Trial Outcomes & Findings for Combination Chemotherapy, Radiation Therapy, and an Autologous Peripheral Blood Stem Cell Transplant in Treating Young Patients With Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System (NCT NCT00653068)

Last Updated: 2024-04-23

Results Overview

Estimated 4-year EFS where EFS is calculated as the time from study enrollment to disease progression, disease relapse, occurrence of a second malignant neoplasm, death from any cause or last follow-up whichever occurs first. Kaplan-Meier method is used for estimation. Patients without an event are censored at last contact.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

70 participants

Primary outcome timeframe

Up to 4 years after study enrollment

Results posted on

2024-04-23

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment Within 2-6 weeks after induction therapy or radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Consolidation therapy followed by stem cell rescue repeats every 28 days for 3 courses (C) and 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks (R), the order of which depends on patient age, in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	70
Overall Study COMPLETED	20
Overall Study NOT COMPLETED	50

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment Within 2-6 weeks after induction therapy or radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Consolidation therapy followed by stem cell rescue repeats every 28 days for 3 courses (C) and 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks (R), the order of which depends on patient age, in the absence of disease progression or unacceptable toxicity.
Overall Study Death	9
Overall Study Lack of Efficacy	34
Overall Study Physician Decision	4
Overall Study Withdrawal by Subject	1
Overall Study Ineligible	2

Baseline Characteristics

Combination Chemotherapy, Radiation Therapy, and an Autologous Peripheral Blood Stem Cell Transplant in Treating Young Patients With Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Stratum I n=58 Participants Infants (\<36 months of age) with tumor histology and immunohistochemical analysis diagnostic of AT/RT.	Stratum II Infants with INI1 mutation only based diagnosis (histology is not consistent with AT/RT).	Stratum III n=12 Participants Older children (greater than 36 months of age) with tumor histology and immunohistochemical analysis diagnostic of AT/RT.	Stratum IV Older children with INI1 mutation only based diagnosis.	Total n=70 Participants Total of all reporting groups
Age, Categorical <=18 years	58 Participants n=5 Participants	—	12 Participants n=5 Participants	—	70 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	—	0 Participants n=5 Participants	—	0 Participants n=21 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	—	0 Participants n=5 Participants	—	0 Participants n=21 Participants
Age, Continuous	1 years n=5 Participants	—	4 years n=5 Participants	—	1 years n=21 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	—	8 Participants n=5 Participants	—	36 Participants n=21 Participants
Sex: Female, Male Male	30 Participants n=5 Participants	—	4 Participants n=5 Participants	—	34 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=5 Participants	—	5 Participants n=5 Participants	—	20 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	39 Participants n=5 Participants	—	7 Participants n=5 Participants	—	46 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	—	0 Participants n=5 Participants	—	4 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	—	0 Participants n=5 Participants	—	1 Participants n=21 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	—	2 Participants n=5 Participants	—	3 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	—	0 Participants n=5 Participants	—	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	—	1 Participants n=5 Participants	—	8 Participants n=21 Participants
Race (NIH/OMB) White	40 Participants n=5 Participants	—	7 Participants n=5 Participants	—	47 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	—	0 Participants n=5 Participants	—	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	9 Participants n=5 Participants	—	2 Participants n=5 Participants	—	11 Participants n=21 Participants
Region of Enrollment Canada	6 Participants n=5 Participants	—	2 Participants n=5 Participants	—	8 Participants n=21 Participants
Region of Enrollment United States	51 Participants n=5 Participants	—	10 Participants n=5 Participants	—	61 Participants n=21 Participants
Region of Enrollment Australia	1 Participants n=5 Participants	—	0 Participants n=5 Participants	—	1 Participants n=21 Participants

PRIMARY outcome

Timeframe: Up to 4 years after study enrollment

Population: One patient was ineligible in stratum I and one patient was ineligible in stratum III. There were no patients enrolled in Stratum 2 or 4.

Outcome measures

Outcome measures
Measure	Stratum I n=57 Participants Infants (\<36 months of age) with tumor histology and immunohistochemical analysis diagnostic of AT/RT.	Stratum III n=11 Participants Older children (greater than 36 months of age) with tumor histology and immunohistochemical analysis diagnostic of AT/RT.
Event-free Survival	0.3401 Estimated probability Interval 0.2174 to 0.4666	0.4500 Estimated probability Interval 0.1267 to 0.7345

PRIMARY outcome

Timeframe: Up to 4 years after study enrollment

Population: One patient was ineligible in stratum I and one patient was ineligible in stratum III. There were no patients enrolled in Stratum 2 or 4.

Estimated 4-year survival, where survival is calculated as the time from study enrollment to death from any cause or last follow-up alive whichever occurs first. Kaplan-Meier method is used for estimation. Patients alive at last contact are censored.

Outcome measures

Outcome measures
Measure	Stratum I n=57 Participants Infants (\<36 months of age) with tumor histology and immunohistochemical analysis diagnostic of AT/RT.	Stratum III n=11 Participants Older children (greater than 36 months of age) with tumor histology and immunohistochemical analysis diagnostic of AT/RT.
Overall Survival (OS)	0.3888 Estimated Probability Interval 0.2582 to 0.5173	0.5486 Estimated Probability Interval 0.1873 to 0.8064

PRIMARY outcome

Timeframe: During and after completion of study treatment up to 1 year after enrollment.

Population: One patient was ineligible in stratum I and one patient was ineligible in stratum III. There were no patients enrolled in Stratum 2 or 4.

The number of patients who experience death that is considered to be primarily attributable to complications of treatment.

Outcome measures

Outcome measures
Measure	Stratum I n=57 Participants Infants (\<36 months of age) with tumor histology and immunohistochemical analysis diagnostic of AT/RT.	Stratum III n=11 Participants Older children (greater than 36 months of age) with tumor histology and immunohistochemical analysis diagnostic of AT/RT.
Toxic Death	3 Participants	1 Participants

SECONDARY outcome

Timeframe: During protocol therapy up to 1 year after enrollment.

Population: 68 eligible patients were evaluable

Number of Participants with Nonhematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy.

Outcome measures

Outcome measures
Measure	Stratum I n=68 Participants Infants (\<36 months of age) with tumor histology and immunohistochemical analysis diagnostic of AT/RT.	Stratum III Older children (greater than 36 months of age) with tumor histology and immunohistochemical analysis diagnostic of AT/RT.
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Acidosis	1 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Acute kidney injury	1 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Apnea	2 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Adult respiratory distress syndrome	1 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Aspiration	3 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Atelectasis	1 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Catheter related infection	2 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Central nervous system necrosis	1 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Dehydration	1 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Diarrhea	1 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Dissmeminated intravascular coagulation (DIC)	1 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Enterocolitis	1 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Febrile neutropenia	6 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Hearing impairment	1 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Hematuria	1 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Hydrocephalus	1 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Hypernatremia	1 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Hypoalbuminemia	1 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Hypocalcemia	3 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Hypoglycemia	2 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Hypokalemia	9 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Hyponatremia	2 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Hypophosphatemia	2 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Hypotension	4 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Hypoxia	6 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Increased Alanine aminotransferase	5 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Increased Aspartate aminotransferase	4 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Increased Lipase	1 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Intracranial hemorrhage	2 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy ntraoperative venous injury	1 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Laryngospasm	1 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Left ventricular systolic dysfunction	1 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Lung infection	3 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Multi-organ failure	1 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Mucositis oral	3 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Poisoning and procedural complications	1 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Other gastrointestinal disorders	1 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Other infection	7 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Pneumonitis	2 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Productive cough	1 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Pulmonary edema	1 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Recurrent laryngeal nerve palsy	1 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Renal calculi	1 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Respiratory failure	3 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Seizure	2 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Sepsis	6 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Sinus tachycardia	2 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Stridor	2 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Upper respiratory infection	1 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Vascular access complication	1 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Voice alteration	1 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Vomiting	1 Participants	—
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy Weight loss	1 Participants	—

Adverse Events

Stratum I

Serious events: 7 serious events

Other events: 43 other events

Deaths: 0 deaths

Stratum III

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Results Reporting Coordinator

Children's Oncology Group

Phone: 626-447-0064

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Must obtain prior Sponsor approval.
Publication restrictions are in place

Restriction type: OTHER

Measure	Stratum I n=57 participants at risk Infants (\<36 months of age) with tumor histology and immunohistochemical analysis diagnostic of AT/RT	Stratum III n=11 participants at risk Older children (greater than 36 months of age) with tumor histology and immunohistochemical analysis diagnostic of AT/RT.
Blood and lymphatic system disorders Disseminated intravascular coagulation	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Cardiac disorders Left ventricular systolic dysfunction	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
General disorders Multi-organ failure	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Infections and infestations Enterocolitis infectious	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Infections and infestations Sepsis	3.5% 2/57 • Number of events 2 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Infections and infestations Upper respiratory infection	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Investigations Lymphocyte count decreased	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Investigations Neutrophil count decreased	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Investigations White blood cell decreased	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Metabolism and nutrition disorders Acidosis	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Metabolism and nutrition disorders Hypoalbuminemia	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Metabolism and nutrition disorders Hypokalemia	3.5% 2/57 • Number of events 2 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Metabolism and nutrition disorders Hypophosphatemia	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Nervous system disorders Central nervous system necrosis	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Nervous system disorders Intracranial hemorrhage	3.5% 2/57 • Number of events 2 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Nervous system disorders Seizure	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Respiratory, thoracic and mediastinal disorders Pulmonary edema	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Respiratory, thoracic and mediastinal disorders Respiratory failure	3.5% 2/57 • Number of events 2 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Vascular disorders Hypotension	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.

Measure	Stratum I n=57 participants at risk Infants (\<36 months of age) with tumor histology and immunohistochemical analysis diagnostic of AT/RT	Stratum III n=11 participants at risk Older children (greater than 36 months of age) with tumor histology and immunohistochemical analysis diagnostic of AT/RT.
Blood and lymphatic system disorders Anemia	10.5% 6/57 • Number of events 6 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Blood and lymphatic system disorders Febrile neutropenia	10.5% 6/57 • Number of events 6 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Cardiac disorders Sinus tachycardia	3.5% 2/57 • Number of events 2 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Ear and labyrinth disorders Hearing impaired	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Gastrointestinal disorders Diarrhea	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Gastrointestinal disorders Mucositis oral	3.5% 2/57 • Number of events 2 There were no patients enrolled in Stratum 2 or 4.	9.1% 1/11 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.
Gastrointestinal disorders Vomiting	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
General disorders Death NOS	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Infections and infestations Catheter related infection	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	9.1% 1/11 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.
Infections and infestations Infections and infestations - Other, specify	12.3% 7/57 • Number of events 7 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Infections and infestations Lung infection	3.5% 2/57 • Number of events 2 There were no patients enrolled in Stratum 2 or 4.	9.1% 1/11 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.
Infections and infestations Sepsis	7.0% 4/57 • Number of events 4 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other, specify	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Injury, poisoning and procedural complications Intraoperative venous injury	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Injury, poisoning and procedural complications Vascular access complication	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Investigations Alanine aminotransferase increased	8.8% 5/57 • Number of events 5 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Investigations Aspartate aminotransferase increased	7.0% 4/57 • Number of events 4 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Investigations Investigations - Other, specify	0.00% 0/57 There were no patients enrolled in Stratum 2 or 4.	9.1% 1/11 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.
Investigations Lipase increased	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Investigations Lymphocyte count decreased	31.6% 18/57 • Number of events 18 There were no patients enrolled in Stratum 2 or 4.	9.1% 1/11 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.
Investigations Neutrophil count decreased	64.9% 37/57 • Number of events 37 There were no patients enrolled in Stratum 2 or 4.	45.5% 5/11 • Number of events 5 There were no patients enrolled in Stratum 2 or 4.
Investigations Platelet count decreased	54.4% 31/57 • Number of events 31 There were no patients enrolled in Stratum 2 or 4.	45.5% 5/11 • Number of events 5 There were no patients enrolled in Stratum 2 or 4.
Investigations Weight loss	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Investigations White blood cell decreased	52.6% 30/57 • Number of events 30 There were no patients enrolled in Stratum 2 or 4.	27.3% 3/11 • Number of events 3 There were no patients enrolled in Stratum 2 or 4.
Metabolism and nutrition disorders Dehydration	0.00% 0/57 There were no patients enrolled in Stratum 2 or 4.	9.1% 1/11 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.
Metabolism and nutrition disorders Hypernatremia	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Metabolism and nutrition disorders Hypocalcemia	3.5% 2/57 • Number of events 2 There were no patients enrolled in Stratum 2 or 4.	9.1% 1/11 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.
Metabolism and nutrition disorders Hypoglycemia	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	9.1% 1/11 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.
Metabolism and nutrition disorders Hypokalemia	10.5% 6/57 • Number of events 6 There were no patients enrolled in Stratum 2 or 4.	9.1% 1/11 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.
Metabolism and nutrition disorders Hyponatremia	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	9.1% 1/11 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.
Metabolism and nutrition disorders Hypophosphatemia	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Nervous system disorders Hydrocephalus	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Nervous system disorders Recurrent laryngeal nerve palsy	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Nervous system disorders Seizure	0.00% 0/57 There were no patients enrolled in Stratum 2 or 4.	9.1% 1/11 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.
Renal and urinary disorders Acute kidney injury	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Renal and urinary disorders Hematuria	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Renal and urinary disorders Renal calculi	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Respiratory, thoracic and mediastinal disorders Adult respiratory distress syndrome	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Respiratory, thoracic and mediastinal disorders Apnea	3.5% 2/57 • Number of events 2 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Respiratory, thoracic and mediastinal disorders Aspiration	5.3% 3/57 • Number of events 3 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Respiratory, thoracic and mediastinal disorders Atelectasis	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Respiratory, thoracic and mediastinal disorders Hypoxia	7.0% 4/57 • Number of events 4 There were no patients enrolled in Stratum 2 or 4.	9.1% 1/11 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.
Respiratory, thoracic and mediastinal disorders Laryngospasm	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	9.1% 1/11 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.
Respiratory, thoracic and mediastinal disorders Productive cough	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Respiratory, thoracic and mediastinal disorders Stridor	3.5% 2/57 • Number of events 2 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Respiratory, thoracic and mediastinal disorders Voice alteration	1.8% 1/57 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.	0.00% 0/11 There were no patients enrolled in Stratum 2 or 4.
Vascular disorders Hypotension	3.5% 2/57 • Number of events 2 There were no patients enrolled in Stratum 2 or 4.	9.1% 1/11 • Number of events 1 There were no patients enrolled in Stratum 2 or 4.