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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Blood and Marrow Transplant Clinical Trials Network
Information provided by (Responsible Party):
Medical College of Wisconsin
ClinicalTrials.gov Identifier:
NCT01106833
First received: April 16, 2010
Last updated: November 21, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention Phase
Chronic GVHD
Drug: Sirolimus + calcineurin inhibitor + prednisone
Drug: Sirolimus + prednisone
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Medical College of Wisconsin:

Primary Outcome Measures:
  • Phase II: Proportion of subjects with Complete Response or Partial Response [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Phase III: Proportion of subjects with Complete Response; resolution of graft versus host disease manifestations [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Phase II: Avg. daily dose % reduction of prednisone [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
  • Phase II: Cumulative incidence of treatment failure [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Phase II: Prevalence of active symptomatic chronic GVHD [ Time Frame: 1 and 2 years ] [ Designated as safety issue: No ]
  • Phase II: Incidence of discontinuation of all systemic immunosuppressive therapy [ Time Frame: 1 and 2 years ] [ Designated as safety issue: No ]
  • Phase II: Overall and cancer progression-free survival [ Time Frame: 1 and 2 years ] [ Designated as safety issue: No ]
  • Phase II: Serum biomarkers of chronic GVHD [ Time Frame: baseline, 2 and 6 months ] [ Designated as safety issue: No ]
  • Phase III: Avg. daily dose % reduction of prednisone [ Time Frame: 6, 12 and 24 months ] [ Designated as safety issue: No ]
  • Phase III: Cumulative incidence of treatment failure [ Time Frame: 1 and 2 years ] [ Designated as safety issue: No ]
  • Phase III: Prevalence of active symptomatic chronic GVHD [ Time Frame: 1 and 2 years ] [ Designated as safety issue: No ]
  • Phase III: Incidence of discontinuation of all systemic immunosuppressive therapy [ Time Frame: 1 and 2 years ] [ Designated as safety issue: No ]
  • Phases III: Overall and cancer progression-free survival [ Time Frame: 1 and 2 years ] [ Designated as safety issue: No ]
  • Phase III: Serum biomarkers of chronic GVHD [ Time Frame: baseline, 1 and 2 years ] [ Designated as safety issue: No ]

Enrollment: 161
Study Start Date: April 2010
Estimated Study Completion Date: March 2019
Estimated Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Sirolimus + calcineurin inhibitor + prednisone
Sirolimus + calcineurin inhibitor + prednisone
Drug: Sirolimus + calcineurin inhibitor + prednisone

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.

Other Names:
  • Rapamune
  • Prograf
  • Neorall
  • Gengraf
Experimental: Sirolimus + prednisone
Sirolimus + prednisone
Drug: Sirolimus + prednisone

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.

Other Name: Rapamune

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01106833

  Hide Study Locations
Locations
United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010-3000
University of California San Diego Medical Center
La Jolla, California, United States, 92093
Stanford Hospital and Clinics
Stanford, California, United States, 94305
United States, Florida
University of Florida College of Medicine (Shands)
Gainesville, Florida, United States, 32610-0277
United States, Georgia
Blood & Marrow Transplant Program at Northside Hospital
Atlanta, Georgia, United States, 30342
Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637-1470
United States, Kansas
University of Kansas Hospital
Kansas City, Kansas, United States, 66160
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21231
United States, Michigan
University of Michigan Medical Center
Ann Arbor, Michigan, United States, 48105-2967
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Washington University, Barnes Jewish Hospital
St. Louis, Missouri, United States, 63110
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-7680
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10174
Mayo Clinic
Rochester, New York, United States, 55905
United States, North Carolina
University of North Carolina Hospital at Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7305
Duke University Medical Center
Durham, North Carolina, United States, 27705
United States, Ohio
Jewish Hospital BMT Program
Cincinnati, Ohio, United States, 45236
University Hospitals of Cleveland/ Case Western
Cleveland, Ohio, United States, 44106-5061
United States, Oklahoma
University of Oklahoma Medical Center
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
Oregon Health & Science University (A) and (P)
Portland, Oregon, United States, 97239-3098
United States, Pennsylvania
University of Pennsylvania Cancer Center
Philadelphia, Pennsylvania, United States, 19104
Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, United States, 15224
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Texas
University of Texas/MD Anderson CRC
Houston, Texas, United States, 77030
Texas Transplant Institute
San Antonio, Texas, United States, 78229
United States, Virginia
Virginia Commonwealth University/MCV Hospitals
Richmond, Virginia, United States, 23298
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
United States, West Virginia
West Virginia University Hospital
Morgantown, West Virginia, United States, 26506-9162
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792-5156
Sponsors and Collaborators
Medical College of Wisconsin
Blood and Marrow Transplant Clinical Trials Network
Investigators
Study Chair: Paul Carpenter, MB, BS Fred Hutchinson Cancer Research Center
Study Chair: Mukta Arora, MD University of Minnesota - Clinical and Translational Science Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT01106833     History of Changes
Other Study ID Numbers: 609, U01HL069294, BMT CTN 0801, U01HL069294-06
Study First Received: April 16, 2010
Last Updated: November 21, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Medical College of Wisconsin:
Chronic Graft-versus-Host Disease (cGVHD)

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Everolimus
Prednisone
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014