Clinical trial NCT00388362: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Graft vs Host Disease
Keywords: GVHD
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2006-10-16
Enrollment: 36
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Clinical Activity
timeFrame: 3 month intervals after the initiation of sirolimus until 2 years after the initiation of sirolimus
Secondary outcomes:
measure: Overall Survival
timeFrame: 3 month intervals after the initiation of sirolimus until 2 years after the initiation of sirolimus
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Laura Johnston
role: PRINCIPAL_INVESTIGATOR
References: