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

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00079183
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 44
• Location: 1
• Arm: 1
• Duration (Months): 98.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Graft Versus Host Disease	Drug: sirolimus	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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.

2. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• 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 Start Date: Apr 1, 2002
• Actual Primary Completion Date: Jul 1, 2009
• Actual Study Completion Date: Jun 10, 2010

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Sirolimus 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; Given PO; Other Names: AY 22989 Rapamune rapamycin SLM

Outcome Measures

Primary Outcome Measures

1. Number of Participants Experiencing Treatment Success [Approximately 7 years]

   Defined as the absence of any immunosuppressive treatment, including sirolimus, with resolution of all reversible manifestations of chronic GVHD and no additional systemic therapy.

2. Number of Participants Experiencing Treatment Failure [Approximately 7 years]

   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.

3. Number of Participants Needing Additional Systemic Therapy [Approximately 7 years]

   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.

4. Number of Participants With Recurrent Malignancy [Approximately 7 years]

   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.

Secondary Outcome Measures

1. Proportion of Patients Who Discontinue Administration of Sirolimus Because of Toxicity [Approximately 7 years]

2. Proportion With Infections Categorized by Organism [Approximately 7 years]

3. Secondary Malignancies [Up to 7 years]

   Proportion of participants who developed at least one secondary malignancy by 7 years

4. Duration of Treatment With Prednisone [Approximately 7 years]

5. Probability of Survival Without Recurrent Malignancy [Approximately 7 years]

   Kaplan-Meier estimate assessed at 7 years for probability of survival without recurrent malignancy.

6. Probability of Overall Survival [Approximately 7 years]

   Kaplan-Meier estimate assessed at 7 years

7. Probability of Cumulative Incidence of Death Without Recurrent Malignancy [Approximately 7 years]

   Analyzed with recurrent malignancy as a competing risk factor. Assessed at 7 years.

8. Probability of Cumulative Incidence of Recurrent Malignancy [Approximately 7 years]

   Analyzed with death as a competing risk factor. Assessed at 7 years.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Fred Hutchinson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Paul Carpenter, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Paul Carpenter, Principal Investigator, Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT00079183
• Other Study ID Numbers: 1706.00; NCI-2011-01817
• First Posted: Mar 10, 2004
• Last Update Posted: Jun 20, 2017
• Last Verified: May 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Graft vs Host Disease; Sirolimus

Study Results

Participant Flow

Arm/Group Title	Sirolimus
Arm/Group Description	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.
Period Title: Overall Study
STARTED	44
Drop Outs	7
COMPLETED	37
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	Sirolimus
Arm/Group Description	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.
Overall Participants	44
Age (Count of Participants)
<=18 years	14 31.8%
Between 18 and 65 years	26 59.1%
>=65 years	4 9.1%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	40.55
Sex: Female, Male (Count of Participants)
Female	18 40.9%
Male	26 59.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 4.5%
Not Hispanic or Latino	42 95.5%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 2.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 4.5%
White	39 88.6%
More than one race	2 4.5%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	44 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Experiencing Treatment Success
Description	Defined as the absence of any immunosuppressive treatment, including sirolimus, with resolution of all reversible manifestations of chronic GVHD and no additional systemic therapy.
Time Frame	Approximately 7 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sirolimus
Arm/Group Description	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.
Measure Participants	44
Count of Participants [Participants]	8 18.2%

2. Primary Outcome

Title	Number of Participants Experiencing Treatment Failure
Description	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.
Time Frame	Approximately 7 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sirolimus
Arm/Group Description	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.
Measure Participants	44
Count of Participants [Participants]	9 20.5%

3. Primary Outcome

Title	Number of Participants Needing Additional Systemic Therapy
Description	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.
Time Frame	Approximately 7 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sirolimus
Arm/Group Description	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. sirolimus: Given PO questionnaire administration: Ancillary studies quality-of-life assessment: Ancillary studies
Measure Participants	44
No additional therapy (off immunosuppressive Rx)	8 18.2%
Additional immunosuppressive therapy (IST) added	9 20.5%
Still on IST but no new IST added	27 61.4%

4. Primary Outcome

Title	Number of Participants With Recurrent Malignancy
Description	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.
Time Frame	Approximately 7 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sirolimus
Arm/Group Description	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.
Measure Participants	44
Count of Participants [Participants]	5 11.4%

5. Secondary Outcome

Title	Proportion of Patients Who Discontinue Administration of Sirolimus Because of Toxicity
Time Frame	Approximately 7 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sirolimus
Arm/Group Description	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.
Measure Participants	44
Count of Participants [Participants]	6 13.6%

6. Secondary Outcome

Title	Proportion With Infections Categorized by Organism
Time Frame	Approximately 7 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sirolimus
Arm/Group Description	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.
Measure Participants	44
Proportion of pts with at least 1 infection	21 47.7%
Proportion of pts with at least 1 bacterial inf'n	19 43.2%
Proportion of pts with at least 1 viral inf'n	6 13.6%
Proportion of pts with at least 1 fungal inf'n	4 9.1%
Proportion of pts with culture negative sepsis	1 2.3%

7. Secondary Outcome

Title	Secondary Malignancies
Description	Proportion of participants who developed at least one secondary malignancy by 7 years
Time Frame	Up to 7 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sirolimus
Arm/Group Description	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.
Measure Participants	44
Proportion with any second malignancy	15 34.1%
Proportion with any subsequent skin malignancy	13 29.5%
Proportion with subsequent oral malignancy	3 6.8%
Prop'n with subsequent prostate adenocarcinoma	1 2.3%
Prop'n with subsequent renal cell carcinoma	1 2.3%
Proportion with subsequent bladder carcinoma	1 2.3%
Prop'n with post-BMT lymphoproliferative disease	1 2.3%

8. Secondary Outcome

Title	Duration of Treatment With Prednisone
Time Frame	Approximately 7 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sirolimus
Arm/Group Description	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.
Measure Participants	44
Mean (Full Range) [Months]	45

9. Secondary Outcome

Title	Probability of Survival Without Recurrent Malignancy
Description	Kaplan-Meier estimate assessed at 7 years for probability of survival without recurrent malignancy.
Time Frame	Approximately 7 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sirolimus
Arm/Group Description	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.
Measure Participants	44
Number (95% Confidence Interval) [disease free survival probability]	0.54

10. Secondary Outcome

Title	Probability of Overall Survival
Description	Kaplan-Meier estimate assessed at 7 years
Time Frame	Approximately 7 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sirolimus
Arm/Group Description	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.
Measure Participants	44
Number (95% Confidence Interval) [survival probability]	0.59

11. Secondary Outcome

Title	Probability of Cumulative Incidence of Death Without Recurrent Malignancy
Description	Analyzed with recurrent malignancy as a competing risk factor. Assessed at 7 years.
Time Frame	Approximately 7 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sirolimus
Arm/Group Description	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.
Measure Participants	44
Number (95% Confidence Interval) [probability]	0.25

12. Secondary Outcome

Title	Probability of Cumulative Incidence of Recurrent Malignancy
Description	Analyzed with death as a competing risk factor. Assessed at 7 years.
Time Frame	Approximately 7 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sirolimus
Arm/Group Description	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.
Measure Participants	44
Number (95% Confidence Interval) [probability]	0.20

Adverse Events

Arm/Group Title	Sirolimus
Arm/Group Description	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.
All Cause Mortality
	Sirolimus
	Affected / at Risk (%)	# Events
Total	15/44 (34.1%)
Serious Adverse Events
	Sirolimus
	Affected / at Risk (%)	# Events
Total	22/44 (50%)
Blood and lymphatic system disorders
Hospitalized for Deep Vein Thrombosis (DVT)	2/44 (4.5%)	2
Hospitalized for Hemolytic-uremic syndrome (HUS)	2/44 (4.5%)	2
Hospitalized for Thrombotic Thrombocytopenic Purpura(TTP)	1/44 (2.3%)	1
Hospitalized for Idiopathic Thrombocytopenic Purpura (ITP)	1/44 (2.3%)	1
Hospitalized for Pancytopenia	1/44 (2.3%)	1
Cardiac disorders
Hospitalized for Congestive Heart Failure	1/44 (2.3%)	1
Hospitalized for Chest Pain	1/44 (2.3%)	1
Hospitalized for Hypertension	1/44 (2.3%)	1
Ear and labyrinth disorders
Hospitalized for Otitis Media	1/44 (2.3%)	1
Endocrine disorders
Hospitalized for Hyperglycemia	1/44 (2.3%)	1
Gastrointestinal disorders
Hospitalized for Dehydration	3/44 (6.8%)	3
Hospitalized for Refractory Diarrhea	1/44 (2.3%)	1
Hospitalized for Anorexia	1/44 (2.3%)	1
General disorders
Hospitalized for Fatigue	1/44 (2.3%)	1
Immune system disorders
Hospitalized for Vitamin K Deficiency	1/44 (2.3%)	1
Infections and infestations
Hospitalized for Fever	1/44 (2.3%)	1
Hospitalized for CMV (Cytomegalovirus Colitis) Enteritis	1/44 (2.3%)	1
Hospitalized for Coag Negative Staph Bacteremia	3/44 (6.8%)	3
Hospitalized for Pneumonia	10/44 (22.7%)	10
Hospitalized for Enterobacter Bacteremia	3/44 (6.8%)	3
Hospitalized for Pseudomonas Aeruginosa Bacteremia	1/44 (2.3%)	1
Hospitalized for Streptococcus Viridans Bacteremia	2/44 (4.5%)	2
Hospitalization for Candida Parapsilosis	1/44 (2.3%)	1
Hospitalized for Septic Shock	1/44 (2.3%)	1
Hospitalized for Sinusitis	3/44 (6.8%)	4
Hospitalized for C. Difficile	1/44 (2.3%)	1
Hospitalized for Parainfluenza	1/44 (2.3%)	1
Hospitalization for Respiratory Syncytial Virus	2/44 (4.5%)	2
Hospitalization for Chicken Pox	1/44 (2.3%)	1
Hospitalization for Staphylococcus aureus	1/44 (2.3%)	1
Hospitalization for CMV Mucositis	1/44 (2.3%)	1
Hospitalization for Haemophilus influenzae	1/44 (2.3%)	1
Hospitalization for Staphylococcus epidermidis	1/44 (2.3%)	1
Hospitalization for Micrococcus bacteremia	1/44 (2.3%)	1
Hospitalization for Staphylococcus Hickman Site Infection	1/44 (2.3%)	1
Musculoskeletal and connective tissue disorders
Hospitalization for Hip Replacement	1/44 (2.3%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hospitalized for tumor in back (relapse)	1/44 (2.3%)	1
Nervous system disorders
Hospitalized for Dizziness	1/44 (2.3%)	1
Renal and urinary disorders
Hospitalized for Renal Insufficiency	4/44 (9.1%)	4
Hospitalized for Oliguric Failure	1/44 (2.3%)	1
Respiratory, thoracic and mediastinal disorders
Hospitalized for Chylothorax	1/44 (2.3%)	1
Surgical and medical procedures
Hospitalized for GVHD Flare	3/44 (6.8%)	3
Other (Not Including Serious) Adverse Events
	Sirolimus
	Affected / at Risk (%)	# Events
Total	30/44 (68.2%)
Blood and lymphatic system disorders
Neutropenia	4/44 (9.1%)	6
Anemia	2/44 (4.5%)	2
Thrombocytopenia	4/44 (9.1%)	4
Cardiac disorders
Hypertension	4/44 (9.1%)	4
Endocrine disorders
Diabetic Foot Ulcers	1/44 (2.3%)	1
Eye disorders
Eye Infection	2/44 (4.5%)	2
Gastrointestinal disorders
Diarrhea	5/44 (11.4%)	6
Nausea	3/44 (6.8%)	3
Vomiting	3/44 (6.8%)	3
General disorders
Fatigue	1/44 (2.3%)	1
Infections and infestations
Bronchitis	3/44 (6.8%)	3
Pneumonia	2/44 (4.5%)	3
C. Difficile	2/44 (4.5%)	3
Shingles	1/44 (2.3%)	1
sinusitis	5/44 (11.4%)	5
Otitis Media	2/44 (4.5%)	3
Chicken Pox	1/44 (2.3%)	1
Strep Throat	2/44 (4.5%)	2
Coag Negative Staph	1/44 (2.3%)	1
Left Parotid Gland Infection	1/44 (2.3%)	1
Pseudomonas aeruginosa	1/44 (2.3%)	1
Aspergillus	1/44 (2.3%)	1
BK Virus	1/44 (2.3%)	1
Metabolism and nutrition disorders
Hyperlipidemia	11/44 (25%)	12
Musculoskeletal and connective tissue disorders
Osteoporosis	3/44 (6.8%)	3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal and Squamous Cell	3/44 (6.8%)	5
Urinary Bladder Tumor	1/44 (2.3%)	1
Nervous system disorders
Depression	4/44 (9.1%)	4
Renal and urinary disorders
Renal Insufficiency	10/44 (22.7%)	12
Skin and subcutaneous tissue disorders
Lower Extremity Edema	12/44 (27.3%)	12

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.