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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2011-01817 | Registry Identifier | CTRP (Clinical Trial Reporting Program) |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| sirolimus | Drug | Given PO |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Patients Who Discontinue Administration of Sirolimus Because of Toxicity | Approximately 7 years | |
| Proportion With Infections Categorized by Organism | Approximately 7 years | |
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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
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:
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| Name | Affiliation | Role |
|---|---|---|
| Paul Carpenter | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Seattle | Washington | 98109 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
This includes all 44 consented subjects.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Count of Participants | Participants | Approximately 7 years |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hospitalized for Congestive Heart Failure | Cardiac disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Paul A. Carpenter | Fred Hutchinson Cancer Research Center | (206) 667-5191 | pcarpent@fredhutch.org |
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| ID | Term |
|---|---|
| D006086 | Graft vs Host Disease |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D020123 | Sirolimus |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
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| Secondary Malignancies |
Proportion of participants who developed at least one secondary malignancy by 7 years |
| Up to 7 years |
| Duration of Treatment With Prednisone | Approximately 7 years |
| Probability of Survival Without Recurrent Malignancy | Kaplan-Meier estimate assessed at 7 years for probability of survival without recurrent malignancy. | Approximately 7 years |
| Probability of Overall Survival | Kaplan-Meier estimate assessed at 7 years | Approximately 7 years |
| Probability of Cumulative Incidence of Death Without Recurrent Malignancy | Analyzed with recurrent malignancy as a competing risk factor. Assessed at 7 years. | Approximately 7 years |
| Probability of Cumulative Incidence of Recurrent Malignancy | Analyzed with death as a competing risk factor. Assessed at 7 years. | Approximately 7 years |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
|
|
|
| Primary | 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. | Posted | Count of Participants | Participants | Approximately 7 years |
|
|
|
| Primary | 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. | Posted | Count of Participants | Participants | Approximately 7 years |
|
|
|
| Primary | 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. | Posted | Count of Participants | Participants | Approximately 7 years |
|
|
|
| Secondary | Proportion of Patients Who Discontinue Administration of Sirolimus Because of Toxicity | Posted | Count of Participants | Participants | Approximately 7 years |
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|
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| Secondary | Proportion With Infections Categorized by Organism | Posted | Count of Participants | Participants | Approximately 7 years |
|
|
|
| Secondary | Secondary Malignancies | Proportion of participants who developed at least one secondary malignancy by 7 years | Posted | Count of Participants | Participants | Up to 7 years |
|
|
|
| Secondary | Duration of Treatment With Prednisone | Posted | Mean | Full Range | Months | Approximately 7 years |
|
|
|
| Secondary | Probability of Survival Without Recurrent Malignancy | Kaplan-Meier estimate assessed at 7 years for probability of survival without recurrent malignancy. | Posted | Number | 95% Confidence Interval | disease free survival probability | Approximately 7 years |
|
|
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| Secondary | Probability of Overall Survival | Kaplan-Meier estimate assessed at 7 years | Posted | Number | 95% Confidence Interval | survival probability | Approximately 7 years |
|
|
|
| Secondary | Probability of Cumulative Incidence of Death Without Recurrent Malignancy | Analyzed with recurrent malignancy as a competing risk factor. Assessed at 7 years. | Posted | Number | 95% Confidence Interval | probability | Approximately 7 years |
|
|
|
| Secondary | Probability of Cumulative Incidence of Recurrent Malignancy | Analyzed with death as a competing risk factor. Assessed at 7 years. | Posted | Number | 95% Confidence Interval | probability | Approximately 7 years |
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|
| 15 |
| 44 |
| 22 |
| 44 |
| 30 |
| 44 |
| Hospitalized for Chest Pain | Cardiac disorders | Non-systematic Assessment |
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| Hospitalized for Deep Vein Thrombosis (DVT) | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Hospitalized for Hemolytic-uremic syndrome (HUS) | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Hospitalized for Hypertension | Cardiac disorders | Non-systematic Assessment |
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| Hospitalized for Thrombotic Thrombocytopenic Purpura(TTP) | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Hospitalized for Idiopathic Thrombocytopenic Purpura (ITP) | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Hospitalized for Fever | Infections and infestations | Non-systematic Assessment |
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| Hospitalized for Fatigue | General disorders | Non-systematic Assessment |
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| Hospitalized for Dizziness | Nervous system disorders | Non-systematic Assessment |
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| Hospitalized for Dehydration | Gastrointestinal disorders | Non-systematic Assessment |
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| Hospitalized for Refractory Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
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| Hospitalized for GVHD Flare | Surgical and medical procedures | Non-systematic Assessment | Graft vs. Host Disease |
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| Hospitalized for Vitamin K Deficiency | Immune system disorders | Non-systematic Assessment |
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| Hospitalized for CMV (Cytomegalovirus Colitis) Enteritis | Infections and infestations | Non-systematic Assessment |
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| Hospitalized for Coag Negative Staph Bacteremia | Infections and infestations | Non-systematic Assessment |
|
| Hospitalized for Pneumonia | Infections and infestations | Non-systematic Assessment |
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| Hospitalized for Enterobacter Bacteremia | Infections and infestations | Non-systematic Assessment |
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| Hospitalized for Pseudomonas Aeruginosa Bacteremia | Infections and infestations | Non-systematic Assessment |
|
| Hospitalized for Streptococcus Viridans Bacteremia | Infections and infestations | Non-systematic Assessment |
|
| Hospitalization for Candida Parapsilosis | Infections and infestations | Non-systematic Assessment |
|
| Hospitalized for Septic Shock | Infections and infestations | Non-systematic Assessment |
|
| Hospitalized for Hyperglycemia | Endocrine disorders | Non-systematic Assessment |
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| Hospitalized for Sinusitis | Infections and infestations | Non-systematic Assessment |
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| Hospitalized for Anorexia | Gastrointestinal disorders | Non-systematic Assessment |
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| Hospitalized for Otitis Media | Ear and labyrinth disorders | Non-systematic Assessment |
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| Hospitalized for Renal Insufficiency | Renal and urinary disorders | Non-systematic Assessment |
|
| Hospitalized for C. Difficile | Infections and infestations | Non-systematic Assessment |
|
| Hospitalized for Parainfluenza | Infections and infestations | Non-systematic Assessment |
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| Hospitalization for Respiratory Syncytial Virus | Infections and infestations | Non-systematic Assessment |
|
| Hospitalization for Chicken Pox | Infections and infestations | Non-systematic Assessment |
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| Hospitalization for Staphylococcus aureus | Infections and infestations | Non-systematic Assessment |
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| Hospitalization for CMV Mucositis | Infections and infestations | Non-systematic Assessment |
|
| Hospitalization for Haemophilus influenzae | Infections and infestations | Non-systematic Assessment |
|
| Hospitalization for Staphylococcus epidermidis | Infections and infestations | Non-systematic Assessment |
|
| Hospitalization for Micrococcus bacteremia | Infections and infestations | Non-systematic Assessment |
|
| Hospitalization for Staphylococcus Hickman Site Infection | Infections and infestations | Non-systematic Assessment |
|
| Hospitalization for Hip Replacement | Musculoskeletal and connective tissue disorders | Non-systematic Assessment | First event was total right hip replacement due to AVN steroid use. Second event was total left hip replacement due to AVN steroid use |
|
| Hospitalized for Chylothorax | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Hospitalized for Oliguric Failure | Renal and urinary disorders | Non-systematic Assessment |
|
| Hospitalized for tumor in back (relapse) | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Non-systematic Assessment |
|
| Hospitalized for Pancytopenia | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Anemia | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| Hypertension | Cardiac disorders | Non-systematic Assessment |
|
| Fatigue | General disorders | Non-systematic Assessment |
|
| Diabetic Foot Ulcers | Endocrine disorders | Non-systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Non-systematic Assessment |
|
| Bronchitis | Infections and infestations | Non-systematic Assessment |
|
| Pneumonia | Infections and infestations | Non-systematic Assessment |
|
| C. Difficile | Infections and infestations | Non-systematic Assessment |
|
| Shingles | Infections and infestations | Non-systematic Assessment |
|
| sinusitis | Infections and infestations | Non-systematic Assessment |
|
| Otitis Media | Infections and infestations | Non-systematic Assessment |
|
| Chicken Pox | Infections and infestations | Non-systematic Assessment |
|
| Strep Throat | Infections and infestations | Non-systematic Assessment |
|
| Eye Infection | Eye disorders | Non-systematic Assessment |
|
| Coag Negative Staph | Infections and infestations | Non-systematic Assessment |
|
| Left Parotid Gland Infection | Infections and infestations | Non-systematic Assessment |
|
| Pseudomonas aeruginosa | Infections and infestations | Non-systematic Assessment |
|
| Aspergillus | Infections and infestations | Non-systematic Assessment |
|
| BK Virus | Infections and infestations | Non-systematic Assessment |
|
| Lower Extremity Edema | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Hyperlipidemia | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Osteoporosis | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Depression | Nervous system disorders | Non-systematic Assessment |
|
| Renal Insufficiency | Renal and urinary disorders | Non-systematic Assessment |
|
| Basal and Squamous Cell | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Non-systematic Assessment |
|
| Urinary Bladder Tumor | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Non-systematic Assessment |
|
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| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Proportion of pts with at least 1 fungal inf'n |
|
| Proportion of pts with culture negative sepsis |
|
| Title | Measurements |
|---|---|
|
| Prop'n with subsequent prostate adenocarcinoma |
|
| Prop'n with subsequent renal cell carcinoma |
|
| Proportion with subsequent bladder carcinoma |
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| Prop'n with post-BMT lymphoproliferative disease |
|