Chronic Graft-versus-Host Disease Treatment (BMT CTN 0801)
This study is currently recruiting participants.
Verified April 2013 by Medical College of Wisconsin
Sponsor:
Medical College of Wisconsin
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: April 2, 2013
Last verified: April 2013
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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:
Drug Information available for:
Prednisone
Sirolimus
Cyclosporine
Tacrolimus
Everolimus
Temsirolimus
U.S. FDA Resources
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:
|
| 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); 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 < 12 years). Adults: eCCr (mL/min/1.73 m^2) = (140 - age) x mass (kg) x (0.85 if female)/72 x serum creatinine (mg/dL; 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01106833
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Contacts
| Contact: Mary Horowitz, MD, MS | marymh@mcw.edu |
Hide Study LocationsLocations
| United States, Alabama | |
| University of Alabama at Birmingham | Not yet recruiting |
| Birmingham, Alabama, United States, 35294 | |
| 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 | |
| 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 | Recruiting |
| Iowa City, Iowa, United States, 52242-1009 | |
| Contact: Margarida Silverman, MD 319-384-9156 margarida-silverman@uiowa.edu | |
| 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: Gorgun Akpek, MD, MHS gakpek@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 | Recruiting |
| Boston, Massachusetts, United States, 02115 | |
| Contact: Corey Cutler, MD, MPH, FRC 617-632-5946 cscutler@partners.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 | Not yet recruiting |
| Detroit, Michigan, United States, 48201 | |
| 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 | Not yet recruiting |
| Buffalo, New York, United States, 14263 | |
| 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 | Recruiting |
| New York, New York, United States, 10029 | |
| Contact: Eileen Scigliano, MD 212-241-6021 eileen.scigliano@mountsinai.org | |
| 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 | Recruiting |
| Philadelphia, Pennsylvania, United States, 19111-2442 | |
| Contact: Robert Emmons, MD 215-214-3125 Robert.Emmons@tuhs.temple.edu | |
| University of Pennsylvania Cancer Center | Recruiting |
| Philadelphia, Pennsylvania, United States, 19104 | |
| Contact: David Porter, MD 215-662-2867 David.porter@uphs.upenn.edu | |
| 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 | Recruiting |
| Salt Lake City, Utah, United States, 84132 | |
| Contact: Michael Pulsipher, MD 801-585-3229 michael.pulsipher@hsc.utah.edu | |
| 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 | |
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: | April 2, 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 Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Pharmacologic Actions |
Antineoplastic Agents, Hormonal Antineoplastic Agents Therapeutic Uses Anti-Inflammatory Agents Antibiotics, Antineoplastic Antifungal Agents Anti-Infective Agents Immunosuppressive Agents Immunologic Factors Anti-Bacterial Agents |
ClinicalTrials.gov processed this record on May 23, 2013