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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01106833
First Posted: April 20, 2010
Last Update Posted: February 9, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
National Cancer Institute (NCI)
Blood and Marrow Transplant Clinical Trials Network
National Marrow Donor Program
Information provided by (Responsible Party):
Medical College of Wisconsin
  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
Intervention Model: Parallel Assignment
Masking: None (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; Phase III: Proportion of subjects with Complete Response; resolution of graft versus host disease manifestations [ Time Frame: Phase II: 6 months; Phase III: 24 months ]

Secondary Outcome Measures:
  • Phase II: Avg. daily dose % reduction of prednisone [ Time Frame: 6 and 12 months ]
  • Phase II: Cumulative incidence of treatment failure [ Time Frame: 1 year ]
  • Phase II: Prevalence of active symptomatic chronic GVHD [ Time Frame: 1 and 2 years ]
  • Phase II: Incidence of discontinuation of all systemic immunosuppressive therapy [ Time Frame: 1 and 2 years ]
  • Phase II: Overall and cancer progression-free survival [ Time Frame: 1 and 2 years ]
  • Phase II: Serum biomarkers of chronic GVHD [ Time Frame: baseline, 2 and 6 months ]
  • Phase III: Avg. daily dose % reduction of prednisone [ Time Frame: 6, 12 and 24 months ]
  • Phase III: Cumulative incidence of treatment failure [ Time Frame: 1 and 2 years ]
  • Phase III: Prevalence of active symptomatic chronic GVHD [ Time Frame: 1 and 2 years ]
  • Phase III: Incidence of discontinuation of all systemic immunosuppressive therapy [ Time Frame: 1 and 2 years ]
  • Phases III: Overall and cancer progression-free survival [ Time Frame: 1 and 2 years ]
  • Phase III: Serum biomarkers of chronic GVHD [ Time Frame: baseline, 1 and 2 years ]

Enrollment: 161
Actual 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: calcineurin inhibitor
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 and 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

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01106833


  Show 31 Study Locations
Sponsors and Collaborators
Medical College of Wisconsin
National Heart, Lung, and Blood Institute (NHLBI)
National Cancer Institute (NCI)
Blood and Marrow Transplant Clinical Trials Network
National Marrow Donor Program
Investigators
Study Director: Mary Horowitz, MD Center for International Blood and Marrow Transplant Research
  More Information

Additional Information:
Responsible Party: Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT01106833     History of Changes
Other Study ID Numbers: BMTCTN0801
U01HL069294 ( U.S. NIH Grant/Contract )
BMT CTN 0801 ( Other Identifier: Blood and Marrow Transplant Clinical Trials Network )
U01HL06929406 ( Other Grant/Funding Number: National Cancer Institute (NCI) )
5U24CA076518 ( U.S. NIH Grant/Contract )
First Submitted: April 16, 2010
First Posted: April 20, 2010
Last Update Posted: February 9, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Findings will be published in a manuscript

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
Calcineurin Inhibitors
Anti-Inflammatory Agents
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
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action


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