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

NCT01106833 | Completed Phase 2 Results DMC

• 5 other identifiers: BMTCTN0801U01HL069294BMT CTN 0801U01HL069294065U24CA076518
• Study Type: interventional
• Target: 151
• Locations: 1 country
• Sites: 31

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.

Conditions

Chronic GVHD

Keywords

Chronic Graft-versus-Host Disease (cGVHD)

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants With Treatment Success

  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.

  6 months and 24 months post-randomization

Secondary Outcomes (16)

• Percentage of Participants With Overall Survival

  6 months and 24 months post-randomization

• Percentage of Participants With Progression-free Survival

  6 months and 24 months post-randomization

• Percentage of Participants With Failure-free Survival

  6 months and 24 months post-randomization

• Percentage of Participants With Relapse

  6 months and 24 months post-randomization

• Percentage of Participants With Secondary Immunosuppressive Therapy Initiated

  6 months and 24 months post-randomization

Study Arms (2)

calcineurin inhibitor

ACTIVE COMPARATOR

Sirolimus + calcineurin inhibitor + prednisone

Drug: Sirolimus + calcineurin inhibitor + prednisone

Sirolimus and prednisone

EXPERIMENTAL

Sirolimus + prednisone

Drug: Sirolimus + prednisone

Interventions

Sirolimus + calcineurin inhibitor + prednisone DRUG

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.

Also known as: Rapamune, Prograf, Neorall, Gengraf

calcineurin inhibitor

Sirolimus + prednisone DRUG

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.

Also known as: Rapamune

Sirolimus and prednisone

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Medical College of Wisconsin: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• National Cancer Institute (NCI): collaborator
• Blood and Marrow Transplant Clinical Trials Network: collaborator
• National Marrow Donor Program: collaborator

Study Sites (31)

City of Hope National Medical Center

Duarte, California, 91010-3000, United States

Location

University of California San Diego Medical Center

La Jolla, California, 92093, United States

Location

Stanford Hospital and Clinics

Stanford, California, 94305, United States

Location

University of Florida College of Medicine (Shands)

Gainesville, Florida, 32610-0277, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Blood & Marrow Transplant Program at Northside Hospital

Atlanta, Georgia, 30342, United States

Location

University of Chicago

Chicago, Illinois, 60637-1470, United States

Location

University of Kansas Hospital

Kansas City, Kansas, 66160, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21231, United States

Location

University of Michigan Medical Center

Ann Arbor, Michigan, 48105-2967, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University, Barnes Jewish Hospital

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198-7680, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10174, United States

Location

Mayo Clinic

Rochester, New York, 55905, United States

Location

University of North Carolina Hospital at Chapel Hill

Chapel Hill, North Carolina, 27599-7305, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Jewish Hospital BMT Program

Cincinnati, Ohio, 45236, United States

Location

University Hospitals of Cleveland/ Case Western

Cleveland, Ohio, 44106-5061, United States

Location

University of Oklahoma Medical Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oregon Health & Science University (A) and (P)

Portland, Oregon, 97239-3098, United States

Location

University of Pennsylvania Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, 15224, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

University of Texas/MD Anderson CRC

Houston, Texas, 77030, United States

Location

Texas Transplant Institute

San Antonio, Texas, 78229, United States

Location

Virginia Commonwealth University/MCV Hospitals

Richmond, Virginia, 23298, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109-1024, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792-5156, United States

Location

Related Publications (2)

• 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. doi: 10.1016/j.bbmt.2005.09.004.

  PMID: 16338616 BACKGROUND

• Carpenter PA, Logan BR, Lee SJ, Weisdorf DJ, Johnston L, Costa LJ, Kitko CL, Bolanos-Meade J, Sarantopoulos S, Alousi AM, Abhyankar S, Waller EK, Mendizabal A, Zhu J, O'Brien KA, Lazaryan A, Wu J, Nemecek ER, Pavletic SZ, Cutler CS, Horowitz MM, Arora M; BMT CTN.. A phase II/III randomized, multicenter trial of prednisone/sirolimus versus prednisone/ sirolimus/calcineurin inhibitor for the treatment of chronic graft-versus-host disease: BMT CTN 0801. Haematologica. 2018 Nov;103(11):1915-1924. doi: 10.3324/haematol.2018.195123. Epub 2018 Jun 28.

  PMID: 29954931 DERIVED

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Interventions

Sirolimus; Calcineurin Inhibitors; Prednisone; Tacrolimus; Cyclosporins

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Peptides, Cyclic; Macrocyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Adam Mendizabal, PhD
• Organization: The Emmes Corporation

amendizabal@emmes.com

301-251-1161

Study Officials

• Mary Horowitz, MD

  Center for International Blood and Marrow Transplant Research

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2010
• First Posted: April 20, 2010
• Study Start: April 1, 2010
• Primary Completion: February 14, 2017
• Study Completion: June 1, 2018
• Last Updated: December 5, 2018
• Results First Posted: August 14, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will share
• Time Frame: Within 6 months of official study closure at participating sites.
• Access Criteria: Available to the public

Locations

US (31)