Trial Outcomes & Findings for Erwinia Asparaginase After Allergy to PEG-Asparaginase in Treating Young Patients With Acute Lymphoblastic Leukemia (NCT NCT00537030)

Last Updated: 2019-07-09

Results Overview

Percentage of participants who had trough serum asparaginase activity ≥ 0.1 IU/mL in the blood 48 hours post administration of Erwinia asparaginase

Recruitment status

COMPLETED

Study phase

Target enrollment

59 participants

Primary outcome timeframe

48 hours post administration of Erwinia asparaginase

Results posted on

2019-07-09

Participant Flow

Confirmation of the patient ineligibility was not confirmed by the COG study team until the patient received their first dose of Erwinia. Patient was removed from the COG frontline study (AALL08P1) prior to enrollment of this study.

Participant milestones

Participant milestones
Measure	Erwinia Asparaginase Patients receive 6 doses of Erwinia asparaginase (dosage 25,000 IU/m2 intramuscularly (IM) on a Monday/Wednesday/Friday schedule as a replacement for each scheduled dose of PEG-asparaginase remaining on the original treatment protocol. All other chemotherapy continues according to the original treatment protocol. pharmacological study : Correlative studies laboratory biomarker analysis : Correlative studies asparaginase : Given IM
Overall Study STARTED	59
Overall Study COMPLETED	43
Overall Study NOT COMPLETED	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Erwinia Asparaginase Patients receive 6 doses of Erwinia asparaginase (dosage 25,000 IU/m2 intramuscularly (IM) on a Monday/Wednesday/Friday schedule as a replacement for each scheduled dose of PEG-asparaginase remaining on the original treatment protocol. All other chemotherapy continues according to the original treatment protocol. pharmacological study : Correlative studies laboratory biomarker analysis : Correlative studies asparaginase : Given IM
Overall Study Physician Decision	2
Overall Study Withdrawal by Subject	2
Overall Study ≥ Grade 2 allergy	7
Overall Study Disease progression/ relapse during Tx	1
Overall Study Ineligible	2
Overall Study Inevaluable	2

Baseline Characteristics

Erwinia Asparaginase After Allergy to PEG-Asparaginase in Treating Young Patients With Acute Lymphoblastic Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Erwinia Asparaginase n=59 Participants Patients receive 6 doses of Erwinia asparaginase (dosage 25,000 IU/m2 intramuscularly (IM) on a Monday/Wednesday/Friday schedule as a replacement for each scheduled dose of PEG-asparaginase remaining on the original treatment protocol. All other chemotherapy continues according to the original treatment protocol. pharmacological study : Correlative studies laboratory biomarker analysis : Correlative studies asparaginase : Given IM
Age, Categorical <=18 years	59 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants
Sex: Female, Male Male	35 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	39 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants
Race (NIH/OMB) White	46 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: 48 hours post administration of Erwinia asparaginase

Population: Of the 59 enrolled participants, there were 2 ineligible and 2 in-evaluable participants. From the remaining 55 participants, 52 participants had an acceptable sample that could be reported on.

Percentage of participants who had trough serum asparaginase activity ≥ 0.1 IU/mL in the blood 48 hours post administration of Erwinia asparaginase

Outcome measures

Outcome measures
Measure	Erwinia Asparaginase n=52 Participants Patients receive 6 doses of Erwinia asparaginase (dosage 25,000 IU/m2 intramuscularly (IM) on a Monday/Wednesday/Friday schedule as a replacement for each scheduled dose of PEG-asparaginase remaining on the original treatment protocol. All other chemotherapy continues according to the original treatment protocol. pharmacological study : Correlative studies laboratory biomarker analysis : Correlative studies asparaginase : Given IM
Percentage of Participants With Trough Serum Asparaginase Activity ≥ 0.1 IU/mL	94.5 Percent of participants

SECONDARY outcome

Timeframe: On days 12 or 13

Population: No data available for this analysis.

Plasma asparagine depletion will be determined in a subset of 20 patients limited to participating Phase I Institutions.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At baseline, prior to doses 4, 5, and 6 and on days 15 and 22

Population: no data available for this analysis.

An ELISA (enzyme-linked immunosorbent assay) method will be used to determine the presence of specific anti-Erwinia and anti-PEG-asparaginase antibodies at baseline, and of specific anti-Erwinia asparaginase antibodies after first and subsequent exposures to Erwinase®. The rate of antibody formation will be described and compared informally to experience in CCG-1962 and 1961. Serum asparaginase activity will be compared during Erwinase® courses as an indication of the neutralizing effect of antibodies on the enzyme effect.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 1 year

Population: Patients who had toxicity data collected.

The percentage of participants who experienced toxicities: Allergy rate, Hyperglycemia Rate, Pancreatitis Rate, Hemorrhage/Thrombosis Rate

Outcome measures

Outcome measures
Measure	Erwinia Asparaginase n=55 Participants Patients receive 6 doses of Erwinia asparaginase (dosage 25,000 IU/m2 intramuscularly (IM) on a Monday/Wednesday/Friday schedule as a replacement for each scheduled dose of PEG-asparaginase remaining on the original treatment protocol. All other chemotherapy continues according to the original treatment protocol. pharmacological study : Correlative studies laboratory biomarker analysis : Correlative studies asparaginase : Given IM
Percentage of Participants Who Experienced Toxicities Allergy Rate	10.9 percentage of participants
Percentage of Participants Who Experienced Toxicities Hyperglycemia Rate	10.9 percentage of participants
Percentage of Participants Who Experienced Toxicities Pancreatitis Rate	1.8 percentage of participants
Percentage of Participants Who Experienced Toxicities Hemorrhage/Thrombosis Rate	0 percentage of participants

Adverse Events

Erwinia Asparaginase

Serious events: 9 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Erwinia Asparaginase n=55 participants at risk Patients receive 6 doses of Erwinia asparaginase (dosage 25,000 IU/m2 intramuscularly (IM) on a Monday/Wednesday/Friday schedule as a replacement for each scheduled dose of PEG-asparaginase remaining on the original treatment protocol. All other chemotherapy continues according to the original treatment protocol. pharmacological study : Correlative studies laboratory biomarker analysis : Correlative studies asparaginase : Given IM
Blood and lymphatic system disorders Febrile neutropenia	1.8% 1/55 Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. There were 2 ineligible and 2 in-evaluable patients excluded from reporting of adverse events, leaving a total of 55 participants included in the AE
General disorders Fever	1.8% 1/55 Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. There were 2 ineligible and 2 in-evaluable patients excluded from reporting of adverse events, leaving a total of 55 participants included in the AE
Immune system disorders Allergic reaction	3.6% 2/55 Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. There were 2 ineligible and 2 in-evaluable patients excluded from reporting of adverse events, leaving a total of 55 participants included in the AE
Infections and infestations Infections and infestations - Other, specify	7.3% 4/55 Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. There were 2 ineligible and 2 in-evaluable patients excluded from reporting of adverse events, leaving a total of 55 participants included in the AE
Investigations Alanine aminotransferase increased	1.8% 1/55 Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. There were 2 ineligible and 2 in-evaluable patients excluded from reporting of adverse events, leaving a total of 55 participants included in the AE
Investigations Aspartate aminotransferase increased	5.5% 3/55 Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. There were 2 ineligible and 2 in-evaluable patients excluded from reporting of adverse events, leaving a total of 55 participants included in the AE
Investigations Blood bilirubin increased	1.8% 1/55 Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. There were 2 ineligible and 2 in-evaluable patients excluded from reporting of adverse events, leaving a total of 55 participants included in the AE
Investigations Neutrophil count decreased	1.8% 1/55 Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. There were 2 ineligible and 2 in-evaluable patients excluded from reporting of adverse events, leaving a total of 55 participants included in the AE
Investigations Platelet count decreased	1.8% 1/55 Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. There were 2 ineligible and 2 in-evaluable patients excluded from reporting of adverse events, leaving a total of 55 participants included in the AE
Investigations White blood cell decreased	1.8% 1/55 Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. There were 2 ineligible and 2 in-evaluable patients excluded from reporting of adverse events, leaving a total of 55 participants included in the AE
Metabolism and nutrition disorders Hyperglycemia	1.8% 1/55 Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. There were 2 ineligible and 2 in-evaluable patients excluded from reporting of adverse events, leaving a total of 55 participants included in the AE

Other adverse events

Other adverse events
Measure	Erwinia Asparaginase n=55 participants at risk Patients receive 6 doses of Erwinia asparaginase (dosage 25,000 IU/m2 intramuscularly (IM) on a Monday/Wednesday/Friday schedule as a replacement for each scheduled dose of PEG-asparaginase remaining on the original treatment protocol. All other chemotherapy continues according to the original treatment protocol. pharmacological study : Correlative studies laboratory biomarker analysis : Correlative studies asparaginase : Given IM
Blood and lymphatic system disorders Febrile neutropenia	5.5% 3/55 Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. There were 2 ineligible and 2 in-evaluable patients excluded from reporting of adverse events, leaving a total of 55 participants included in the AE
Gastrointestinal disorders Nausea	1.8% 1/55 Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. There were 2 ineligible and 2 in-evaluable patients excluded from reporting of adverse events, leaving a total of 55 participants included in the AE
Gastrointestinal disorders Pancreatitis	1.8% 1/55 Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. There were 2 ineligible and 2 in-evaluable patients excluded from reporting of adverse events, leaving a total of 55 participants included in the AE
Gastrointestinal disorders Vomiting	3.6% 2/55 Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. There were 2 ineligible and 2 in-evaluable patients excluded from reporting of adverse events, leaving a total of 55 participants included in the AE
General disorders Fatigue	1.8% 1/55 Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. There were 2 ineligible and 2 in-evaluable patients excluded from reporting of adverse events, leaving a total of 55 participants included in the AE
Immune system disorders Allergic reaction	7.3% 4/55 Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. There were 2 ineligible and 2 in-evaluable patients excluded from reporting of adverse events, leaving a total of 55 participants included in the AE
Injury, poisoning and procedural complications Radiation recall reaction (dermatologic)	1.8% 1/55 Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. There were 2 ineligible and 2 in-evaluable patients excluded from reporting of adverse events, leaving a total of 55 participants included in the AE
Investigations Alanine aminotransferase increased	7.3% 4/55 Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. There were 2 ineligible and 2 in-evaluable patients excluded from reporting of adverse events, leaving a total of 55 participants included in the AE
Investigations Aspartate aminotransferase increased	7.3% 4/55 Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. There were 2 ineligible and 2 in-evaluable patients excluded from reporting of adverse events, leaving a total of 55 participants included in the AE
Investigations Blood bilirubin increased	7.3% 4/55 Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. There were 2 ineligible and 2 in-evaluable patients excluded from reporting of adverse events, leaving a total of 55 participants included in the AE
Investigations Lipase increased	1.8% 1/55 Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. There were 2 ineligible and 2 in-evaluable patients excluded from reporting of adverse events, leaving a total of 55 participants included in the AE
Metabolism and nutrition disorders Hyperglycemia	9.1% 5/55 Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. There were 2 ineligible and 2 in-evaluable patients excluded from reporting of adverse events, leaving a total of 55 participants included in the AE
Metabolism and nutrition disorders Hypoalbuminemia	3.6% 2/55 Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. There were 2 ineligible and 2 in-evaluable patients excluded from reporting of adverse events, leaving a total of 55 participants included in the AE
Nervous system disorders Headache	1.8% 1/55 Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. There were 2 ineligible and 2 in-evaluable patients excluded from reporting of adverse events, leaving a total of 55 participants included in the AE
Psychiatric disorders Agitation	1.8% 1/55 Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. There were 2 ineligible and 2 in-evaluable patients excluded from reporting of adverse events, leaving a total of 55 participants included in the AE
Skin and subcutaneous tissue disorders Urticaria	1.8% 1/55 Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. There were 2 ineligible and 2 in-evaluable patients excluded from reporting of adverse events, leaving a total of 55 participants included in the AE

Additional Information

Results Reporting Coordinator

Children's Oncology Group

Phone: 626-447-0064

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place