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

NCT ID: NCT00388362

Last Updated: 2017-04-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-11-30
• Study Completion Date: 2012-08-31

Brief Summary

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

Conditions

Graft vs Host Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sirolimus Therapy

Administration of Sirolimus and Prednisone

Group Type: EXPERIMENTAL

Sirolimus

Intervention Type: DRUG

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.

Prednisone

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Rapamune; Deltasone

Eligibility 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

• Minimum Eligible Age: 13 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Laura Johnston

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Laura Johnston

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University School of Medicine

Stanford, California, United States

Countries

United States

Other Identifiers

96589

Identifier Type: OTHER

Identifier Source: secondary_id

BMT175

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-3587

Identifier Type: -

Identifier Source: org_study_id