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

  Show 53 Study Locations
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
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 July 26, 2014