Trial Outcomes & Findings for Sirolimus in Previously Treated Idiopathic Multicentric Castleman Disease (NCT NCT03933904)

Last Updated: 2025-08-08

Results Overview

Clinical Benefit Response (CBR): The CBR was defined by improvements in clinical symptoms such as fatigue, anorexia, fever, and night sweats.6 Laboratory markers such as hemoglobin levels and weight change were also included in the CBR criteria (Table 1). A CBR was considered positive if there was at least a 25% reduction in the size of the largest lymph node (measured by modified Cheson criteria), a significant improvement in at least one laboratory marker (e.g., hemoglobin), and improvement in at least one clinical symptom without worsening of others.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

7 participants

Primary outcome timeframe

12 ± 1 months

Results posted on

2025-08-08

Participant Flow

Recruitment started 9/25/2019 and continued until 6/30/2024. Potential participants were informed about the study through various channels, including communication and fliers from licensed site investigators during routine clinical visits. Individuals who previously consented to be contacted for future research were reached by email or phone. Additional outreach was conducted through tools like Epic as well as through the Castleman Disease Collaborative Network (CDCN).

Before assignment, participants underwent several steps to confirm eligibility. This included a washout period from any systemic therapies used to treat iMCD, as well as various laboratory tests to ensure they were healthy enough to participate and did not have any uncontrolled infections or conditions that could mimic iMCD.

Participant milestones

Participant milestones
Measure	Sirolimus For adults, the treatment began with a loading dose of 5 mg/m² on Day 1, designed to quickly achieve therapeutic levels of sirolimus. This loading dose was rounded to the nearest milligram and could be adjusted at the discretion of the prescribing physician based on individual tolerability and clinical judgment.
Overall Study STARTED	7
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Sirolimus in Previously Treated Idiopathic Multicentric Castleman Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sirolimus n=7 Participants Oral sirolimus: Loading dose of 5 mg/m\^2, rounded to the nearest mg, on day 1. Starting on day 2, oral sirolimus daily at 2.5 mg/m\^2/day (rounded to the nearest mg), target trough level 10-15 ng/mL by HPLC, for 12 months.
Age, Continuous	57 years n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	7 Participants n=5 Participants
Histopathological Subtype Hypervascular/Hyaline Vascular	1 Participants n=5 Participants
Histopathological Subtype Mixed	3 Participants n=5 Participants
Histopathological Subtype Plasmacytic	1 Participants n=5 Participants
Histopathological Subtype Indeterminate	2 Participants n=5 Participants
Clinical Subtype Thrombocytopenia, Anasarca, Fever, Reticulin fibrosis, and Organomegaly (TAFRO) Subtype	2 Participants n=5 Participants
Clinical Subtype Idiopathic Plasmacytic Lymphadenopathy (IPL) Subtype	2 Participants n=5 Participants
Clinical Subtype Not Otherwise Specified (NOS) Subtype	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 ± 1 months

Outcome measures

Outcome measures
Measure	Sirolimus n=4 Participants Oral sirolimus: For adults, loading dose of 5 mg/m\^2, rounded to the nearest mg, on day 1. For adults, starting on day 2, oral sirolimus daily at 2.5 mg/m\^2/day (rounded to the nearest mg), target trough level 10-15 ng/mL by HPLC, for 12 months. Sirolimus: Sirolimus (also known as rapamycin) inhibits the mTOR protein kinase and is approved by the USA FDA for the prevention of allograft rejection in renal transplant patients ≥ 13 years of age and for the treatment of lymphangioleiomyomatosis.
Percentage of Patients Achieving a Positive Clinical Benefit Response (CBR) Achieved CBR	2 Participants
Percentage of Patients Achieving a Positive Clinical Benefit Response (CBR) Did Not Achieve CBR	2 Participants

SECONDARY outcome

Timeframe: Month 3

Outcome measures

Outcome measures
Measure	Sirolimus n=4 Participants Oral sirolimus: For adults, loading dose of 5 mg/m\^2, rounded to the nearest mg, on day 1. For adults, starting on day 2, oral sirolimus daily at 2.5 mg/m\^2/day (rounded to the nearest mg), target trough level 10-15 ng/mL by HPLC, for 12 months. Sirolimus: Sirolimus (also known as rapamycin) inhibits the mTOR protein kinase and is approved by the USA FDA for the prevention of allograft rejection in renal transplant patients ≥ 13 years of age and for the treatment of lymphangioleiomyomatosis.
Percentage of Patients Achieving a Positive Clinical Benefit Response (CBR) Month 3	1 Participants

SECONDARY outcome

Timeframe: Month 6

Outcome measures

Outcome measures
Measure	Sirolimus n=4 Participants Oral sirolimus: For adults, loading dose of 5 mg/m\^2, rounded to the nearest mg, on day 1. For adults, starting on day 2, oral sirolimus daily at 2.5 mg/m\^2/day (rounded to the nearest mg), target trough level 10-15 ng/mL by HPLC, for 12 months. Sirolimus: Sirolimus (also known as rapamycin) inhibits the mTOR protein kinase and is approved by the USA FDA for the prevention of allograft rejection in renal transplant patients ≥ 13 years of age and for the treatment of lymphangioleiomyomatosis.
Percentage of Patients Achieving a Positive Clinical Benefit Response (CBR) Month 6	2 Participants

SECONDARY outcome

Timeframe: Month 9

Outcome measures

Outcome measures
Measure	Sirolimus n=4 Participants Oral sirolimus: For adults, loading dose of 5 mg/m\^2, rounded to the nearest mg, on day 1. For adults, starting on day 2, oral sirolimus daily at 2.5 mg/m\^2/day (rounded to the nearest mg), target trough level 10-15 ng/mL by HPLC, for 12 months. Sirolimus: Sirolimus (also known as rapamycin) inhibits the mTOR protein kinase and is approved by the USA FDA for the prevention of allograft rejection in renal transplant patients ≥ 13 years of age and for the treatment of lymphangioleiomyomatosis.
Percentage of Patients Achieving a Positive Clinical Benefit Response (CBR) Month 9	2 Participants

SECONDARY outcome

Timeframe: Up to 73 weeks

Outcome measures

Outcome measures
Measure	Sirolimus n=7 Participants Oral sirolimus: For adults, loading dose of 5 mg/m\^2, rounded to the nearest mg, on day 1. For adults, starting on day 2, oral sirolimus daily at 2.5 mg/m\^2/day (rounded to the nearest mg), target trough level 10-15 ng/mL by HPLC, for 12 months. Sirolimus: Sirolimus (also known as rapamycin) inhibits the mTOR protein kinase and is approved by the USA FDA for the prevention of allograft rejection in renal transplant patients ≥ 13 years of age and for the treatment of lymphangioleiomyomatosis.
Percentage of Patients That Remain on Study Drug for the Duration of the Study	4 Participants

SECONDARY outcome

Timeframe: Up to 73 weeks

Outcome measures

Outcome measures
Measure	Sirolimus n=7 Participants Oral sirolimus: For adults, loading dose of 5 mg/m\^2, rounded to the nearest mg, on day 1. For adults, starting on day 2, oral sirolimus daily at 2.5 mg/m\^2/day (rounded to the nearest mg), target trough level 10-15 ng/mL by HPLC, for 12 months. Sirolimus: Sirolimus (also known as rapamycin) inhibits the mTOR protein kinase and is approved by the USA FDA for the prevention of allograft rejection in renal transplant patients ≥ 13 years of age and for the treatment of lymphangioleiomyomatosis.
Percentage of Patients That Indicate That They Are Currently Receiving Sirolimus at the End of the Follow Up Phase	1 Participants

SECONDARY outcome

Timeframe: 12 months ± 2 weeks

The CHAP scale consists of C-reactive protein (CRP), hemoglobin, albumin, and Eastern Cooperative Oncology Group (ECOG) performance score, each with a subscale range of 0-4. Each criterion in the CHAP scoring system provides a graded measure for a patient's disease activity. The sum of the four scores provides an objective scale for measuring a patient's disease activity and monitoring how it changes over time (scale range 0-16). A higher score indicates greater disease activity.

Outcome measures

Outcome measures
Measure	Sirolimus n=4 Participants Oral sirolimus: For adults, loading dose of 5 mg/m\^2, rounded to the nearest mg, on day 1. For adults, starting on day 2, oral sirolimus daily at 2.5 mg/m\^2/day (rounded to the nearest mg), target trough level 10-15 ng/mL by HPLC, for 12 months. Sirolimus: Sirolimus (also known as rapamycin) inhibits the mTOR protein kinase and is approved by the USA FDA for the prevention of allograft rejection in renal transplant patients ≥ 13 years of age and for the treatment of lymphangioleiomyomatosis.
Disease Activity, as Measured by the CHAP Scale	3 score on a scale Standard Deviation 0.433

SECONDARY outcome

Timeframe: Month 12

MCD-related Overall Symptom Score is measured by 34 MCD-related outcome measures. These scores addressed fatigue, weight change, night sweats, etc. The scores were evaluated and graded (as per CTCAE version 4.0, May, 2009), which was used to assess the efficacy of the study intervention. Each symptom score was measured on a numeric scale, ranging from 1 (no symptom) to 5 (very severe or disabling). Scores were combined to create a combined score per patient at each time point. Patients were then assessed as having no response, a symptomatic response, or a durable symptomatic response. A symptomatic response was defined as a ≥50% decrease in the 34-point symptom score, a durable symptomatic response is a ≥50% decrease in the 34-point symptom score from baseline that was maintained for a minimum of 18 weeks.

Outcome measures

Outcome measures
Measure	Sirolimus n=4 Participants Oral sirolimus: For adults, loading dose of 5 mg/m\^2, rounded to the nearest mg, on day 1. For adults, starting on day 2, oral sirolimus daily at 2.5 mg/m\^2/day (rounded to the nearest mg), target trough level 10-15 ng/mL by HPLC, for 12 months. Sirolimus: Sirolimus (also known as rapamycin) inhibits the mTOR protein kinase and is approved by the USA FDA for the prevention of allograft rejection in renal transplant patients ≥ 13 years of age and for the treatment of lymphangioleiomyomatosis.
Disease Activity, as Measured by the MCD-related Overall Symptom Score Achieved a Symptomatic Response	1 Participants
Disease Activity, as Measured by the MCD-related Overall Symptom Score Achieved a Durable Symptomatic Response	1 Participants
Disease Activity, as Measured by the MCD-related Overall Symptom Score No Response	2 Participants

SECONDARY outcome

Timeframe: Month 12

Radiological response was assessed using the modified Cheson criteria, which quantify changes in lymph node size. A lymph node response was defined as a 25% reduction in bi-dimensional measurements of the largest lymph node compared to baseline. Patients were then assessed according to the following responses: Complete Response: All index lesion(s) must have regressed to normal size (≤1.0 cm in their greatest transverse diameter. No new sites of lymphadenopathy \>1.5 cm in longest dimension. Partial Response: ≥50% decrease in sum of the products of the greatest diameters (SPD) of index lesion(s), and no new sites of lymphadenopathy \>1.5 cm in longest dimension. Stable Disease: Failure to achieve a CR or PR (see above) without evidence of progressive disease. Progressive Disease: ≥50% increase from nadir in the SPD of any index lesion, or appearance of any new sites of lymphadenopathy that measure \>1.5 cm in longest dimension during or at the end of therapy.

Outcome measures

Outcome measures
Measure	Sirolimus n=4 Participants Oral sirolimus: For adults, loading dose of 5 mg/m\^2, rounded to the nearest mg, on day 1. For adults, starting on day 2, oral sirolimus daily at 2.5 mg/m\^2/day (rounded to the nearest mg), target trough level 10-15 ng/mL by HPLC, for 12 months. Sirolimus: Sirolimus (also known as rapamycin) inhibits the mTOR protein kinase and is approved by the USA FDA for the prevention of allograft rejection in renal transplant patients ≥ 13 years of age and for the treatment of lymphangioleiomyomatosis.
Proportion of Patients Achieving a Lymph Node Response, Following the Modified Cheson Response Criteria Achieved Complete Response	1 participants
Proportion of Patients Achieving a Lymph Node Response, Following the Modified Cheson Response Criteria Progressive Disease	2 participants
Proportion of Patients Achieving a Lymph Node Response, Following the Modified Cheson Response Criteria Stable Disease	1 participants

Adverse Events

Sirolimus

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sirolimus n=7 participants at risk For adults, the treatment began with a loading dose of 5 mg/m² on Day 1, designed to quickly achieve therapeutic levels of sirolimus. This loading dose was rounded to the nearest milligram and could be adjusted at the discretion of the prescribing physician based on individual tolerability and clinical judgment.
Infections and infestations Pneumonia	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Infections and infestations Sepsis	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.

Other adverse events

Other adverse events
Measure	Sirolimus n=7 participants at risk For adults, the treatment began with a loading dose of 5 mg/m² on Day 1, designed to quickly achieve therapeutic levels of sirolimus. This loading dose was rounded to the nearest milligram and could be adjusted at the discretion of the prescribing physician based on individual tolerability and clinical judgment.
Skin and subcutaneous tissue disorders Pruritus	28.6% 2/7 • Number of events 3 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Gastrointestinal disorders Abdominal pain	28.6% 2/7 • Number of events 2 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Hepatobiliary disorders Bile duct stenosis	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Blood and lymphatic system disorders Blood and lymphatic system disorders-Other, specify	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Respiratory, thoracic and mediastinal disorders Cough	28.6% 2/7 • Number of events 2 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Eye disorders Conjunctivitis	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Infections and infestations Covid-19 Infection	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Gastrointestinal disorders Diarrhea	28.6% 2/7 • Number of events 2 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Gastrointestinal disorders Dysphagia	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Respiratory, thoracic and mediastinal disorders Dyspnea	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Eye disorders Eye pain	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Nervous system disorders Headache	42.9% 3/7 • Number of events 3 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Skin and subcutaneous tissue disorders Hyperhidrosis	28.6% 2/7 • Number of events 2 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Skin and subcutaneous tissue disorders Itchy on palms	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Infections and infestations Lung infection	14.3% 1/7 • Number of events 2 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Musculoskeletal and connective tissue disorders Muscle cramp	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Gastrointestinal disorders Nausea	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Musculoskeletal and connective tissue disorders Neck pain	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Nervous system disorders Neuropathy	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Nervous system disorders Peripheral sensory neuropathy	14.3% 1/7 • Number of events 2 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Respiratory, thoracic and mediastinal disorders Pleural effusion	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Skin and subcutaneous tissue disorders Rash acneiform	14.3% 1/7 • Number of events 2 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Respiratory, thoracic and mediastinal disorders Shortness of breath	28.6% 2/7 • Number of events 2 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Respiratory, thoracic and mediastinal disorders Sore throat	28.6% 2/7 • Number of events 2 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Nervous system disorders Tremors	28.6% 2/7 • Number of events 2 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Infections and infestations Urinary Tract Infection	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify (ankle)	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify (groin)	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify (torso)	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Musculoskeletal and connective tissue disorders Lump on knee	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Gastrointestinal disorders Gastrointestinal disorders - Other (tongue ulcer)	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Gastrointestinal disorders Mucositis oral (mouth sores)	28.6% 2/7 • Number of events 2 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Nervous system disorders Generalized muscle weakness (worsening)	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
General disorders Fever	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
General disorders Fatigue	57.1% 4/7 • Number of events 4 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Respiratory, thoracic and mediastinal disorders Epistaxis	14.3% 1/7 • Number of events 2 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Respiratory, thoracic and mediastinal disorders Dry cough (worsening)	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
General disorders Chills	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Musculoskeletal and connective tissue disorders Arthralgia	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Gastrointestinal disorders Ascites (worsening)	28.6% 2/7 • Number of events 2 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Vascular disorders Edema limb (leg swelling)	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Gastrointestinal disorders Lip pain	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Metabolism and nutrition disorders Hypertriglyceridemia	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Vascular disorders Swelling of hands and feet (Edema limbs)	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Vascular disorders Vascular disorders - Other	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Skin and subcutaneous tissue disorders Worsening of night sweats	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Skin and subcutaneous tissue disorders Worsening of rash	14.3% 1/7 • Number of events 1 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.
Musculoskeletal and connective tissue disorders Pain (whole body)	42.9% 3/7 • Number of events 3 • Adverse events were collected from baseline to study completion (up to 73 weeks). Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.

Additional Information

Dr. David Fajgenbaum

Center for Cytokine Storm Treatment & Laboratory (CSTL), University of Pennsylvania

Phone: 215-614-0935

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60