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Chronic GVHD | Chronic Graft-versus-Host Disease Treatment (BMT CTN 0801)

Chronic GVHD research study

What is the primary objective of this study?

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.

Who is eligible to participate?

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.

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Chronic GVHD

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Drug:Sirolimus + calcineurin inhibitor + prednisoneThe 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.

Drug:Sirolimus + prednisoneThe 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.

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

calcineurin inhibitorSirolimus + calcineurin inhibitor + prednisone

Sirolimus and prednisoneSirolimus + prednisone

Study Status

Completed

Start Date: April 2010

Completed Date: June 2018

Phase: Phase 2/Phase 3

Type: Interventional

Design:

Primary Outcome: Proportion of Participants With Treatment Success

Secondary Outcome: Percentage of Participants With Overall Survival

Study sponsors, principal investigator, and references

Principal Investigator: Mary Horowitz, MD

Lead Sponsor: Medical College of Wisconsin

Collaborator: National Heart, Lung, and Blood Institute (NHLBI)

More information:https://clinicaltrials.gov/show/NCT01106833

Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005 Dec;11(12):945-56.

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