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

NCT00388362 | Completed Phase 2 Results DMC

• 3 other identifiers: IRB-358796589BMT175
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Graft vs Host Disease

Keywords

GVHD

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Overall Survival

  3 month intervals after the initiation of sirolimus until 2 years after the initiation of sirolimus

Study Arms (1)

Sirolimus Therapy

EXPERIMENTAL

Administration of Sirolimus and Prednisone

Drug: Sirolimus; Drug: Prednisone

Interventions

Sirolimus 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.

Also known as: Rapamune

Sirolimus Therapy

Prednisone 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.

Also known as: Deltasone

Sirolimus Therapy

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Sirolimus; Prednisone

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Laura Johnston, MD
• Organization: Stanford University

janices1@stanford.edu

650-723-0822

Study Officials

• Laura Johnston

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: October 12, 2006
• First Posted: October 16, 2006
• Study Start: November 1, 2005
• Primary Completion: November 1, 2010
• Study Completion: August 1, 2012
• Last Updated: April 21, 2017
• Results First Posted: April 21, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)