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

Primary Purpose

Graft vs Host Disease

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Sirolimus

Prednisone

About this trial

This is an interventional treatment trial for Graft vs Host Disease focused on measuring GVHD

Eligibility Criteria

13 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Stanford University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sirolimus Therapy

Arm Description

Administration of Sirolimus and Prednisone

Outcomes

Primary Outcome Measures

Clinical Activity

Determined by discontinuation of immunosuppression with resolution of all reversible CGVHD manifestations. Evaluated at 2 years after enrollment

Secondary Outcome Measures

Overall Survival

Administration of Sirolimus and Prednisone

Full Information

NCT ID

NCT00388362

First Posted

October 12, 2006

Last Updated

March 13, 2017

Sponsor

Stanford University

1. Study Identification

Unique Protocol Identification Number

NCT00388362

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2017

Overall Recruitment Status

Completed

Study Start Date

November 2005 (undefined)

Primary Completion Date

November 2010 (Actual)

Study Completion Date

August 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Stanford University

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Graft vs Host Disease

Keywords

GVHD

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

36 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sirolimus Therapy

Arm Type

Experimental

Arm Description

Administration of Sirolimus and Prednisone

Intervention Type

Drug

Intervention Name(s)

Sirolimus

Other Intervention Name(s)

Rapamune

Intervention Description

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

Intervention Name(s)

Prednisone

Other Intervention Name(s)

Deltasone

Intervention Description

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.

Primary Outcome Measure Information:

Title

Clinical Activity

Description

Determined by discontinuation of immunosuppression with resolution of all reversible CGVHD manifestations. Evaluated at 2 years after enrollment

Time Frame

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

Secondary Outcome Measure Information:

Title

Overall Survival

Description

Administration of Sirolimus and Prednisone

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

13 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Laura Johnston

Organizational Affiliation

Stanford University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Stanford University School of Medicine

City

Stanford

State/Province

California

ZIP/Postal Code

94305

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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