Trial Outcomes & Findings for Dasatinib and Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia (NCT NCT00720109)

NCT ID: NCT00720109

Last Updated: 2020-04-13

Results Overview

Event-Free Survival (EFS) curves will be constructed using the Kaplan-Meier life table method with standard errors computed using the method of Peto and Peto. A 1-sided 95% confidence interval for EFS will be constructed.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

63 participants

Primary outcome timeframe

At 3 years

Results posted on

2020-04-13

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy) See Detailed Description Asparaginase: Given IT Cyclophosphamide: Given IV Cytarabine: Given IT or IV Dasatinib: Given PO Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Hydrocortisone Sodium Succinate: Given IT Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV or PO Mercaptopurine: Given PO Methotrexate: Given IT, PO, or IV Methylprednisolone: Given IV Pegaspargase: Given IM Prednisone: Given PO or IV Radiation Therapy: Some patients undergo cranial RT Vincristine Sulfate: Given IV	Standard-risk Based on Minimal Residual Disease, less than 1%.	High-risk Based on Minimal Residual Disease, great than or equal to 1%.
Induction Period STARTED	63	0	0
Induction Period COMPLETED	57	0	0
Induction Period NOT COMPLETED	6	0	0
Risk Stratification Period STARTED	0	48	9
Risk Stratification Period COMPLETED	0	33	1
Risk Stratification Period NOT COMPLETED	0	15	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy) See Detailed Description Asparaginase: Given IT Cyclophosphamide: Given IV Cytarabine: Given IT or IV Dasatinib: Given PO Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Hydrocortisone Sodium Succinate: Given IT Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV or PO Mercaptopurine: Given PO Methotrexate: Given IT, PO, or IV Methylprednisolone: Given IV Pegaspargase: Given IM Prednisone: Given PO or IV Radiation Therapy: Some patients undergo cranial RT Vincristine Sulfate: Given IV	Standard-risk Based on Minimal Residual Disease, less than 1%.	High-risk Based on Minimal Residual Disease, great than or equal to 1%.
Induction Period Did not meet eligibility criteria	3	0	0
Induction Period Bone Marrow Transplant	2	0	0
Induction Period Physician Decision	1	0	0
Risk Stratification Period Adverse Event	0	1	0
Risk Stratification Period Physician Decision	0	2	1
Risk Stratification Period Bone marrow transplant	0	9	7
Risk Stratification Period Disease progression or relapse	0	2	0
Risk Stratification Period Development of second malignant neoplasm	0	1	0

Baseline Characteristics

Dasatinib and Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy) n=63 Participants See Detailed Description Asparaginase: Given IT Cyclophosphamide: Given IV Cytarabine: Given IT or IV Dasatinib: Given PO Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Hydrocortisone Sodium Succinate: Given IT Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV or PO Mercaptopurine: Given PO Methotrexate: Given IT, PO, or IV Methylprednisolone: Given IV Pegaspargase: Given IM Prednisone: Given PO or IV Radiation Therapy: Some patients undergo cranial RT Vincristine Sulfate: Given IV
Age, Categorical <=18 years	56 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=93 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants
Sex: Female, Male Female	20 Participants n=93 Participants
Sex: Female, Male Male	43 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	52 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=93 Participants
Race (NIH/OMB) Asian	3 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=93 Participants
Race (NIH/OMB) Black or African American	9 Participants n=93 Participants
Race (NIH/OMB) White	45 Participants n=93 Participants
Race (NIH/OMB) More than one race	3 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants

PRIMARY outcome

Timeframe: At 3 years

Population: Patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL).

Outcome measures

Outcome measures
Measure	Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy) n=60 Participants See Detailed Description Asparaginase: Given IT Cyclophosphamide: Given IV Cytarabine: Given IT or IV Dasatinib: Given PO Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Hydrocortisone Sodium Succinate: Given IT Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV or PO Mercaptopurine: Given PO Methotrexate: Given IT, PO, or IV Methylprednisolone: Given IV Pegaspargase: Given IM Prednisone: Given PO or IV Radiation Therapy: Some patients undergo cranial RT Vincristine Sulfate: Given IV	Standard-risk n=48 Participants Based on Minimal Residual Disease, less than 1%.	High-risk n=9 Participants Based on Minimal Residual Disease, great than or equal to 1%.
Event-Free Survival (EFS) of Patients With Standard-risk Disease Treated With Dasatinib in Combination With Intensified Chemotherapy	79.8 Percent probability Interval 71.1 to 88.5	83.2 Percent probability Interval 74.1 to 92.2	66.7 Percent probability Interval 40.9 to 92.5

PRIMARY outcome

Timeframe: Weeks 3 through 23 of treatment (From week 3 Induction through Intensification Block 1)

Population: Patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL)

Number of patients in safety cohort with dose limiting toxicity (DLT)(including treatment delay)

Outcome measures

Outcome measures
Measure	Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy) n=12 Participants See Detailed Description Asparaginase: Given IT Cyclophosphamide: Given IV Cytarabine: Given IT or IV Dasatinib: Given PO Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Hydrocortisone Sodium Succinate: Given IT Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV or PO Mercaptopurine: Given PO Methotrexate: Given IT, PO, or IV Methylprednisolone: Given IV Pegaspargase: Given IM Prednisone: Given PO or IV Radiation Therapy: Some patients undergo cranial RT Vincristine Sulfate: Given IV	Standard-risk Based on Minimal Residual Disease, less than 1%.	High-risk Based on Minimal Residual Disease, great than or equal to 1%.
Feasibility and Toxicity of an Intensified Chemotherapeutic Regimen Incorporating Dasatinib for Treatment of Children and Adolescents With Ph+ ALL Assessed by Examining Adverse Events	1 Pts with DLTs	—	—

SECONDARY outcome

Timeframe: At the end of induction therapy (at 5 weeks)

Population: Patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL).

Percent of patients MRD Positive (MRD \> 0.01%) at End of Induction.

Outcome measures

Outcome measures
Measure	Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy) n=59 Participants See Detailed Description Asparaginase: Given IT Cyclophosphamide: Given IV Cytarabine: Given IT or IV Dasatinib: Given PO Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Hydrocortisone Sodium Succinate: Given IT Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV or PO Mercaptopurine: Given PO Methotrexate: Given IT, PO, or IV Methylprednisolone: Given IV Pegaspargase: Given IM Prednisone: Given PO or IV Radiation Therapy: Some patients undergo cranial RT Vincristine Sulfate: Given IV	Standard-risk n=48 Participants Based on Minimal Residual Disease, less than 1%.	High-risk n=9 Participants Based on Minimal Residual Disease, great than or equal to 1%.
Contribution of Dasatinib on Minimal Residual Disease (MRD) After Induction Therapy	40.7 Percentage of participants Interval 30.8 to 51.4	29.2 Percentage of participants Interval 19.7 to 40.9	100.0 Percentage of participants Interval 73.1 to 100.0

SECONDARY outcome

Timeframe: At end of consolidation (at 11 weeks)

Population: Patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL).

A 1-sample Z-test of proportions (alpha=5%, 1-sided test) will be used.

Outcome measures

Outcome measures
Measure	Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy) n=57 Participants See Detailed Description Asparaginase: Given IT Cyclophosphamide: Given IV Cytarabine: Given IT or IV Dasatinib: Given PO Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Hydrocortisone Sodium Succinate: Given IT Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV or PO Mercaptopurine: Given PO Methotrexate: Given IT, PO, or IV Methylprednisolone: Given IV Pegaspargase: Given IM Prednisone: Given PO or IV Radiation Therapy: Some patients undergo cranial RT Vincristine Sulfate: Given IV	Standard-risk n=48 Participants Based on Minimal Residual Disease, less than 1%.	High-risk n=9 Participants Based on Minimal Residual Disease, great than or equal to 1%.
Percent of Patients MRD Positive (MRD > 0.01%) at End of Consolidation	10.5 Percentage of participants Interval 5.3 to 19.3	0 Percentage of participants Interval 0.0 to 6.4	66.7 Percentage of participants Interval 39.6 to 96.1

SECONDARY outcome

Timeframe: From the time entry on study to first event or date of last follow-up, assessed up to 7 years

Population: Included in the analysis are two patients who received the drug therapy but were not risk classified.

An event is defined as: Induction failure, relapse at any site, secondary malignancy, or death.

Outcome measures

Outcome measures
Measure	Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy) n=60 Participants See Detailed Description Asparaginase: Given IT Cyclophosphamide: Given IV Cytarabine: Given IT or IV Dasatinib: Given PO Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Hydrocortisone Sodium Succinate: Given IT Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV or PO Mercaptopurine: Given PO Methotrexate: Given IT, PO, or IV Methylprednisolone: Given IV Pegaspargase: Given IM Prednisone: Given PO or IV Radiation Therapy: Some patients undergo cranial RT Vincristine Sulfate: Given IV	Standard-risk n=48 Participants Based on Minimal Residual Disease, less than 1%.	High-risk n=9 Participants Based on Minimal Residual Disease, great than or equal to 1%.
Overall EFS Rate for the Combined Cohort of Standard- and High-Risk Patients (Who Receive the Final Chosen Dose of Dasatinib)	79.8 percentage of patients Interval 71.1 to 88.5	83.2 percentage of patients Interval 74.1 to 92.2	66.7 percentage of patients Interval 40.9 to 92.5

Adverse Events

Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy)

Serious events: 36 serious events

Other events: 59 other events

Deaths: 0 deaths

Standard-risk

Serious events: 28 serious events

Other events: 48 other events

Deaths: 0 deaths

High-risk

Serious events: 7 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: 626-241-1546

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy) n=60 participants at risk See Detailed Description Asparaginase: Given IT Cyclophosphamide: Given IV Cytarabine: Given IT or IV Dasatinib: Given PO Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Hydrocortisone Sodium Succinate: Given IT Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV or PO Mercaptopurine: Given PO Methotrexate: Given IT, PO, or IV Methylprednisolone: Given IV Pegaspargase: Given IM Prednisone: Given PO or IV Radiation Therapy: Some patients undergo cranial RT Vincristine Sulfate: Given IV	Standard-risk n=48 participants at risk Based on Minimal Residual Disease, less than 1%.	High-risk n=9 participants at risk Based on Minimal Residual Disease, great than or equal to 1%.
Renal and urinary disorders Renal and urinary disorders - Other, specify	1.7% 1/60 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Nervous system disorders Seizure	3.3% 2/60 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	4.2% 2/48 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Infections and infestations Sepsis	3.3% 2/60 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	11.1% 1/9 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Cardiac disorders Sinus tachycardia	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, spec	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Vascular disorders Superior vena cava syndrome	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Vascular disorders Thromboembolic event	5.0% 3/60 • Number of events 3 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	6.2% 3/48 • Number of events 3 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Treatment related secondary malignancy	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Gastrointestinal disorders Typhlitis	3.3% 2/60 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	4.2% 2/48 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Infections and infestations Upper respiratory infection	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/48 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	11.1% 1/9 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Injury, poisoning and procedural complications Vascular access complication	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Investigations White blood cell decreased	5.0% 3/60 • Number of events 6 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	4.2% 2/48 • Number of events 4 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	11.1% 1/9 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Gastrointestinal disorders Abdominal distension	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/48 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Investigations Activated partial thromboplastin time prolonged	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Psychiatric disorders Agitation	3.3% 2/60 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	11.1% 1/9 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Investigations Alanine aminotransferase increased	26.7% 16/60 • Number of events 23 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	22.9% 11/48 • Number of events 17 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	55.6% 5/9 • Number of events 6 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Investigations Alkaline phosphatase increased	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Immune system disorders Allergic reaction	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/48 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	11.1% 1/9 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Immune system disorders Anaphylaxis	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Blood and lymphatic system disorders Anemia	5.0% 3/60 • Number of events 5 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	4.2% 2/48 • Number of events 3 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	11.1% 1/9 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Metabolism and nutrition disorders Anorexia	5.0% 3/60 • Number of events 3 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	4.2% 2/48 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Psychiatric disorders Anxiety	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Investigations Aspartate aminotransferase increased	15.0% 9/60 • Number of events 11 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	12.5% 6/48 • Number of events 8 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	33.3% 3/9 • Number of events 3 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Musculoskeletal and connective tissue disorders Back pain	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Investigations Blood bilirubin increased	3.3% 2/60 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	4.2% 2/48 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Eye disorders Blurred vision	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Infections and infestations Catheter related infection	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Hepatobiliary disorders Cholecystitis	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Renal and urinary disorders Chronic kidney disease	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Gastrointestinal disorders Colitis	3.3% 2/60 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	4.2% 2/48 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Psychiatric disorders Confusion	3.3% 2/60 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	11.1% 1/9 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Investigations Creatinine increased	3.3% 2/60 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	11.1% 1/9 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Metabolism and nutrition disorders Dehydration	6.7% 4/60 • Number of events 4 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	8.3% 4/48 • Number of events 4 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Gastrointestinal disorders Diarrhea	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Nervous system disorders Dizziness	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Nervous system disorders Dysphasia	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Respiratory, thoracic and mediastinal disorders Dyspnea	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/48 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	11.1% 1/9 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
General disorders Edema limbs	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Investigations Electrocardiogram QT corrected interval prolonged	3.3% 2/60 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	4.2% 2/48 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Nervous system disorders Encephalopathy	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.

Other adverse events
Measure	Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy) n=60 participants at risk See Detailed Description Asparaginase: Given IT Cyclophosphamide: Given IV Cytarabine: Given IT or IV Dasatinib: Given PO Daunorubicin Hydrochloride: Given IV Dexamethasone: Given IV or PO Etoposide: Given IV Filgrastim: Given IV or SC Hydrocortisone Sodium Succinate: Given IT Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV or PO Mercaptopurine: Given PO Methotrexate: Given IT, PO, or IV Methylprednisolone: Given IV Pegaspargase: Given IM Prednisone: Given PO or IV Radiation Therapy: Some patients undergo cranial RT Vincristine Sulfate: Given IV	Standard-risk n=48 participants at risk Based on Minimal Residual Disease, less than 1%.	High-risk n=9 participants at risk Based on Minimal Residual Disease, great than or equal to 1%.
Gastrointestinal disorders Abdominal pain	11.7% 7/60 • Number of events 7 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	14.6% 7/48 • Number of events 7 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Metabolism and nutrition disorders Acidosis	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Nervous system disorders Acoustic nerve disorder NOS	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Investigations Activated partial thromboplastin time prolonged	3.3% 2/60 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Endocrine disorders Adrenal insufficiency	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/48 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	11.1% 1/9 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Psychiatric disorders Agitation	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Investigations Alanine aminotransferase increased	51.7% 31/60 • Number of events 119 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	60.4% 29/48 • Number of events 114 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	22.2% 2/9 • Number of events 5 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Investigations Alkaline phosphatase increased	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Immune system disorders Allergic reaction	5.0% 3/60 • Number of events 3 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	4.2% 2/48 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	11.1% 1/9 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Gastrointestinal disorders Anal mucositis	3.3% 2/60 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	4.2% 2/48 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Immune system disorders Anaphylaxis	8.3% 5/60 • Number of events 5 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	6.2% 3/48 • Number of events 3 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	22.2% 2/9 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Blood and lymphatic system disorders Anemia	38.3% 23/60 • Number of events 66 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	39.6% 19/48 • Number of events 61 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	33.3% 3/9 • Number of events 4 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Metabolism and nutrition disorders Anorexia	8.3% 5/60 • Number of events 11 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	10.4% 5/48 • Number of events 11 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Psychiatric disorders Anxiety	3.3% 2/60 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	4.2% 2/48 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Infections and infestations Appendicitis	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Musculoskeletal and connective tissue disorders Arthralgia	5.0% 3/60 • Number of events 3 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	4.2% 2/48 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Investigations Aspartate aminotransferase increased	33.3% 20/60 • Number of events 36 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	39.6% 19/48 • Number of events 35 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	11.1% 1/9 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Musculoskeletal and connective tissue disorders Avascular necrosis	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Musculoskeletal and connective tissue disorders Back pain	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Infections and infestations Bladder infection	3.3% 2/60 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	4.2% 2/48 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Investigations Blood bilirubin increased	8.3% 5/60 • Number of events 7 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	6.2% 3/48 • Number of events 5 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	22.2% 2/9 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Infections and infestations Bone infection	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Injury, poisoning and procedural complications Bruising	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/48 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	11.1% 1/9 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Skin and subcutaneous tissue disorders Bullous dermatitis	1.7% 1/60 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Cardiac disorders Cardiac disorders - Other, specify	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/48 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	11.1% 1/9 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Infections and infestations Catheter related infection	5.0% 3/60 • Number of events 8 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	4.2% 2/48 • Number of events 7 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
General disorders Chills	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Nervous system disorders Cognitive disturbance	3.3% 2/60 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	4.2% 2/48 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Gastrointestinal disorders Colitis	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Psychiatric disorders Confusion	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Gastrointestinal disorders Constipation	5.0% 3/60 • Number of events 3 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	4.2% 2/48 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	11.1% 1/9 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Investigations Creatinine increased	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/48 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	11.1% 1/9 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Immune system disorders Cytokine release syndrome	1.7% 1/60 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Metabolism and nutrition disorders Dehydration	6.7% 4/60 • Number of events 5 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	8.3% 4/48 • Number of events 5 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Psychiatric disorders Depression	5.0% 3/60 • Number of events 3 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Gastrointestinal disorders Diarrhea	15.0% 9/60 • Number of events 13 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	16.7% 8/48 • Number of events 12 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Nervous system disorders Dizziness	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/48 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Infections and infestations Duodenal infection	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	2.1% 1/48 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Gastrointestinal disorders Dysphagia	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/48 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
Respiratory, thoracic and mediastinal disorders Dyspnea	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	0.00% 0/48 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.	11.1% 1/9 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.