Overview

This trial is active, not recruiting.

Condition chronic gvhd
Treatments sirolimus + calcineurin inhibitor + prednisone, sirolimus + prednisone
Phase phase 2/phase 3
Targets mTOR, FKBP-12
Sponsor Medical College of Wisconsin
Collaborator National Heart, Lung, and Blood Institute (NHLBI)
Start date April 2010
End date March 2019
Trial size 161 participants
Trial identifier NCT01106833, BMT CTN 0801, BMTCTN0801, U01HL069294, U01HL06929406

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
Sirolimus + calcineurin inhibitor + prednisone
sirolimus + calcineurin inhibitor + prednisone Rapamune
The target serum level for sirolimus is 3-12 ng/mL. The target serum level for tacrolimus is 5-10 ng/mL. The target serum level for cyclosporine is 120-200 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.
(Experimental)
Sirolimus + prednisone
sirolimus + prednisone Rapamune
The target serum level for sirolimus is 3-12 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.

Primary Outcomes

Measure
Phase II: Proportion of subjects with Complete Response or Partial Response; Phase III: Proportion of subjects with Complete Response; resolution of graft versus host disease manifestations
time frame: Phase II: 6 months; Phase III: 24 months

Secondary Outcomes

Measure
Phase II: Avg. daily dose % reduction of prednisone
time frame: 6 and 12 months
Phase II: Cumulative incidence of treatment failure
time frame: 1 year
Phase II: Prevalence of active symptomatic chronic GVHD
time frame: 1 and 2 years
Phase II: Incidence of discontinuation of all systemic immunosuppressive therapy
time frame: 1 and 2 years
Phase II: Overall and cancer progression-free survival
time frame: 1 and 2 years
Phase II: Serum biomarkers of chronic GVHD
time frame: baseline, 2 and 6 months
Phase III: Avg. daily dose % reduction of prednisone
time frame: 6, 12 and 24 months
Phase III: Cumulative incidence of treatment failure
time frame: 1 and 2 years
Phase III: Prevalence of active symptomatic chronic GVHD
time frame: 1 and 2 years
Phase III: Incidence of discontinuation of all systemic immunosuppressive therapy
time frame: 1 and 2 years
Phases III: Overall and cancer progression-free survival
time frame: 1 and 2 years
Phase III: Serum biomarkers of chronic GVHD
time frame: baseline, 1 and 2 years

Eligibility Criteria

Male or female participants of any age.

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.

Additional Information

Official title A Phase II/III Randomized, Multicenter Trial Comparing Sirolimus Plus Prednisone and Sirolimus/Calcineurin Inhibitor Plus Prednisone for the Treatment of Chronic Graft-versus-Host Disease (BMT CTN Protocol #0801)
Description Background: Chronic GVHD is a medical condition that can become very serious. Chronic GVHD is a common development after allogeneic transplant that occurs when the donor cells attack and damage tissues. The primary purpose of this study is to compare treatment regimens that contain sirolimus without a calcineurin inhibitor to a comparator regimen of sirolimus with a calcineurin inhibitor and evaluate how well chronic GVHD responds to treatment. The combinations of medications in this study are: - Sirolimus + calcineurin inhibitor + prednisone - Sirolimus + prednisone The goal is to select a treatment regimen for further comparison in the Phase III trial. Design Narrative: The intent is to enroll subjects at the start of initial therapy for chronic GVHD, or before their chronic GVHD is refractory to glucocorticoid therapy, or is chronically dependent upon glucocorticoid therapy and multiple secondary systemic immunosuppressive agents. Patients will be stratified by transplant center and will be randomized to one of two arms.
Trial information was received from ClinicalTrials.gov and was last updated in January 2016.
Information provided to ClinicalTrials.gov by Medical College of Wisconsin.
Location data was received from the National Cancer Institute and was last updated in August 2016.