Clinical trial NCT00079183: Sirolimus as Secondary Therapy in Chronic Graft-Versus-Host Disease Not Responding To Prior Treatment
Official title: A Phase II Clinical Trial to Evaluate the Safety and Efficacy of Sirolimus for Secondary Treatment of Chronic Graft-versus-Host Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Graft Versus Host Disease
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-03-10
Enrollment: 44
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: This phase II trial studies the side effects and how well sirolimus works as secondary therapy in treating patients with chronic graft-versus-host disease (GVHD) that did not respond to prior treatment. Sirolimus may be an effective treatment for chronic GVHD

Detailed description: PRIMARY OBJECTIVES:

I. To assess the safety of sirolimus administered at a dose which provides steady-state, whole blood trough levels of 5-10 ng/mL in patients with chronic GVHD.

II. To determine whether administration of sirolimus provides benefit for patients with chronic GVHD that has not responded adequately to previous systemic treatment.

OUTLINE:

Patients receive sirolimus orally (PO) once daily (QD). Patients continue to receive prednisone and cyclosporine or tacrolimus at the discretion of the managing physician.

After completion of study treatment, patients are followed up periodically.

Eligibility criteria: Inclusion Criteria:

* Biopsy-confirmed diagnosis of clinical extensive chronic GVHD with inadequate response to previous treatment and where secondary systemic therapy is indicated because of

  * Clinical progression of signs and symptoms of chronic GVHD in a previously involved organ, or
  * Development of signs and symptoms of chronic GVHD in a previously uninvolved organ, or
  * Absence of improvement after 3 months of primary treatment, or
  * Continued need for treatment with prednisone at doses \>= 1.0 mg/kg/day for more than 2 months, without qualification for type of donor, graft or conditioning regimen
* Patient or guardian able and willing to provide informed consent
* Stated willingness to use contraception in women of child-bearing potential (Food and Drug Administration \[FDA\] requirement)
* Stated willingness of the patient to comply with study procedures and reporting requirements
* Stated willingness of the physician most involved in management of chronic GVHD (the "managing physician,") to comply with study procedures and reporting requirements

Exclusion Criteria:

* Fungal or viral infection with no radiographic evidence of improvement during continued appropriate antimicrobial therapy
* Cytomegalovirus (CMV) antigenemia unresponsive to antiviral therapy
* Active disseminated varicella zoster virus (VZV) infection with persistent non-crusted lesions
* Inability to tolerate oral medications
* Absolute neutrophil count (ANC) \< 1500/uL
* Platelet count \< 50,000/uL
* Persistent or recurrent malignancy, including histopathologic evidence of myeloma or lymphoma; patients with breakpoint cluster region-abelson (bcr/abl) detected by polymerase chain reaction (PCR) assay as the only evidence of persistent chronic myeloid leukemia may be enrolled
* Pregnancy
* Known history of hypersensitivity to sirolimus

Primary outcomes:
measure: Number of Participants Experiencing Treatment Success
timeFrame: Approximately 7 years
measure: Number of Participants Experiencing Treatment Failure
timeFrame: Approximately 7 years
measure: Number of Participants Needing Additional Systemic Therapy
timeFrame: Approximately 7 years
measure: Number of Participants With Recurrent Malignancy
timeFrame: Approximately 7 years
Secondary outcomes:
measure: Proportion of Patients Who Discontinue Administration of Sirolimus Because of Toxicity
timeFrame: Approximately 7 years
measure: Proportion With Infections Categorized by Organism
timeFrame: Approximately 7 years
measure: Secondary Malignancies
timeFrame: Up to 7 years
measure: Duration of Treatment With Prednisone
timeFrame: Approximately 7 years
measure: Probability of Survival Without Recurrent Malignancy
timeFrame: Approximately 7 years
measure: Probability of Overall Survival
timeFrame: Approximately 7 years
measure: Probability of Cumulative Incidence of Death Without Recurrent Malignancy
timeFrame: Approximately 7 years
measure: Probability of Cumulative Incidence of Recurrent Malignancy
timeFrame: Approximately 7 years
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
state: Washington
Study officials:
affiliation: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
name: Paul Carpenter
role: PRINCIPAL_INVESTIGATOR
References: