Sirolimus as Secondary Therapy in Chronic Graft-Versus-Host Disease Not Responding To Prior Treatment

NCT00079183 | Completed Phase 2 Results

• 2 other identifiers: 1706.00NCI-2011-01817
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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

Conditions

Graft Versus Host Disease

Outcome Measures

Primary Outcomes (4)

• Number of Participants Experiencing 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

• Number of Participants Experiencing 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

• Number of Participants Needing 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

• Number of Participants With 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

Secondary Outcomes (8)

• Proportion of Patients Who Discontinue Administration of Sirolimus Because of Toxicity

  Approximately 7 years

• Proportion With Infections Categorized by Organism

  Approximately 7 years

• Secondary Malignancies

  Up to 7 years

• Duration of Treatment With Prednisone

  Approximately 7 years

• Probability of Survival Without Recurrent Malignancy

  Approximately 7 years

Study Arms (1)

Sirolimus

EXPERIMENTAL

Study participants receive sirolimus added once daily to their baseline combination therapy of prednisone plus either cyclosporine or tacrolimus at the discretion of the managing physician. Treatment other than cyclosporine (or tacrolimus) and prednisone must be discontinued when administration of sirolimus is started. Topical therapy, including psoralen and UVA irradiation (PUVA), glucocorticoid creams, topical tacrolimus, oral beclomethasone, topical azathioprine and ophthalmic glucocorticoids may be given at the discretion of the managing physician in consultation with the transplant center.

Drug: sirolimus

Interventions

sirolimus DRUG

Given PO

Also known as: AY 22989, Rapamune, rapamycin, SLM

Sirolimus

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Dr. Paul A. Carpenter
• Organization: Fred Hutchinson Cancer Research Center

pcarpent@fredhutch.org

(206) 667-5191

Study Officials

• Paul Carpenter

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 8, 2004
• First Posted: March 10, 2004
• Study Start: April 1, 2002
• Primary Completion: July 1, 2009
• Study Completion: June 10, 2010
• Last Updated: June 20, 2017
• Results First Posted: May 12, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)