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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by Medical College of Wisconsin
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: May 29, 2013
Last verified: May 2013
  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 #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 CR/PR [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Phase III: Proportion of subjects with CR; resolution of GVHD 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 ]

Estimated Enrollment: 300
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 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 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 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: 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/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

Contacts
Contact: Mary Horowitz, MD, MS marymh@mcw.edu

  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham Not yet recruiting
Birmingham, Alabama, United States, 35294
United States, Arizona
Arizona Canter Center, University of Arizona Recruiting
Tucson, Arizona, United States, 85724-5024
Contact: Emmanuel Katsanis, MD    520-626-4851    ekatsani@email.arizona.edu   
Contact: Andrew Yeager, MD    520-626-3191    ayeager@azcc.arizona.edu   
United States, California
City of Hope National Medical Center Recruiting
Duarte, California, United States, 91010-3000
Contact: Stephen Forman, MD    626-359-8111    sforman@coh.org   
Contact: Pablo Parker, MD       pparker@coh.org   
University of California San Diego Medical Center Recruiting
La Jolla, California, United States, 92093
Contact: Edward Ball, MD    858-822-6380    tball@ucsd.edu   
Stanford Hospital and Clinics Recruiting
Stanford, California, United States, 94305
Contact: Laura Johnston, MD    650-723-0822    korb@stanford.edu   
United States, Florida
University of Florida College of Medicine (Shands) Recruiting
Gainesville, Florida, United States, 32610-0277
Contact: John Wingard, MD`    352-846-1846    wingajr@medicine.ufl.edu   
All Children's Hospital Recruiting
St. Petersburg, Florida, United States, 33701
Contact: Aleksandra Petrovic, MD    727-767-6856    Aleksandra.petrovic@allkids.org   
United States, Georgia
Children's Healthcare of Atlanta Recruiting
Atlanta, Georgia, United States, 30322-1062
Contact: Ann E Haight, MD    404-785-1191    ann.haight@choa.org   
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Edmund Waller, MD, PhD    404-727-4995    ewaller@emory.edu   
Blood & Marrow Transplant Program at Northside Hospital Recruiting
Atlanta, Georgia, United States, 30342
Contact: Scott Solomon, MD    404-255-1930    ssolomon@bmtga.com   
United States, Illinois
Rush University Medical Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Elizabeth Rich, MD, PhD    312-563-3461    elizabeth_rich@rush.edu   
University of Chicago Recruiting
Chicago, Illinois, United States, 60637-1470
Contact: Andrew Artz, MD, MS    773-834-8980    aartz@medicine.bsd.uchicago.edu   
United States, Indiana
Indiana University Medical Center/Riley Hospital Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Paul Haut, MD       phaut@iupui.edu   
United States, Iowa
University of Iowa Hospitals and Clinics Withdrawn
Iowa City, Iowa, United States, 52242-1009
United States, Kansas
University of Kansas Hospital Recruiting
Kansas City, Kansas, United States, 66160
Contact: Sunil Abhyankar, MD    913-588-6077    sabhyankar@kumc.edu   
United States, Kentucky
University of Louisville/Kosair Children's Hospital Not yet recruiting
Louisville, Kentucky, United States, 40202
Contact: Alexandra Cheerva, MD    502-852-8450    acchee01@louisville.edu   
United States, Maryland
Johns Hopkins University Recruiting
Baltimore, Maryland, United States, 21231
Contact: Javier Bolanos-Meade, MD    410-614-0738    fbolanos2@jhmi.edu   
University of Maryland, Greenbaum Cancer Center Recruiting
Baltimore, Maryland, United States, 21201
Contact: Saul Yanovich, MD    410-328-1230    syanovich@umm.edu   
United States, Massachusetts
Beth Israel Deaconess Medical Center Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Jacalyn Rosenblatt, MD    617-667-9148    jrosenb1@bidmc.harvard.edu   
DFCI/Brigham & Women's Withdrawn
Boston, Massachusetts, United States, 02115
University of Massachusetts/Memorial Medical Center Recruiting
Worcester, Massachusetts, United States, 01655
Contact: Muthalagu Ramanathan, MD       Muthalagu.Ramanathan@umassmemorial.org   
Contact: Lindsey Shanahan, PAC       Lindsey.Shanahan@umassmemorial.org   
United States, Michigan
University of Michigan Medical Center Recruiting
Ann Arbor, Michigan, United States, 48105-2967
Contact: Carrie Kitko, MD    734-936-5406    ckitko@med.umich.edu   
Karmanos Cancer Institute/Children's Hospital of Michigan Recruiting
Detroit, Michigan, United States, 48201
Contact: Sureyya Savasan, MD    313-745-5515    ssavasan@med.wayne.edu   
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Mukta Arora, MD       Arora005@umn.edu   
United States, Missouri
St. Louis Children's Hospital, Washington University Recruiting
St. Louis, Missouri, United States, 63110
Contact: Shalini Shenoy, MD    314-454-6018    shenoy@wustl.edu   
Washington University, Barnes Jewish Hospital Recruiting
St. Louis, Missouri, United States, 63110
Contact: Peter Westervelt, MD, PhD       pwesterv@DOM.wustl.edu   
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198-7680
Contact: Edward Farber Jr., DO, MS    402-559-5520    efaber@unmc.edu   
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Scott Rowley, MD    201-996-3925    srowley@humed.com   
Contact: Alfred Gillo, MD    201-996-5600    agillio@humed.com   
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: George Chen, MD       george.chen@roswellpark.org   
Cohen (Schneider) Children's Hospital Not yet recruiting
New Hyde Park, New York, United States, 11040
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10174
Contact: Jenna Goldberg, M.D.       goldbej2@mskcc.org   
Mount Sinai Medical Center Withdrawn
New York, New York, United States, 10029
Mayo Clinic Recruiting
Rochester, New York, United States, 55905
Contact: Mark Litzow, MD    507-284-5362    litzow.mark@mayo.edu   
United States, North Carolina
University of North Carolina Hospital at Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599-7305
Contact: Thomas Shea, MD    919-966-7746    sheat@med.unc.edu   
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27705
Contact: Suhag Parikh, MD    919-668-1100    suhag.parikh@duke.edu   
Contact: Mitchell Horwitz, MD    919-668-1045    horwi001@mc.duke.edu   
Wake Forest University Health Sciences Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: David Hurd, MD    336-716-2843    dhurd@wfubmc.edu   
United States, Ohio
Jewish Hospital BMT Program Recruiting
Cincinnati, Ohio, United States, 45236
Contact: James Essell, MD    513-686-3420    jessell@ohcmail.com   
University Hospitals of Cleveland/ Case Western Recruiting
Cleveland, Ohio, United States, 44106-5061
Contact: Hillard Lazarus, MD    216-844-3629    hillard.lazarus@case.edu   
United States, Oklahoma
University of Oklahoma Medical Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: George Selby, MD    405-271-6369    George-selby@ouhsc.edu   
United States, Oregon
Oregon Health & Science University (A) and (P) Recruiting
Portland, Oregon, United States, 97239-3098
Contact: Eneida Nemecek, MD       nemeceke@ohsu.edu   
Principal Investigator: Richard Maziarz, MD         
Principal Investigator: Gabrielle Meyers, MD         
United States, Pennsylvania
Fox Chase, Temple University BMT Program Withdrawn
Philadelphia, Pennsylvania, United States, 19111-2442
University of Pennsylvania Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: David Porter, MD    215-662-2867    David.porter@uphs.upenn.edu   
Western Pennsylvania Hospital Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Entezam Sahovic, MD       esahovic@wpahs.org   
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Luciano JM Costa, MD, PhD    843-792-4271    costalj@musc.edu   
United States, Texas
Cook Children's Medical Center Recruiting
Fort Worth, Texas, United States, 76104
Contact: Gretchen Eames, MD    682-885-2580    Gretchen.eames@cookchildrens.org   
University of Texas/MD Anderson CRC Recruiting
Houston, Texas, United States, 77030
Contact: Amin M Alousi, MD    713-745-8613    aalousi@mdanderson.org   
Texas Transplant Institute Recruiting
San Antonio, Texas, United States, 78229
Contact: Paul Shaughnessy, MD    210-575-6907    paul.shaughnessy@mhshealth.com   
Contact: Carlos Bachier, MD    210-575-4238    Carlos.Bachier@MHShealth.com   
United States, Utah
Utah BMT/Primary Children's Medical Center Active, not recruiting
Salt Lake City, Utah, United States, 84132
United States, Virginia
Virginia Commonwealth University/MCV Hospitals Recruiting
Richmond, Virginia, United States, 23298
Contact: John M McCarty, MD    804-828-4360    jmccarty@hsc.vcu.edu   
United States, Washington
Fred Hutchinson Cancer Research Center Recruiting
Seattle, Washington, United States, 98109-1024
Contact: Paul A Carpenter, MB, MS       pcarpent@fhcrc.org   
United States, West Virginia
West Virginia University Hospital Not yet recruiting
Morgantown, West Virginia, United States, 26506-9162
United States, Wisconsin
University of Wisconsin Hospital and Clinics Recruiting
Madison, Wisconsin, United States, 53792-5156
Contact: Mark B Juckett, MD    608-263-1836    mbj@medicine.wisc.edu   
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53211
Contact: Monica Thakar, MD       mthakar@mcw.edu   
Contact: Jeanne Palmer, MD       jpalmer@mcw.edu   
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: May 29, 2013
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
Prednisone
Sirolimus
Everolimus
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on August 28, 2014