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

• ClinicalTrials.gov Identifier: NCT00388362
• Recruitment Status: Completed
• First Posted: October 16, 2006
• Results First Posted: April 21, 2017
• Last Update Posted: April 21, 2017
• Sponsor: Stanford University
• Information provided by (Responsible Party): Laura Johnston, Stanford University

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Graft vs Host Disease	Drug: Sirolimus; Drug: Prednisone	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Sirolimus as Treatment of Steroid-Refractory or Steroid-Dependent Chronic Graft-Versus-Host Disease
• Study Start Date: November 2005
• Actual Primary Completion Date: November 2010
• Actual Study Completion Date: August 2012

Arms and Interventions

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 Name: 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 Name: Deltasone

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Overall Survival [ Time Frame: 3 month intervals after the initiation of sirolimus until 2 years after the initiation of sirolimus ]
   Administration of Sirolimus and Prednisone

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

Stanford University School of Medicine

Stanford, California, United States, 94305

Sponsors and Collaborators

Stanford University

Investigators

• Principal Investigator: Laura Johnston; Stanford University

More Information

• Responsible Party: Laura Johnston, Associate Professor of Medicine, Stanford University
• ClinicalTrials.gov Identifier: NCT00388362
• Other Study ID Numbers: IRB-3587; 96589 ( Other Identifier: Stanford University Alternate IRB Approval Number ); BMT175 ( Other Identifier: OnCore Number )
• First Posted: October 16, 2006
• Results First Posted: April 21, 2017
• Last Update Posted: April 21, 2017
• Last Verified: March 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Laura Johnston, Stanford University:

GVHD

Additional relevant MeSH terms:

Graft vs Host Disease; Immune System Diseases; Sirolimus; Prednisone; 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