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Sirolimus for Autoimmune Disease of Blood Cells

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ClinicalTrials.gov Identifier: NCT00392951
Recruitment Status : Active, not recruiting
First Posted : October 26, 2006
Results First Posted : December 6, 2017
Last Update Posted : November 7, 2018
Sponsor:
Information provided by (Responsible Party):
Children's Hospital of Philadelphia

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Autoimmune Pancytopenia
Autoimmune Lymphoproliferative Syndrome (ALPS)
Evans Syndrome
Idiopathic Thrombocytopenic Purpura
Anemia, Hemolytic, Autoimmune
Autoimmune Neutropenia
Lupus Erythematosus, Systemic
Inflammatory Bowel Disease
Rheumatoid Arthritis
Intervention Drug: sirolimus
Enrollment 30
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Sirolimus Treatment
Hide Arm/Group Description

Sirolimus treatment

sirolimus: Tablet or liquid; taken once or twice daily; dosage is based on establishing a serum trough of 5-15 ng/ml by high-performance liquid chromatography (initial loading dose of 3 mg/m2 then 2.5 mg/m2 with adjustment based on serum trough)

Period Title: Overall Study
Started 30
Completed 30
Not Completed 0
Arm/Group Title Sirolimus Treatment
Hide Arm/Group Description

Sirolimus treatment

sirolimus: Tablet or liquid; taken once or twice daily; dosage is based on establishing a serum trough of 5-15 ng/ml by high-performance liquid chromatography (initial loading dose of 3 mg/m2 then 2.5 mg/m2 with adjustment based on serum trough)

Overall Number of Baseline Participants 30
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
<=18 years
12
  40.0%
Between 18 and 65 years
18
  60.0%
>=65 years
0
   0.0%
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 30 participants
11
(1.8 to 21)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
Female
10
  33.3%
Male
20
  66.7%
Race and Ethnicity Not Collected   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants
[1]
Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 30 participants
30
1.Primary Outcome
Title Number of Participants With Grade 3 and 4 Toxicities of Administration of Oral Sirolimus
Hide Description

Grade 3 toxicities are those that are considered severe or medically equivalent requiring hospitalization or prolonged hospitalization (according to CTCAE criteria 3.0).

Grade 4 toxicities are those that are life-threatening (urgent intervention indicated) (according to CTCAE criteria 3.0).

Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sirolimus Treatment
Hide Arm/Group Description:

Sirolimus treatment

sirolimus: Tablet or liquid; taken once or twice daily; dosage is based on establishing a serum trough of 5-15 ng/ml by high-performance liquid chromatography (initial loading dose of 3 mg/m2 then 2.5 mg/m2 with adjustment based on serum trough)

Overall Number of Participants Analyzed 30
Measure Type: Number
Unit of Measure: participants
1
2.Secondary Outcome
Title Number of Participants With Autoimmune Disease Response to Oral Sirolimus
Hide Description Complete response (CR) is complete resolution in all autoimmune cytopenias (neutropenia, anemia thrombocytopenia) maintained for more than two months, combined with an ability to wean off corticosteroids and/or other immunosuppressive medication. Partial response (PR) is improvement in any cytopenias by at least one grade, lasting more than two months, without worsening any other cytopenias or stable disease with the ability to wean corticosteroids and/or immunosuppressive medications by at least 50%. No response (NR) is no change in cytopenias with treatment, and the inability to wean corticosteroids or other immunosuppressive medications. Progressive disease (PD) refers to obtaining a CR or PR by the 3 month observation and relapsing or progressing by the 6 month observation, leading to cessation of study drug.
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Number analyzed per row reflects number of participants with each condition
Arm/Group Title Sirolimus Treatment
Hide Arm/Group Description:

Sirolimus treatment

sirolimus: Tablet or liquid; taken once or twice daily; dosage is based on establishing a serum trough of 5-15 ng/ml by high-performance liquid chromatography (initial loading dose of 3 mg/m2 then 2.5 mg/m2 with adjustment based on serum trough)

Overall Number of Participants Analyzed 30
Measure Type: Count of Participants
Unit of Measure: Participants
Response in patients w/ ALPS Number Analyzed 12 participants
Complete Response (CR)
11
  91.7%
Partial Response (PR)
1
   8.3%
No Response (NR)
0
   0.0%
Progressive Disease (PD)
0
   0.0%
Response in patients w/ multilineage cytopenias Number Analyzed 12 participants
Complete Response (CR)
7
  58.3%
Partial Response (PR)
1
   8.3%
No Response (NR)
2
  16.7%
Progressive Disease (PD)
2
  16.7%
Resp pts w/ single-lineage autoimmune cytopenias Number Analyzed 6 participants
Complete Response (CR)
1
  16.7%
Partial Response (PR)
2
  33.3%
No Response (NR)
3
  50.0%
Progressive Disease (PD)
0
   0.0%
3.Secondary Outcome
Title Trough Levels Produced by Administration of Oral Sirolimus
Hide Description Pharmacokinetic levels produced by administration of oral sirolimus
Time Frame Within first 5 days of starting sirolimus
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sirolimus Treatment
Hide Arm/Group Description:

Sirolimus treatment

sirolimus: Tablet or liquid; taken once or twice daily; dosage is based on establishing a serum trough of 5-15 ng/ml by high-performance liquid chromatography (initial loading dose of 3 mg/m2 then 2.5 mg/m2 with adjustment based on serum trough)

Overall Number of Participants Analyzed 30
Mean (Full Range)
Unit of Measure: nanograms/dL
8.5
(2.9 to 20)
4.Secondary Outcome
Title Effect of Sirolimus on Intracellular Targets
Hide Description Needs more specific information
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This was an optional assessment- there was no enrollment. Data were not collected.
Arm/Group Title Sirolimus Treatment
Hide Arm/Group Description:

Sirolimus treatment

sirolimus: Tablet or liquid; taken once or twice daily; dosage is based on establishing a serum trough of 5-15 ng/ml by high-performance liquid chromatography (initial loading dose of 3 mg/m2 then 2.5 mg/m2 with adjustment based on serum trough)

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Number of Participants With Lymphoproliferation Response to Oral Sirolimus
Hide Description Complete response (CR) is complete resolution of any lymphadenopathy and splenomegaly for at least two months. Partial response (PR) is a reduction in size of at least 50% of lymphadenopathy or splenomegaly for at least two months. No response (NR) is no change or < 50% reduction in lymphadenopathy or splenomegaly. Progressive Disease (PD) is obtaining a CR or PR by the 3 month observation and relapsing or progressing by the 6 month observation, leading to cessation of study drug. Not Applicable (N/A) is there is no evidence of disease (No pathologic lymphadenopathy or splenomegaly at time of enrollment).
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Number analyzed per row reflects number of participants with each condition
Arm/Group Title Sirolimus Treatment
Hide Arm/Group Description:

Sirolimus treatment

sirolimus: Tablet or liquid; taken once or twice daily; dosage is based on establishing a serum trough of 5-15 ng/ml by high-performance liquid chromatography (initial loading dose of 3 mg/m2 then 2.5 mg/m2 with adjustment based on serum trough)

Overall Number of Participants Analyzed 30
Measure Type: Count of Participants
Unit of Measure: Participants
Response in patients w/ ALPS Number Analyzed 12 participants
Complete Response (CR)
11
  91.7%
Partial Response (PR)
1
   8.3%
No Response (NR)
0
   0.0%
Progressive disease (PD)
0
   0.0%
Not Applicable (N/A)
0
   0.0%
Response in patients w/ multilineage cytopenias Number Analyzed 12 participants
Complete Response (CR)
3
  25.0%
Partial Response (PR)
0
   0.0%
No Response (NR)
1
   8.3%
Progressive disease (PD)
1
   8.3%
Not Applicable (N/A)
7
  58.3%
esp pts w/ single-lineage autoimmune cytopenias Number Analyzed 6 participants
Complete Response (CR)
1
  16.7%
Partial Response (PR)
0
   0.0%
No Response (NR)
0
   0.0%
Progressive disease (PD)
0
   0.0%
Not Applicable (N/A)
5
  83.3%
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Sirolimus Treatment
Hide Arm/Group Description

Sirolimus treatment

sirolimus: Tablet or liquid; taken once or twice daily; dosage is based on establishing a serum trough of 5-15 ng/ml by high-performance liquid chromatography (initial loading dose of 3 mg/m2 then 2.5 mg/m2 with adjustment based on serum trough)

All-Cause Mortality
Sirolimus Treatment
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Sirolimus Treatment
Affected / at Risk (%) # Events
Total   1/30 (3.33%)    
Nervous system disorders   
Vasculitis  [1]  1/30 (3.33%)  1
Indicates events were collected by systematic assessment
[1]
This adverse event was determined not to be related to study treatment.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Sirolimus Treatment
Affected / at Risk (%) # Events
Total   15/30 (50.00%)    
Cardiac disorders   
Elevated triglycerides and cholesterol   2/30 (6.67%)  2
Gastrointestinal disorders   
Mucositis   10/30 (33.33%)  10
Gastro-esophageal reflux disease   1/30 (3.33%)  1
Skin and subcutaneous tissue disorders   
Acne   1/30 (3.33%)  1
Sun sensitivity   1/30 (3.33%)  1
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: David T. Teachey, MD
Organization: Children's Hospital of Philadelphia
Phone: 267-426-5802
Responsible Party: Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT00392951     History of Changes
Other Study ID Numbers: 2006-7-4873
First Submitted: October 24, 2006
First Posted: October 26, 2006
Results First Submitted: June 1, 2017
Results First Posted: December 6, 2017
Last Update Posted: November 7, 2018