-transplant cyclophosphamide (PTCy) for prophylaxis of Graft-versus-Host Disease (GVHD) in patients undergoing allogeneic stem cell transplantation following reduced-intensity or non-myeloablative conditioning. The study will focus on matched sibling, matched unrelated, and haploidentical peripheral blood stem cell donors. The primary endpoint is 1-year GVHD-Free Relapse-Free Survival (GRFS). The study seeks to determine if low-dose PTCy offers similar outcomes as higher doses, with potentially reduced toxicity.

Conditions

Graft-versus-Host Disease (GVHD); Hematologic Malignancies; Allogeneic Stem Cell Transplantation

Outcome Measures

Primary Outcomes (3)

• Number of Subjects Without Grade III/IV Acute Graft-Versus-Host Disease (GVHD) at 1 Year

  The number of subjects without Grade III/IV acute graft-versus-host disease (GVHD) at one year following allogeneic stem cell transplantation, assessed using the Modified Glucksberg Criteria (Grade III: severe organ involvement, e.g., skin stage 3-4, liver or gut stage 2-3; Grade IV: life-threatening dysfunction, e.g., skin, liver, or gut stage 4).

  1 year post-transplant

• Number of Subjects Without Chronic Graft-Versus-Host Disease (GVHD) Requiring Systemic Treatment at 1 Year

  The number of subjects without chronic graft-versus-host disease (GVHD) requiring systemic treatment (e.g., corticosteroids or immunosuppressive therapy) at one year following allogeneic stem cell transplantation with low-dose post-transplant cyclophosphamide (25 mg/kg), assessed per the NIH Consensus Criteria for chronic GVHD.

  1 year post-transplant

• Number of Subjects Without Relapse or Disease Progression at 1 Year

  The number of subjects without relapse or disease progression at one year following allogeneic stem cell transplantation, defined as the reappearance of the underlying disease or worsening of disease burden, assessed by standard clinical and laboratory measures (e.g., bone marrow biopsy, or disease-specific markers such as minimal residual disease \[MRD\] testing) per the study protocol.

  1 year post-transplant

Study Arms (1)

Low-Dose PTCy for GVHD Prophylaxis

EXPERIMENTAL

Participants in this single-arm study will receive low-dose (25 mg/kg) post-transplant cyclophosphamide (PTCy) on days +3 and +4 following allogeneic hematopoietic stem cell transplantation. This will be administered in combination with tacrolimus and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis. The study includes patients receiving transplants from matched sibling, matched unrelated, single allelic mismatched unrelated, and haploidentical donors following reduced-intensity or non-myeloablative conditioning.

Drug: Cyclophosphamide (primary intervention for GVHD prophylaxis)

Interventions

Cyclophosphamide (primary intervention for GVHD prophylaxis) DRUG

This study evaluates the use of low-dose (25 mg/kg) post-transplant cyclophosphamide (PTCy) for prophylaxis of Graft-versus-Host Disease (GVHD) following allogeneic stem cell transplantation. The intervention involves administering PTCy on days +3 and +4 post-transplant, in combination with tacrolimus and mycophenolate mofetil (MMF) for GVHD prevention. The goal is to assess the safety and efficacy of this regimen in patients undergoing reduced-intensity or non-myeloablative conditioning using peripheral blood stem cells from matched sibling, matched unrelated, and haploidentical donors

Also known as: Tacrolimus (part of the GVHD prophylaxis regimen), Mycophenolate mofetil (MMF) (part of the GVHD prophylaxis regimen)

Low-Dose PTCy for GVHD Prophylaxis

Eligibility Criteria

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

You may qualify if:

• Age 18 or older at the time of study enrollment.
• Patients with acute leukemia (acute myeloid leukemia, acute lymphoblastic leukemia, mixed phenotype acute leukemia) or chronic myeloid leukemia with no circulating blasts and less than 5% blasts in the bone marrow.
• Flow cytometric, polymerase chain reaction (PCR) or next generation sequencing (NGS) detected measurable residual disease is permitted.
• Patients with myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia with no circulating blasts and less than 10% blasts in the bone marrow (exception allowed due to lack of difference in outcomes with \<5% vs 5-10% blasts in this disease).
• Patients with secondary acute myeloid leukemia progressing from pre-existing myelodysplastic syndrome, myeloproliferative disease (MPN), or MDS/MPN overlap syndrome.
• Patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma who are indicated for allogeneic stem cell transplantation.
• Patients with lymphoma who are indicated for allogeneic stem cell transplantation, including follicular lymphoma, Hodgkin lymphoma, diffuse large B cell lymphoma (including primary mediastinal B cell lymphoma), mantle cell lymphoma, peripheral T cell lymphomas, and Richter's transformation.
• Planned reduced intensity or non-myeloablative conditioning regimen.
• Patients must have a related or unrelated peripheral blood stem cell donor as follows:
• Sibling donor must be at least haploidentical using high resolution DNA-based HLA typing.
• Children or parent donor must be at least haploidentical using high resolution DNA-based HLA typing. Children donors must be at least 18 years of age at the time of evaluation.
• Unrelated donors must be a 7/8 or 8/8 match at HLA-A, B, C, and DRB1 at high resolution using DNA based typing.
• Cardiac function: must demonstrate at ejection fraction of at least 40%.
• Pulmonary function: must have FEV1 of at least 50% predicted, and DLCO corrected for hemoglobin of at least 40% predicted.
• Karnofsky performance status at least 70%.

You may not qualify if:

• Prior allogeneic stem cell transplant.
• Active central nervous system (CNS) involvement by malignant cells.
• Uncontrolled bacterial, viral, or fungal infections (currently taking medication with progression or no clinical improvement).
• Seropositive for human immunodeficiency virus (HIV) with detectable viral load, hepatitis B virus (HBV) or hepatitis C virus (HCV) with detectable viral load. Hepatitis B surface antibody positive due to vaccination or natural immunity are permitted. Patients previously treated for HCV and considered to be in sustained virologic remission (SVR) are allowed.
• Myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) class III-IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia.
• Pregnant or lactating female patients (unless feeding via formula). Women of childbearing potential (WOCBP) are required to have a negative serum or urine pregnancy test prior to conditioning regimen.
• Serious medical or psychiatric illness likely to interfere with participation in the study.
• Use of investigational agents.
• Haploidentical related recipient who are positive for DSA ≥ 5000 MFI by solid phase microarray method (Luminex).
• Any patient with steroid dose more than 10 mg/day within a week of registration.
• Autoimmune disorder requiring any active immunosuppression therapy.

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead

Study Sites (1)

Penn State Cancer Institute

Hershey, Pennsylvania, 17033, United States

Location

MeSH Terms

Conditions

Graft vs Host Disease; Hematologic Neoplasms

Interventions

Cyclophosphamide; Tacrolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

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

• Joseph Cioccio, MD

  Penn State Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Crystal Sowers

CONTACT

7175315471; psci-cto@pennstatehealth.psu.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Model Details: This is a single-arm, open-label, Phase 2 clinical trial. All participants will receive the same intervention, which is low-dose (25 mg/kg) post-transplant cyclophosphamide (PTCy) for GVHD prophylaxis, in combination with tacrolimus and mycophenolate mofetil (MMF). The study will assess the safety and efficacy of this regimen in patients undergoing allogeneic stem cell transplantation using peripheral blood stem cells from matched sibling, matched unrelated, and haploidentical donors, following reduced-intensity or non-myeloablative conditioning.

Study Record Dates

• First Submitted: April 10, 2025
• First Posted: April 13, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): October 1, 2030
• Study Completion (Estimated): October 1, 2031
• Last Updated: December 3, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)