Sirolimus as Treatment of Steroid-Refractory or Steroid-Dependent Chronic Graft-Versus-Host Disease

A Phase II Trial of Sirolimus as Treatment of Steroid-Refractory or Steroid-Dependent Chronic Graft-Versus-Host Disease

To study the effectiveness of an immunosuppressive drug sirolimus, in the treatment of chronic graft versus host disease in combination with prednisone.

Study Overview

• Status: Completed
• Conditions: Graft vs Host Disease
• Intervention / Treatment: Drug: Sirolimus; Drug: Prednisone

Detailed Description

The purpose of this trial is to study the effectiveness of an immunosuppressive drug, sirolimus, in the treatment of chronic graft versus host disease in combination with prednisone. Graft versus host disease (GVHD) is a common complication in patients who have received blood or marrow transplantation from a related or unrelated donor. Chronic GVHD occurs approximately 100 days after transplantation and is the result of the donor immune system recognizing the patient's tissues as foreign and creating harmful effects on the patient's organs. We hope the use of sirolimus will decrease the significant disabling effects and deaths caused by chronic GVHD.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 13 years
• Weight ≥ 40 kg.
• Biopsy or clinical presentation diagnostic of chronic GVHD >100 days following allogeneic bone marrow/peripheral blood/umbilical cord blood transplantation that has failed prior corticosteroid therapy or corticosteroid taper. In the event that histological confirmation poses undue risk, clinical evaluation is sufficient.
• Women of child-bearing potential must have a negative pregnancy test before sirolimus administration and agree to use a medically acceptable contraceptive throughout the treatment period until 3 months after discontinuation of sirolimus.
• Any woman becoming pregnant during the treatment period must discontinue the use of sirolimus.
• Absolute neutrophil count (ANC) > 1000/mm³, unless receiving G-CSF to maintain neutrophil count > 500/mm³.
• At the time of initiating sirolimus the cyclosporine trough level is recommended to be < 100 mg/dl and FK506 level is recommended to be < 5 mg/dl. FK506 or cyclosporine is to be discontinued soon after initiation of sirolimus.
• Karnofsky performance score ≥ 50 during pre-study screening.
• Written, signed, and dated informed consent

Exclusion Criteria:

• Uncontrolled systemic infection
• Unstable disease states (i.e., hepatic failure, ventilatory-dependent respiratory failure, etc.)
• Serum creatinine ≥ 3.0 mg/dL
• Platelet count ≤ 50,000/mm³
• History of Post-transplant microangiopathic hemolytic anemia
• Uncontrolled hyperlipidemia
• Use of any investigational drug within 4 weeks of entry into the study
• Use of methotrexate or antibody therapies within 24 hours of sirolimus administration
• Inability to tolerate oral therapy for any reason
• Evidence of infiltrate, cavitation, or consolidation on chest x-ray during pre-study screening
• Known hypersensitivity to macrolide antibiotics

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Sirolimus Therapy; Administration of Sirolimus and Prednisone

Drug: Sirolimus; Patients will receive sirolimus at 2 mg/day orally with monitoring of trough drug levels weekly for 2 weeks to achieve trough drug levels 7-12 ng/ml. Along with prednisone therapy.; Other Names: Rapamune; Drug: Prednisone; Prednisone therapy will remain at the dose the patient received at the time sirolimus was begun. Withdrawal of prednisone will began after first evidence of improvement of chronic GVHD.; Other Names: Deltasone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Activity	Determined by discontinuation of immunosuppression with resolution of all reversible CGVHD manifestations. Evaluated at 2 years after enrollment	3 month intervals after the initiation of sirolimus until 2 years after the initiation of sirolimus

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Administration of Sirolimus and Prednisone	3 month intervals after the initiation of sirolimus until 2 years after the initiation of sirolimus

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Laura Johnston, Stanford University

Study record dates

Study Major Dates

• Study Start: November 1, 2005
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: October 12, 2006
• First Submitted That Met QC Criteria: October 13, 2006
• First Posted (Estimate): October 16, 2006

Study Record Updates

• Last Update Posted (Actual): April 21, 2017
• Last Update Submitted That Met QC Criteria: March 13, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: GVHD
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Physiological Effects of Drugs; Anti-Infective Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Prednisone; Sirolimus
• Other Study ID Numbers: IRB-3587; 96589 (Other Identifier: Stanford University Alternate IRB Approval Number); BMT175 (Other Identifier: OnCore Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO