A Clinical Study of SHP674 (Pegaspargase) in Participants... | NCT04067518

NCT04067518

Status Module

Sponsor/Collaborators Module

Name	Class
Kyowa Kirin Co., Ltd.	INDUSTRY
ADIR, a Servier Group company	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
SHP674	Experimental	Part 1: Participants with ALL who were stratified into the standard risk (SR) or intermediate risk (IR) groups received total 3 doses of SHP674 in the 36-week treatment period and who were stratified into the high risk (HR) group received total 8 doses of SHP674 in the 45-week treatment period. Part 2: Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674 in the 41-week treatment period and who were stratified into the HR group received total 8 doses of SHP674 in the 45-week treatment period.	Biological: SHP674

Interventions

Name	Type	Description	Arm Group Labels	Other Names
SHP674	Biological	SHP674: powder for solution for injection, IV (administered by 1 to 2 hours of drip infusion), dose determination : if BSA ≥0.6 m^2: 2500 IU/m^2 every 14 days if BSA <0.6 m^2: 82.5 IU/kg every 14 days

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Part 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and SHP-674-Related TEAEs During the Tolerability Assessment Period	An adverse event (AE) is defined as any untoward medical occurrence in a participant after signing informed consent. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease, whether or not it is related to the investigational product. TEAE is defined as any untoward medical occurrence in a participant who received an investigational product which occurs during the period from Day 1 of the pre-treatment phase to 30 (+7) days after the last dose of investigational product, or until the start of a new therapy, whichever occurs first. A related adverse event signifies that there is a reasonable causal relationship between study treatment and an AE.	Up to 30 days after last dose of study drug (approximately 49 weeks)
Part 2: Percentage of Participants Who Achieved a Plasma Asparaginase Activity of ≥0.1 International Units Per Milliliter (IU/mL) 14 Days (336 Hours) After the First Dose of SHP674		14 days after the first dose of SHP674

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Anti-Drug (SHP674) Antibody (ADA) (Part 1 and Part 2)		Predose and 25 days post dose (Part 1 and Part 2)
Percentage of Participants With Anti-Polyethylene Glycol (PEG) Antibody (Part 1 and Part 2)		Predose and 25 days post dose (Part 1 and part 2)

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Chitose Ogawa, MD	National Cancer Center Hospital, Tokyo JAPAN	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Kagoshima University Hospital Department of Pediatrics		Kagoshima			Japan
Kobe Children's Hospital Department of Hematology/Oncology

References Module

Label	URL
Find Results on Servier Clinical Trial Data website	View source

ID	Type	URL	Comment
	Individual Participant Data Set	View IPD

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Part 1: SHP674	Participants with ALL who were stratified into the standard risk (SR) or intermediate risk (IR) groups received total 3 doses of SHP674, 2500 international units per square meter (IU/m^2) (if body surface area [BSA] ≥0.6 m^2) or 82.5 international units per kilogram (IU/kg) (if BSA <0.6 m^2) intravenously (IV) on Day 12 of Remission induction therapy (SR: IA2/IR: IA4) in the 5-week tolerability assessment period, Day 2 of re-induction therapy (conducted twice) in the 36-week treatment period.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jan 22, 2021	May 13, 2022

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study.

Arm/Group Information

ID	Title	Description
BG000	Part 1: SHP674	Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m^2 (if BSA ≥0.6 m^2) or 82.5 IU/kg (if BSA <0.6 m^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4) in the 5-week tolerability assessment period, Day 2 of re-induction therapy (conducted twice) in the 36-week treatment period.
BG001	Part 2: SHP674	Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m^2 (if BSA ≥0.6 m^2) or 82.5 IU/kg (if BSA <0.6 m^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4), Day 2 of re-induction therapy (conducted twice) in the 41-week treatment period and who were stratified into the HR group received total 8 doses of SHP674, 2500 IU/m^2 (if BSA ≥0.6 m^2) or 82.5 IU/kg (if BSA <0.6 m^2) IV on Day 12 of Remission induction therapy (IA4), Day 38 of early consolidation therapy, Day 6 of consolidation therapies (HR3, HR2), Day 7 of consolidation therapy (HR1), Day 2 of re-induction therapy (conducted thrice) in the 45-week treatment period.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG0003 BG00123 BG00226

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00010.2± 2.63 BG0016.7± 4.79 BG0027.1± 4.70

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0002 BG00111 BG002

Race (NIH/OMB)

Definition of racial groups according to NIH (National Institutes of Health) and OMB (Office of Management and Budget)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010

Region of Enrollment

Number

participants

Title

Denominators

Categories

Japan

Title	Measurements
	BG0003 BG00123 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Part 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and SHP-674-Related TEAEs During the Tolerability Assessment Period

An adverse event (AE) is defined as any untoward medical occurrence in a participant after signing informed consent. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease, whether or not it is related to the investigational product. TEAE is defined as any untoward medical occurrence in a participant who received an investigational product which occurs during the period from Day 1 of the pre-treatment phase to 30 (+7) days after the last dose of investigational product, or until the start of a new therapy, whichever occurs first. A related adverse event signifies that there is a reasonable causal relationship between study treatment and an AE.

SAF (Safety Analysis Set) included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As pre-specified in the protocol, this outcome measure is analyzed only for Part 1.

Posted

Count of Participants

Participants

Up to 30 days after last dose of study drug (approximately 49 weeks)

ID	Title	Description
OG000	Part 1: SHP674	Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m^2 (if BSA ≥0.6 m^2) or 82.5 IU/kg (if BSA <0.6 m^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4) in the 5-week tolerability assessment period, Day 2 of re-induction therapy (conducted twice) in the 36-week treatment period.

Units	Counts
Participants	OG0003

Title

Denominators

Categories

TEAEs

Title	Measurements
	OG0003

SHP-674-Related TEAEs

Title	Measurements
	OG0003

Primary

Part 2: Percentage of Participants Who Achieved a Plasma Asparaginase Activity of ≥0.1 International Units Per Milliliter (IU/mL) 14 Days (336 Hours) After the First Dose of SHP674

FAS (Full Analysis Set) included all participants who were enrolled and received SHP674 in Part 2 of the study.

Posted

Number

95% Confidence Interval

participants

14 days after the first dose of SHP674

ID	Title	Description
OG000	Part 2: SHP674	Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m^2 (if BSA ≥0.6 m^2) or 82.5 IU/kg (if BSA <0.6 m^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4), Day 2 of re-induction therapy (conducted twice) in the 41-week treatment period and who were stratified into the HR group received total 8 doses of SHP674, 2500 IU/m^2 (if BSA ≥0.6 m^2) or 82.5 IU/kg (if BSA <0.6 m^2) IV on Day 12 of Remission induction therapy (IA4), Day 38 of early consolidation therapy, Day 6 of consolidation therapies (HR3, HR2), Day 7 of consolidation therapy (HR1), Day 2 of re-induction therapy (conducted thrice) in the 45-week treatment period.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With Anti-Drug (SHP674) Antibody (ADA) (Part 1 and Part 2)

Immunogenicity analysis set (IMAS) included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study and had at least one evaluable post-dose sample. If the pre-dose sample was missing it was considered negative.

Posted

Count of Participants

Participants

Predose and 25 days post dose (Part 1 and Part 2)

ID	Title	Description
OG000	Part 1: SHP674	Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m^2 (if BSA ≥0.6 m^2) or 82.5 IU/kg (if BSA <0.6 m^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4) in the 5-week tolerability assessment period, Day 2 of re-induction therapy (conducted twice) in the 36-week treatment period.
OG001	Part 2: SHP674	Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m^2 (if BSA ≥0.6 m^2) or 82.5 IU/kg (if BSA <0.6 m^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4), Day 2 of re-induction therapy (conducted twice) in the 41-week treatment period and who were stratified into the HR group received total 8 doses of SHP674, 2500 IU/m^2 (if BSA ≥0.6 m^2) or 82.5 IU/kg (if BSA <0.6 m^2) IV on Day 12 of Remission induction therapy (IA4), Day 38 of early consolidation therapy, Day 6 of consolidation therapies (HR3, HR2), Day 7 of consolidation therapy (HR1), Day 2 of re-induction therapy (conducted thrice) in the 45-week treatment period.

Secondary

Percentage of Participants With Anti-Polyethylene Glycol (PEG) Antibody (Part 1 and Part 2)

Posted

Count of Participants

Participants

Predose and 25 days post dose (Part 1 and part 2)

ID	Title	Description
OG000	Part 1: SHP674	Participants with ALL who were stratified into the standard risk (SR) or intermediate risk (IR) groups received total 3 doses of SHP674, 2500 international units per square meter (IU/m^2) (if body surface area [BSA] ≥0.6 m^2) or 82.5 international units per kilogram (IU/kg) (if BSA <0.6 m^2) intravenously (IV) on Day 12 of Remission induction therapy (SR: IA2/IR: IA4) in the 5-week tolerability assessment period, Day 2 of re-induction therapy (conducted twice) in the 36-week treatment period.
OG001	Part 2: SHP674	Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m^2 (if BSA ≥0.6 m^2) or 82.5 IU/kg (if BSA <0.6 m^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4), Day 2 of re-induction therapy (conducted twice) in the 41-week treatment period. Participants with ALL who were stratified into the HR group received total 8 doses of SHP674, 2500 IU/m^2 (if BSA ≥0.6 m^2) or 82.5 IU/kg (if BSA <0.6 m^2) IV on Day 12 of Remission induction therapy (IA4), Day 38 of early consolidation therapy, Day 6 of consolidation therapies (HR3, HR2), Day 7 of consolidation therapy (HR1), Day 2 of re-induction therapy (conducted thrice) in the 45-week treatment period.

Secondary

Part 1: Percentage of Participants Who Achieved a Plasma Asparaginase Activity of ≥0.1 IU/mL 14 Days (336 Hours) After the First Dose of SHP674

SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As pre-specified in the protocol, this outcome measure is analyzed only for Part 1.

Posted

Number

95% Confidence Interval

percentage of participants

14 days after the first dose of SHP674

ID	Title	Description
OG000	Part 1: SHP674	Participants with Acute Lymphoblastic Leukemia (ALL) who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m^2 (if BSA ≥0.6 m^2) or 82.5 IU/kg (if BSA <0.6 m^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4) in the 5-week tolerability assessment period, Day 2 of re-induction therapy (conducted twice) in the 36-week treatment period.

Units	Counts
Participants	OG000

Secondary

Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL

FAS included all participants who were enrolled and received SHP674 in Part 2 of the study. Number analyzed indicates the number of participants analyzed at the specified timepoint.

Posted

Number

95% Confidence Interval

percentage of participants

Day 1 (pre-dose, 5 min, 4 hours, 24 hours post dose), Days 2, 4, 11, 14, 18, 25 post dose

ID	Title	Description
OG000	Part 2: SHP674	Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m^2 (if BSA ≥0.6 m^2) or 82.5 IU/kg (if BSA <0.6 m^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4), Day 2 of re-induction therapy (conducted twice) in the 41-week treatment period and who were stratified into the HR group received total 8 doses of SHP674, 2500 IU/m^2 (if BSA ≥0.6 m^2) or 82.5 IU/kg (if BSA <0.6 m^2) IV on Day 12 of Remission induction therapy (IA4), Day 38 of early consolidation therapy, Day 6 of consolidation therapies (HR3, HR2), Day 7 of consolidation therapy (HR1), Day 2 of re-induction therapy (conducted thrice) in the 45-week treatment period.

Units	Counts
Participants	OG000

Secondary

Survival Rate at 1 Year After the Start of Study Treatment

Survival rate is defined as the percentage of subjects who survived at 1 year after the start of study treatment.

The analysis was performed on the safety set analysis, defined as the set of all subjects who had received at least one dose of SHP674 in Part 1 or Part 2 of the study.

Posted

Count of Participants

Participants

1 year after the start of study treatment (from first dose up to 12 months)

ID	Title	Description
OG000	Part 1: SHP674	Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m^2 (if BSA ≥0.6 m^2) or 82.5 IU/kg (if BSA <0.6 m^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4) in the 5-week tolerability assessment period, Day 2 of re-induction therapy (conducted twice) in the 36-week treatment period.
OG001	Part 2: SHP674	Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m^2 (if BSA ≥0.6 m^2) or 82.5 IU/kg (if BSA <0.6 m^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4), Day 2 of re-induction therapy (conducted twice) in the 41-week treatment period and who were stratified into the HR group received total 8 doses of SHP674, 2500 IU/m^2 (if BSA ≥0.6 m^2) or 82.5 IU/kg (if BSA <0.6 m^2) IV on Day 12 of Remission induction therapy (IA4), Day 38 of early consolidation therapy, Day 6 of consolidation therapies (HR3, HR2), Day 7 of consolidation therapy (HR1), Day 2 of re-induction therapy (conducted thrice) in the 45-week treatment period.

Secondary

Event-free Survival Rate at 1 Year After the Start of Study Treatment

Event-free survival rate is defined as percentage of subjects who did not experience any event and survived at 1 year after the start of study treatment.

The analysis was performed on the safety set analysis, defined as the set of all subjects who had received at least one dose of SHP674 in Part 1 or Part 2 of the study.

Posted

Count of Participants

Participants

1 year after the start of study treatment (from first dose up to 12 months)

ID	Title	Description
OG000	Part 1: SHP674	Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m^2 (if BSA ≥0.6 m^2) or 82.5 IU/kg (if BSA <0.6 m^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4) in the 5-week tolerability assessment period, Day 2 of re-induction therapy (conducted twice) in the 36-week treatment period.
OG001	Part 2: SHP674	Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m^2 (if BSA ≥0.6 m^2) or 82.5 IU/kg (if BSA <0.6 m^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4), Day 2 of re-induction therapy (conducted twice) in the 41-week treatment period and who were stratified into the HR group received total 8 doses of SHP674, 2500 IU/m^2 (if BSA ≥0.6 m^2) or 82.5 IU/kg (if BSA <0.6 m^2) IV on Day 12 of Remission induction therapy (IA4), Day 38 of early consolidation therapy, Day 6 of consolidation therapies (HR3, HR2), Day 7 of consolidation therapy (HR1), Day 2 of re-induction therapy (conducted thrice) in the 45-week treatment period.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Part 1: SHP674	Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m^2 (if BSA ≥0.6 m^2) or 82.5 IU/kg (if BSA <0.6 m^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4) in the 5-week tolerability assessment period, Day 2 of re-induction therapy (conducted twice) in the 36-week treatment period.	0	3	1	3	3	3
EG001	Part 2: SHP674	Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m^2 (if BSA ≥0.6 m^2) or 82.5 IU/kg (if BSA <0.6 m^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4), Day 2 of re-induction therapy (conducted twice) in the 41-week treatment period and who were stratified into the HR group received total 8 doses of SHP674, 2500 IU/m^2 (if BSA ≥0.6 m^2) or 82.5 IU/kg (if BSA <0.6 m^2) IV on Day 12 of Remission induction therapy (IA4), Day 38 of early consolidation therapy, Day 6 of consolidation therapies (HR3, HR2), Day 7 of consolidation therapy (HR1), Day 2 of re-induction therapy (conducted thrice) in the 45-week treatment period.	0	23	10	23	23	23

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pancreatitis acute	Gastrointestinal disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected23 at risk
Stomatitis	Gastrointestinal disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected23 at risk
Vomiting	Gastrointestinal disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected23 at risk
Pyrexia	General disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected23 at risk
Haemophagocytic lymphohistiocytosis	Immune system disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected23 at risk
Cellulitis	Infections and infestations	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected23 at risk
Device related infection	Infections and infestations	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected23 at risk
Gastroenteritis	Infections and infestations	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected23 at risk
Sepsis	Infections and infestations	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected23 at risk
Septic shock	Infections and infestations	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected23 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected23 at risk
Anaphylactic transfusion reaction	Injury, poisoning and procedural complications	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected23 at risk
Platelet count decreased	Investigations	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected23 at risk
Posterior reversible encephalopathy syndrome	Nervous system disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected23 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (23.1)	Systematic Assessment	EG0003 affected3 at risk EG00121 affected23 at risk
Coagulopathy	Blood and lymphatic system disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0015 affected23 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA (23.1)	Systematic Assessment	EG0002 affected3 at risk EG00118 affected23 at risk
Hypoglobulinaemia	Blood and lymphatic system disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0014 affected23 at risk
Cushingoid	Endocrine disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0015 affected23 at risk
Blepharitis	Eye disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected23 at risk
Eye pruritus	Eye disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected23 at risk
Glaucoma	Eye disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected23 at risk
Ocular hyperaemia	Eye disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected23 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (23.1)	Systematic Assessment	EG0003 affected3 at risk EG0016 affected23 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected23 at risk
Anal erosion	Gastrointestinal disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected23 at risk
Cheilitis	Gastrointestinal disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0013 affected23 at risk
Constipation	Gastrointestinal disorders	MedDRA (23.1)	Systematic Assessment	EG0002 affected3 at risk EG00117 affected23 at risk
Dental caries	Gastrointestinal disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0013 affected23 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG00110 affected23 at risk
Gastric haemorrage	Gastrointestinal disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected23 at risk
Gastrointestinal disorder	Gastrointestinal disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0011 affected23 at risk
Hypoasthesia oral	Gastrointestinal disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected23 at risk
Lip dry	Gastrointestinal disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0014 affected23 at risk
Nausea	Gastrointestinal disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG00114 affected23 at risk
Proctalgia	Gastrointestinal disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0012 affected23 at risk
Proctitis	Gastrointestinal disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0014 affected23 at risk
Stomatitis	Gastrointestinal disorders	MedDRA (23.1)	Systematic Assessment	EG0002 affected3 at risk EG00113 affected23 at risk
Vomiting	Gastrointestinal disorders	MedDRA (23.1)	Systematic Assessment	EG0002 affected3 at risk EG00118 affected23 at risk
Catheter site erythema	General disorders	MedDRA (23.1)	Systematic Assessment	EG0002 affected3 at risk EG0011 affected23 at risk
Catheter site pain	General disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0013 affected23 at risk
Chilis	General disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected23 at risk
Feeling abnormal	General disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected23 at risk
Hunger	General disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected23 at risk
Malaise	General disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0014 affected23 at risk
Non-cardiac chest pain	General disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected23 at risk
Pyrexia	General disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG00111 affected23 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0019 affected23 at risk
Hepatic steatosis	Hepatobiliary disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0012 affected23 at risk
Anaphylactic reaction	Immune system disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected23 at risk
Hypersensitivity	Immune system disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0011 affected23 at risk
Hypogammaglobulinaemia	Immune system disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0017 affected23 at risk
Seasonal allergy	Immune system disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected23 at risk
Bacteriaemia	Infections and infestations	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0014 affected23 at risk
Conjunctivitis	Infections and infestations	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected23 at risk
Device related infection	Infections and infestations	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0013 affected23 at risk
Nasopharyngitis	Infections and infestations	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG00110 affected23 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected23 at risk
Accidental overdose	Injury, poisoning and procedural complications	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0014 affected23 at risk
Allergic transfusion reaction	Injury, poisoning and procedural complications	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected23 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0015 affected23 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0012 affected23 at risk
Procedural headache	Injury, poisoning and procedural complications	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected23 at risk
Activated partial thromboplastin time prolonged	Investigations	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0015 affected23 at risk
Alanine aminotransferase increased	Investigations	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG00113 affected23 at risk
Amylase increased	Investigations	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0013 affected23 at risk
Antithrombin III decreased	Investigations	MedDRA (23.1)	Systematic Assessment	EG0003 affected3 at risk EG00112 affected23 at risk
Antithrombin III increased	Investigations	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected23 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG00113 affected23 at risk
Blood albumin decreased	Investigations	MedDRA (23.1)	Systematic Assessment	EG0002 affected3 at risk EG0011 affected23 at risk
Blood bilirubin increased	Investigations	MedDRA (23.1)	Systematic Assessment	EG0003 affected3 at risk EG0019 affected23 at risk
Blood cholesterol increased	Investigations	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0013 affected23 at risk
Blood fibrinogen decreased	Investigations	MedDRA (23.1)	Systematic Assessment	EG0003 affected3 at risk EG00116 affected23 at risk
Blood fibrinogen increased	Investigations	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0011 affected23 at risk
Blood lactate dehydrogenase increased	Investigations	MedDRA (23.1)	Systematic Assessment	EG0002 affected3 at risk EG0012 affected23 at risk
Blood urea increased	Investigations	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0012 affected23 at risk
C-reactive protein increased	Investigations	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected23 at risk
Coagulation test abnormal	Investigations	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected23 at risk
Fibrin D dimer increased	Investigations	MedDRA (23.1)	Systematic Assessment	EG0002 affected3 at risk EG0011 affected23 at risk
Fibrin degradation products increased	Investigations	MedDRA (23.1)	Systematic Assessment	EG0003 affected3 at risk EG0010 affected23 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0019 affected23 at risk
Immunoglobulins decreased	Investigations	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0014 affected23 at risk
Liver function test abnormal	Investigations	MedDRA (23.1)	Systematic Assessment	EG0002 affected3 at risk EG0011 affected23 at risk
Liver function test increased	Investigations	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected23 at risk
Lymphocyte count decreased	Investigations	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0016 affected23 at risk
Neutrophil count decreased	Investigations	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0017 affected23 at risk
Plasmin inhibitor decreased	Investigations	MedDRA (23.1)	Systematic Assessment	EG0003 affected3 at risk EG0013 affected23 at risk
Plasminogen decreased	Investigations	MedDRA (23.1)	Systematic Assessment	EG0003 affected3 at risk EG0013 affected23 at risk
Platelet count decreased	Investigations	MedDRA (23.1)	Systematic Assessment	EG0003 affected3 at risk EG00121 affected23 at risk
Protein total decreased	Investigations	MedDRA (23.1)	Systematic Assessment	EG0002 affected3 at risk EG0011 affected23 at risk
Weight decreased	Investigations	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected23 at risk
Weight increased	Investigations	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0014 affected23 at risk
White blood cell count decreased	Investigations	MedDRA (23.1)	Systematic Assessment	EG0003 affected3 at risk EG00121 affected23 at risk
Central obesity	Metabolism and nutrition disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0011 affected23 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0015 affected23 at risk
Dyslipidaemia	Metabolism and nutrition disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected23 at risk
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0011 affected23 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0015 affected23 at risk
Hyperlipidaemia	Metabolism and nutrition disorders	MedDRA (23.1)	Systematic Assessment	EG0003 affected3 at risk EG0012 affected23 at risk
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG00110 affected23 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0014 affected23 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0015 affected23 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0013 affected23 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0017 affected23 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected23 at risk
Hypoproteinaemia	Metabolism and nutrition disorders	MedDRA (23.1)	Systematic Assessment	EG0002 affected3 at risk EG0018 affected23 at risk
Increased appetite	Metabolism and nutrition disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0011 affected23 at risk
Malnutrition	Metabolism and nutrition disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected23 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0011 affected23 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0014 affected23 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected23 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0013 affected23 at risk
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected23 at risk
Cholinergic syndrome	Nervous system disorders	MedDRA (23.1)	Systematic Assessment	EG0002 affected3 at risk EG0010 affected23 at risk
Dizziness	Nervous system disorders	MedDRA (23.1)	Systematic Assessment	EG0002 affected3 at risk EG0010 affected23 at risk
Headache	Nervous system disorders	MedDRA (23.1)	Systematic Assessment	EG0002 affected3 at risk EG00111 affected23 at risk
Leukoencephalopathy	Nervous system disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected23 at risk
Loss of consciousness	Nervous system disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected23 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected23 at risk
Taste disorder	Nervous system disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected23 at risk
Agitation	Psychiatric disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected23 at risk
Depressed mood	Psychiatric disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0011 affected23 at risk
Depressive symptom	Psychiatric disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0013 affected23 at risk
Discouragement	Psychiatric disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0014 affected23 at risk
Insomnia	Psychiatric disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0016 affected23 at risk
Substance-induced psychotic disorder	Psychiatric disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0013 affected23 at risk
Calculus urinary	Renal and urinary disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0011 affected23 at risk
Glycosuria	Renal and urinary disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected23 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0011 affected23 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0013 affected23 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected23 at risk
Productive sough	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected23 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected23 at risk
Upper respiratory tract inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected23 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected23 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (23.1)	Systematic Assessment	EG0003 affected3 at risk EG00117 affected23 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected23 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected23 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (23.1)	Systematic Assessment	EG0003 affected3 at risk EG00110 affected23 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0013 affected23 at risk
Eczema asteatotic	Skin and subcutaneous tissue disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected23 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0014 affected23 at risk
Ingrowing nail	Skin and subcutaneous tissue disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0011 affected23 at risk
Miliaria	Skin and subcutaneous tissue disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected23 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected23 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0012 affected23 at risk
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected23 at risk
Flushing	Vascular disorders	MedDRA (23.1)	Systematic Assessment	EG0001 affected3 at risk EG0013 affected23 at risk
Hypertension	Vascular disorders	MedDRA (23.1)	Systematic Assessment	EG0000 affected3 at risk EG0017 affected23 at risk

ID	Term
D054198	Precursor Cell Lymphoblastic Leukemia-Lymphoma

Ancestor Terms

ID	Term
D007945	Leukemia, Lymphoid
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases

ID	Term
C042705	pegaspargase

Units	Counts
Participants	OG0003 OG00122