Sirolimus as Secondary Therapy in Treating Patients With Chronic Graft-Versus-Host Disease That Did Not Respond To Prior Treatment

Graft Versus Host Disease Clinical Trial

Official title:

A Phase II Clinical Trial to Evaluate the Safety and Efficacy of Sirolimus for Secondary Treatment of Chronic Graft-versus-Host Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00079183
• Other study ID #: 1706.00
• Secondary ID: NCI-2011-01817
• Status: Completed
• Phase: Phase 2
• First received: March 8, 2004
• Last updated: March 13, 2012
• Start date: April 2002

Study information

• Verified date: March 2012
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Graft Versus Host Disease
• Graft vs Host Disease

Intervention

Drug:
• sirolimus
Given PO

Other:
• questionnaire administration
Ancillary studies

Procedure:
• quality-of-life assessment
Ancillary studies

Locations

Country	Name	City	State
United States	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment success	Defined as the absence of any immunosuppressive treatment, including sirolimus, with resolution of all reversible manifestations of chronic GVHD and no additional systemic therapy.	Approximately 7 years	No
Primary	Treatment failure	Defined as the initiation of additional systemic therapy, development of bronchiolitis obliterans, or death from causes other than recurrent malignancy during primary treatment for chronic GVHD, whichever occurs first.	Approximately 7 years	No
Primary	Additional systemic therapy	Includes any intervention intended to control chronic GVHD through an immunosuppressive effect from oral or parenteral administration of any systemic medication not originally given under auspices of this protocol.	Approximately 7 years	No
Primary	Recurrent malignancy	Defined as clinical or histopathologic evidence demonstrating the presence of any malignancy considered as the indication for transplant. Recurrent malignancy will also be defined as any post-transplant intervention not routinely used to prevent the development of overt recurrence, prompted by laboratory evidence of persisting malignant cells but without clinical or histopathologic evidence of recurrence.	Approximately 7 years	No
Secondary	Proportion of patients who discontinue administration of sirolimus because of toxicity		Every 3 months	Yes
Secondary	Incidence of infections categorized by organism		Every 3 months	Yes
Secondary	Incidence of secondary malignancies categorized by type (lymphoma, lymphoproliferative disorders, skin cancers other than melanoma, other types of tumors)		Every 3 months	Yes
Secondary	Duration of treatment with prednisone		Approximately 7 years	No
Secondary	Proportion of patients with treatment success		Approximately 7 years	No
Secondary	Survival without recurrent malignancy		Approximately 7 years	No
Secondary	Overall survival		Approximately 7 years	No
Secondary	Cumulative incidence of secondary systemic treatment for chronic GVHD before recurrent malignancy		Approximately 7 years	No
Secondary	Cumulative incidence of death without recurrent malignancy		Approximately 7 years	No
Secondary	Cumulative incidence of recurrent malignancy		Approximately 7 years	No