Chronic Graft-versus-Host Disease Treatment (BMT CTN 0801)
- Conditions
- Chronic GVHD
- Interventions
- Registration Number
- NCT01106833
- Lead Sponsor
- Medical College of Wisconsin
- Brief 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.
- Detailed 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 151
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description calcineurin inhibitor Sirolimus + calcineurin inhibitor + prednisone Sirolimus + calcineurin inhibitor + prednisone Sirolimus and prednisone Sirolimus + prednisone Sirolimus + prednisone
- Primary Outcome Measures
Name Time Method Proportion of Participants With Treatment Success 6 months and 24 months post-randomization Treatment success was evaluated at 6 months in Phase II and is defined as a complete or partial response without secondary systemic immunosuppressive therapy and no recurrent malignancy or death. In Phase III, treatment success was evaluated at 24 months and is defined as a complete response without secondary systemic immunosuppressive therapy and no recurrent malignancy or death.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Overall Survival 6 months and 24 months post-randomization Overall survival is defined as survival of death from any cause.
Percentage of Participants With Progression-free Survival 6 months and 24 months post-randomization Progression-free Survival is defined as survival without malignancy relapse. Relapse and death are considered failures for this endpoint.
Percentage of Participants With Failure-free Survival 6 months and 24 months post-randomization Failure-free Survival is defined as survival without malignancy progression or initiation of secondary therapy for chronic GVHD. Progression, initiation of secondary therapy for chronic GVHD, and death are considered failures for this endpoint.
Percentage of Participants With Relapse 6 months and 24 months post-randomization Relapse is defined as recurrence of the primary malignancy. Death is considered a competing risk for this endpoint.
Percentage of Participants With Secondary Immunosuppressive Therapy Initiated 6 months and 24 months post-randomization The percentage of participants initiating secondary immunosuppressive therapy for chronic GVHD is described. Death is considered a competing risk for this endpoint.
Percentage of Participants With Discontinuation of Systemic Immunosuppressive Therapy at Two Years 2 years post-randomization The percentage of participants discontinuing all systemic immunosuppressive therapy by two years post-randomization is described. Death is considered a competing risk for this endpoint.
Prednisone Dose Baseline, 6 months, and 1 year post-randomization Daily dose of prednisone is described by treatment arm at baseline, 6 months, and 1 year post-randomization.
Change in Serum Creatinine Level From Baseline 6 months and 1 year post-randomization Change in creatinine level from baseline, the time of randomization, is described by treatment arm at 6 months and 1 year post-randomization.
Patient-reported Chronic GVHD Severity Baseline, 6 months, 1 year, and 2 years post-randomization Each patient's perception of the severity of the chronic GVHD was collected at baseline and at 6 months, 1 year, and 2 years post-randomization. Severity is categorized as none, mild, moderate, and severe.
Provider-reported Chronic GVHD Severity Baseline, 6 months, 1 year, and 2 years post-randomization Each patient's care provider's perception of the severity of the chronic GVHD was collected at baseline and at 6 months, 1 year, and 2 years post-randomization. Severity is categorized as none, mild, moderate, and severe.
Change in Prednisone Dose From Baseline 6 months and 1 year post-randomization Change in the daily dose of prednisone from baseline, the time of randomization, is described by treatment arm at 6 months and 1 year post-randomization.
Serum Creatinine Level Baseline, 6 months, and 1 year post-randomization Creatinine level is described by treatment arm at baseline, 6 months, and 1 year post-randomization.
SF-36 Physical Component Summary Baseline, 2 months, 6 months, 1 year, and 2 years post-randomization The Medical Outcome Study SF-36 Physical Component Summary (PCS) is a subscale of the SF-36 intended to measure physical well-being. It is scored on a scale of 0-100, with higher scores indicating higher levels of well-being.
FACT-BMT Score Baseline, 2 months, 6 months, 1 year, and 2 years post-randomization The Functional Assessment of Cancer Therapy-Bone Marrow Transplant scale (FACT-BMT) is a quality of life instrument that assesses the effects of bone marrow transplantation (BMT) on a patient's physical, social/family, emotional, and functional well-being while taking into consideration BMT-specific concerns. The assessment has 37 questions, each scored on a Likert scale from 0-4. The overall score is computed by adding scores of the questions and falls in the range 0-148, with higher scores indicating higher levels of overall well-being.
SF-36 Mental Component Summary Baseline, 2 months, 6 months, 1 year, and 2 years post-randomization The Medical Outcome Study SF-36 Mental Component Summary (MCS) is a subscale of the SF-36 intended to measure mental well-being. It is scored on a scale of 0-100, with higher scores indicating higher levels of well-being.
NIH Consensus Criteria Chronic GVHD Severity Baseline, 6 months, 1 year, and 2 years post-randomization Chronic GVHD severity was determined at baseline and at 6 months, 1 year, and 2 years post-randomization per the 2005 NIH Consensus Criteria (Filipovich et al. 2005). Severity is categorized as none, mild, moderate, and severe.
Trial Locations
- Locations (31)
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
City of Hope National Medical Center
🇺🇸Duarte, California, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Blood & Marrow Transplant Program at Northside Hospital
🇺🇸Atlanta, Georgia, United States
University of Kansas Hospital
🇺🇸Kansas City, Kansas, United States
Stanford Hospital and Clinics
🇺🇸Stanford, California, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Washington University, Barnes Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
University of California San Diego Medical Center
🇺🇸La Jolla, California, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
University of Pennsylvania Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Western Pennsylvania Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
University of Florida College of Medicine (Shands)
🇺🇸Gainesville, Florida, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
University of Michigan Medical Center
🇺🇸Ann Arbor, Michigan, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Mayo Clinic
🇺🇸Rochester, New York, United States
University of North Carolina Hospital at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Jewish Hospital BMT Program
🇺🇸Cincinnati, Ohio, United States
University of Oklahoma Medical Center
🇺🇸Oklahoma City, Oklahoma, United States
Oregon Health & Science University (A) and (P)
🇺🇸Portland, Oregon, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
University of Texas/MD Anderson CRC
🇺🇸Houston, Texas, United States
University Hospitals of Cleveland/ Case Western
🇺🇸Cleveland, Ohio, United States
Texas Transplant Institute
🇺🇸San Antonio, Texas, United States
Virginia Commonwealth University/MCV Hospitals
🇺🇸Richmond, Virginia, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
University of Wisconsin Hospital and Clinics
🇺🇸Madison, Wisconsin, United States