Phase 3
N=151
Chronic Graft-versus-Host Disease Treatment (BMT CTN 0801)
Chronic GVHD
Bottom Line
View on ClinicalTrials.gov: NCT01106833 ↗Enrolled (actual)
151
Serious AEs
18.1%
Results posted
Aug 2018
Primary outcome: Primary: Proportion of Participants With Treatment Success — 33; 35; 33; 37 Participants — p=0.63
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Sirolimus + calcineurin inhibitor + prednisone (Drug); Sirolimus + prednisone (Drug)
- Age
- Pediatric, Adult, Older Adult
- Sex
- All
- Sponsor
- Medical College of Wisconsin
- Primary completion
- Feb 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Proportion of Participants With Treatment Success |
33; 35; 33; 37; 9; 10 | 0.63 |
| SECONDARY Percentage of Participants With Overall Survival |
85.5; 91.7; 74.0; 81.5 | 0.205 |
| SECONDARY Percentage of Participants With Progression-free Survival |
84.0; 90.3; 67.3; 78.6 | 0.141 |
| SECONDARY Percentage of Participants With Failure-free Survival |
74.7; 73.6; 46.2; 48.6 | 0.775 |
| SECONDARY Percentage of Participants With Relapse |
4.8; 1.4; 14.9; 10.1 | 0.396 |
| SECONDARY Percentage of Participants With Secondary Immunosuppressive Therapy Initiated |
12.9; 13.9; 29.4; 38.5 | 0.219 |
| SECONDARY Percentage of Participants With Discontinuation of Systemic Immunosuppressive Therapy at Two Years |
20; 23.2 | 0.706 |
| SECONDARY Prednisone Dose |
0.9; 0.9; 0.2; 0.2; 0.2; 0.1 | 0.127 |
| SECONDARY Change in Prednisone Dose From Baseline |
-0.6; -0.6; -0.6; -0.7 | 0.586 |
| SECONDARY Serum Creatinine Level |
0.9; 0.9; 1.0; 1.0; 0.9; 0.9 | 0.582 |
| SECONDARY Change in Serum Creatinine Level From Baseline |
0.1; 0.1; 0.0; 0.0 | 0.147 |
| SECONDARY Patient-reported Chronic GVHD Severity |
0; 0; 21; 20; 23; 32 | 0.620 |
| SECONDARY Provider-reported Chronic GVHD Severity |
1; 0; 13; 17; 46; 48 | 0.450 |
| SECONDARY NIH Consensus Criteria Chronic GVHD Severity |
0; 1; 1; 1; 29; 23 | 0.238 |
| SECONDARY SF-36 Physical Component Summary |
38; 38; 39; 42; 38; 43 | 0.685 |
| SECONDARY SF-36 Mental Component Summary |
47; 48; 49; 50; 50; 48 | 0.631 |
| SECONDARY FACT-BMT Score |
103; 104; 105; 110; 109; 109 | 0.763 |
Summary
This study is designed as a combined Phase II/III, randomized, open label, multicenter, prospective comparative study of sirolimus plus prednisone versus sirolimus/calcineurin-inhibitor plus prednisone for the treatment of chronic GVHD. Patients will be stratified by transplant center and will be randomized to an experimental arm of one of the two pre-specified experimental arms (sirolimus + prednisone or the comparator arm of sirolimus + calcineurin inhibitor + prednisone) in a 1:1 ratio.
Eligibility Criteria
Inclusion Criteria
- Suitable candidates are patients with classic chronic GVHD or overlap syndrome (classic chronic plus acute GVHD)that is: a)Previously untreated (newly diagnosed) as defined by having received < 14 days of prednisone (or equivalent) before enrollment/randomization to study therapy; b)Previously treated but inadequately responding after ≤ 16 weeks of initial therapy with prednisone and/or calcineurin inhibitor (CNI) ± additional non-sirolimus agent (started at the time of chronic GVHD diagnosis).
- Patient or guardian willing and able to provide informed consent.
- Stated willingness to use contraception in women of childbearing potential.
- Stated willingness of patient to comply with study procedures and reporting requirements.
Exclusion Criteria
- Patients with late persistent acute GVHD or recurrent acute GVHD only.
- Inability to begin prednisone therapy at a dose of greater than 0.5 mg/kg/day.
- Receiving sirolimus for treatment of chronic GVHD (sirolimus for prophylaxis or treatment of acute GVHD is acceptable).
- Already receiving sirolimus (for prophylaxis or treatment of acute GVHD) with prednisone at ≥ 0.25 mg/kg/day (or equivalent) ± additional agents.
- Receiving therapy for chronic GVHD for more than 16 weeks.
- Invasive fungal or viral infection not responding to appropriate antifungal or antiviral therapies.
- Inadequate renal function defined as measured creatinine clearance less than 50 mL/min/1.73 m^2 based on the Cockcroft-Gault formula (adults) or Schwartz formula (age less than or equal to 12 years). Adults: estimated creatinine clearance rate (eCCr) (mL/min/) = (140 - age) x mass (kg) x (0.85 if female)/72 x serum creatinine (mg/dL; Creatinine clearance (mL/min/1.73m^2) = eCCr x 1.73/Body Surface Area (BSA) (m^2); Children: eCCr (mL/min/1.73 m^2) = k x height (cm) / serum creatinine (mg/dL) k = 0.33 (pre-term), 0.45 (full term to 1 year old), 0.55 (age 1-12 years).
- Inability to tolerate oral medications.
- Absolute neutrophil count less than 1500 per microliter.
- Requirement for platelet transfusions.
- Pregnancy (positive serum β-HCG) or breastfeeding.
- Receiving any treatment for persistent, progressive or recurrent malignancy.
- Progressive or recurrent malignancy defined other than by quantitative molecular assays.
- Known hypersensitivity to sirolimus.
Data sourced from ClinicalTrials.gov (NCT01106833). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.