A Study to Evaluate Steroid-free Treatment for Standard-Risk aGVHD (BMT CTN 1501)


About this study

The study is a Phase II randomized, open label, multicenter trial designed to identify whether sirolimus is a potential alternative to prednisone as an up-front treatment for patients with standard-risk acute GVHD defined according to clinical and biomarker-based risk stratification. This trial incorporates both a novel up front GVHD therapy (sirolimus) as well as a novel BMT CTN developed acute GVHD biomarker test.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  1. Patients with standard-risk acute GVHD, according to refined Minnesota Criteria. Refined Minnesota Criteria are available at https://redcap.ahc.umn.edu/surveys/?s=bNmFhseJIf. Standard-risk acute GVHD according to the refined Minnesota Risk Criteria requires meeting one of the criteria below:
    1. Single organ involvement (Stage 1-3 skin, Stage 1 upper GI, or Stage 1-2 lower GI)
    2. Multiple organ involvement (Stage 1-3 skin plus stage 1 upper GI, Stage 1-3 skin plus stage 1 lower GI, Stage 1-3 skin plus stage 1 lower GI plus stage 1 upper GI, Stage 1-3 skin plus stage 1-4 liver, or Stage 1 lower GI plus stage 1 upper GI)
  2. Acute Minnesota Standard Risk GVHD requiring systemic immune suppressive therapy.
  3. Acute GVHD developing after allogeneic hematopoietic cell transplantation using either bone marrow, peripheral blood, or umbilical cord blood. Recipients of non-myeloablative, reduced intensity conditioning and myeloablative transplants are eligible. All allogeneic donor sources are permitted, including siblings, unrelated donors, human leukocyte antigen (HLA)-haploidentical related donors and umbilical cord blood.
  4. Patients NOT receiving systemic immune suppressive therapy for treatment of active GVHD (topical skin and GI corticosteroids are allowed).
  5. Ability to tolerate oral or enterically-administered medications.
  6. Patients of all ages.
  7. Absolute neutrophil count (ANC) greater than 500/µL.
  8. Biopsy confirmation of GVHD is not required. Enrollment should not be delayed for biopsy or pathology results unless local institutional practice mandates biopsy confirmation to make a GVHD treatment decision.
  9. Written informed consent and/or assent from patient, parent or guardian.
  10. Collection of a 5 ml blood sample (red top for serum) from the patient for Ann Arbor Scoring and ready to be shipped immediately after randomization.

Exclusion Criteria:

  1. Patients receiving sirolimus (for any indication including GVHD prophylaxis) within 14 days of screening for enrollment.
  2. Relapsed, progressing or persistent malignancy requiring withdrawal of systemic immune suppression.
  3. Patients with acute GVHD developing after a donor lymphocyte infusion.
  4. Active or recent (within 7 days) episode of transplant associated microangiopathy.
  5. Patients with uncontrolled infections will be excluded. Infections are considered controlled if appropriate therapy has been instituted and, at the time of enrollment, no signs of progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
  6. Patients unlikely to be available for evaluation at the transplant center on Day 28 and 56 of therapy.
  7. A clinical presentation resembling de novo chronic GVHD or overlap syndrome developing before or present at the time of enrollment.
  8. Patients receiving corticosteroids for any indication within 7 days before the onset of acute GVHD, except the following: Stable replacement doses of corticosteroids for adrenal insufficiency are permitted (e.g. hydrocortisone total dose of 10-12 mg/m^2/day or prednisone 5-7.5mg daily or equivalent). Corticosteroids administered as premedication before transfusion of blood products or before intravenous medications to prevent infusion reactions are allowed.
  9. Patients who are pregnant or breastfeeding.
  10. Females of childbearing potential (FCBP) or a man who has sexual contact with a FCBP and is unwilling to use effective birth control for the duration of the study.
  11. Patients on dialysis.
  12. Patients on mechanical ventilation.
  13. Patients with severe hepatic sinusoidal obstruction syndrome who in the judgment of the treating physician are not expected to have normalized bilirubin by Day 56 after enrollment.
  14. Patients with a history of hypersensitivity to sirolimus or any component of the formulation.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Rochester, Minn.

Mayo Clinic principal investigator

William Hogan, M.B., B.Ch.

Closed for enrollment

More information


  • This consensus document is intended to serve 3 functions. First, it standardizes the criteria for diagnosis of chronic graft-versus-host disease (GVHD). Second, it proposes a new clinical scoring system (0-3) that describes the extent and severity of chronic GVHD for each organ or site at any given time, taking functional impact into account. Third, it proposes new guidelines for global assessment of chronic GVHD severity that are based on the number of organs or sites involved and the degree of involvement in affected organs (mild, moderate, or severe). Diagnosis of chronic GVHD requires the presence of at least 1 diagnostic clinical sign of chronic GVHD (e.g., poikiloderma or esophageal web) or the presence of at least 1 distinctive manifestation (e.g., keratoconjunctivitis sicca) confirmed by pertinent biopsy or other relevant tests (e.g., Schirmer test) in the same or another organ. Furthermore, other possible diagnoses for clinical symptoms must be excluded. No time limit is set for the diagnosis of chronic GVHD. The Working Group recognized 2 main categories of GVHD, each with 2 subcategories. The acute GVHD category is defined in the absence of diagnostic or distinctive features of chronic GVHD and includes (1) classic acute GVHD occurring within 100 days after transplantation and (2) persistent, recurrent, or late acute GVHD (features of acute GVHD occurring beyond 100 days, often during withdrawal of immune suppression). The broad category of chronic GVHD includes (1) classic chronic GVHD (without features or characteristics of acute GVHD) and (2) an overlap syndrome in which diagnostic or distinctive features of chronic GVHD and acute GVHD appear together. It is currently recommended that systemic therapy be considered for patients who meet criteria for chronic GVHD of moderate to severe global severity. Read More on PubMed

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