Trial Outcomes & Findings for Sirolimus for Autoimmune Disease of Blood Cells (NCT NCT00392951)
NCT ID: NCT00392951
Last Updated: 2019-11-19
Results Overview
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).
COMPLETED
PHASE1/PHASE2
30 participants
6 months
2019-11-19
Participant Flow
Participant milestones
| Measure |
Sirolimus Treatment
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 Study
STARTED
|
30
|
|
Overall Study
COMPLETED
|
30
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Sirolimus Treatment
n=30 Participants
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)
|
|---|---|
|
Age, Categorical
<=18 years
|
12 Participants
n=30 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
18 Participants
n=30 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=30 Participants
|
|
Age, Continuous
|
11 years
n=30 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=30 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=30 Participants
|
|
Region of Enrollment
United States
|
30 Participants
n=30 Participants
|
PRIMARY outcome
Timeframe: 6 monthsGrade 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).
Outcome measures
| Measure |
Sirolimus Treatment
n=30 Participants
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)
|
|---|---|
|
Number of Participants With Grade 3 and 4 Toxicities of Administration of Oral Sirolimus
|
1 participants
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: Number analyzed per row reflects number of participants with each condition
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.
Outcome measures
| Measure |
Sirolimus Treatment
n=30 Participants
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)
|
|---|---|
|
Number of Participants With Autoimmune Disease Response to Oral Sirolimus
Response in patients w/ multilineage cytopenias · Progressive Disease (PD)
|
2 Participants
|
|
Number of Participants With Autoimmune Disease Response to Oral Sirolimus
Response in patients w/ ALPS · Complete Response (CR)
|
11 Participants
|
|
Number of Participants With Autoimmune Disease Response to Oral Sirolimus
Response in patients w/ ALPS · Partial Response (PR)
|
1 Participants
|
|
Number of Participants With Autoimmune Disease Response to Oral Sirolimus
Response in patients w/ ALPS · No Response (NR)
|
0 Participants
|
|
Number of Participants With Autoimmune Disease Response to Oral Sirolimus
Response in patients w/ ALPS · Progressive Disease (PD)
|
0 Participants
|
|
Number of Participants With Autoimmune Disease Response to Oral Sirolimus
Response in patients w/ multilineage cytopenias · Complete Response (CR)
|
7 Participants
|
|
Number of Participants With Autoimmune Disease Response to Oral Sirolimus
Response in patients w/ multilineage cytopenias · Partial Response (PR)
|
1 Participants
|
|
Number of Participants With Autoimmune Disease Response to Oral Sirolimus
Response in patients w/ multilineage cytopenias · No Response (NR)
|
2 Participants
|
|
Number of Participants With Autoimmune Disease Response to Oral Sirolimus
Resp pts w/ single-lineage autoimmune cytopenias · Complete Response (CR)
|
1 Participants
|
|
Number of Participants With Autoimmune Disease Response to Oral Sirolimus
Resp pts w/ single-lineage autoimmune cytopenias · Partial Response (PR)
|
2 Participants
|
|
Number of Participants With Autoimmune Disease Response to Oral Sirolimus
Resp pts w/ single-lineage autoimmune cytopenias · No Response (NR)
|
3 Participants
|
|
Number of Participants With Autoimmune Disease Response to Oral Sirolimus
Resp pts w/ single-lineage autoimmune cytopenias · Progressive Disease (PD)
|
0 Participants
|
SECONDARY outcome
Timeframe: Within first 5 days of starting sirolimusPharmacokinetic levels produced by administration of oral sirolimus
Outcome measures
| Measure |
Sirolimus Treatment
n=30 Participants
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)
|
|---|---|
|
Trough Levels Produced by Administration of Oral Sirolimus
|
8.5 nanograms/dL
Interval 2.9 to 20.0
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: This was an optional assessment- there was no enrollment. Data were not collected.
Needs more specific information
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 6 monthsPopulation: Number analyzed per row reflects number of participants with each condition
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).
Outcome measures
| Measure |
Sirolimus Treatment
n=30 Participants
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)
|
|---|---|
|
Number of Participants With Lymphoproliferation Response to Oral Sirolimus
Response in patients w/ ALPS · Complete Response (CR)
|
11 Participants
|
|
Number of Participants With Lymphoproliferation Response to Oral Sirolimus
Response in patients w/ ALPS · Partial Response (PR)
|
1 Participants
|
|
Number of Participants With Lymphoproliferation Response to Oral Sirolimus
Response in patients w/ ALPS · No Response (NR)
|
0 Participants
|
|
Number of Participants With Lymphoproliferation Response to Oral Sirolimus
Response in patients w/ ALPS · Progressive disease (PD)
|
0 Participants
|
|
Number of Participants With Lymphoproliferation Response to Oral Sirolimus
Response in patients w/ ALPS · Not Applicable (N/A)
|
0 Participants
|
|
Number of Participants With Lymphoproliferation Response to Oral Sirolimus
Response in patients w/ multilineage cytopenias · Complete Response (CR)
|
3 Participants
|
|
Number of Participants With Lymphoproliferation Response to Oral Sirolimus
Response in patients w/ multilineage cytopenias · Partial Response (PR)
|
0 Participants
|
|
Number of Participants With Lymphoproliferation Response to Oral Sirolimus
Response in patients w/ multilineage cytopenias · No Response (NR)
|
1 Participants
|
|
Number of Participants With Lymphoproliferation Response to Oral Sirolimus
Response in patients w/ multilineage cytopenias · Progressive disease (PD)
|
1 Participants
|
|
Number of Participants With Lymphoproliferation Response to Oral Sirolimus
Response in patients w/ multilineage cytopenias · Not Applicable (N/A)
|
7 Participants
|
|
Number of Participants With Lymphoproliferation Response to Oral Sirolimus
esp pts w/ single-lineage autoimmune cytopenias · Complete Response (CR)
|
1 Participants
|
|
Number of Participants With Lymphoproliferation Response to Oral Sirolimus
esp pts w/ single-lineage autoimmune cytopenias · Partial Response (PR)
|
0 Participants
|
|
Number of Participants With Lymphoproliferation Response to Oral Sirolimus
esp pts w/ single-lineage autoimmune cytopenias · No Response (NR)
|
0 Participants
|
|
Number of Participants With Lymphoproliferation Response to Oral Sirolimus
esp pts w/ single-lineage autoimmune cytopenias · Progressive disease (PD)
|
0 Participants
|
|
Number of Participants With Lymphoproliferation Response to Oral Sirolimus
esp pts w/ single-lineage autoimmune cytopenias · Not Applicable (N/A)
|
5 Participants
|
Adverse Events
Sirolimus Treatment
Serious adverse events
| Measure |
Sirolimus Treatment
n=30 participants at risk
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)
|
|---|---|
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Nervous system disorders
Vasculitis
|
3.3%
1/30 • Number of events 1
|
Other adverse events
| Measure |
Sirolimus Treatment
n=30 participants at risk
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)
|
|---|---|
|
Gastrointestinal disorders
Mucositis
|
33.3%
10/30 • Number of events 10
|
|
Cardiac disorders
Elevated triglycerides and cholesterol
|
6.7%
2/30 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Acne
|
3.3%
1/30 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Sun sensitivity
|
3.3%
1/30 • Number of events 1
|
|
Gastrointestinal disorders
Gastro-esophageal reflux disease
|
3.3%
1/30 • Number of events 1
|
Additional Information
David T. Teachey, MD
Children's Hospital of Philadelphia
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place