Adult Acute Lymphoblastic Leukemia, Childhood Acute Lymphoblastic Leukemia
Conditions
Brief summary
This clinical trial is studying the side effects of Erwinia asparaginase and what happens to the drug in the body in treating young patients with acute lymphoblastic leukemia who are allergic to PEG-asparaginase. Drugs used in chemotherapy, such as Erwinia asparaginase, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.
Detailed description
PRIMARY OBJECTIVES: I. To determine if the 48-hour trough serum asparaginase activity is ? 0.1 IU/mL in young patients with acute lymphoblastic leukemia treated with Erwinia asparaginase after allergy to PEG-asparaginase. II. To determine the frequency of asparaginase-related toxicity in these patients. III. To characterize the pharmacokinetics of Erwinia asparaginase in these patients. SECONDARY OBJECTIVES: I. To compare serum asparaginase activity and serum asparagine concentration between patients treated with Erwinia asparaginase on this trial and historical controls treated with PEG-asparaginase on CCG-1961 and CCG-1962. II. To determine the 72-hour serum asparaginase activity on days 8 or 11 or 13 based on the starting date of Erwinia asparaginase therapy. III. To determine the presence of anti-Erwinia asparaginase antibodies in patients treated with a course(s) of Erwinia asparaginase following clinical allergy to PEG-asparaginase (PEG, pegaspargase). IV. To determine if serum asparagine is adequately depleted on days 12 or 13 in a subset of these patients. OUTLINE: This is a multicenter study. Patients receive 6 doses of Erwinia asparaginase 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. Blood samples are collected periodically for pharmacokinetic, pharmacodynamic, and antibody studies. After completion of study treatment, patients are followed periodically.
Interventions
DRUGAsparaginase
Given IM
OTHERLaboratory Biomarker Analysis
Correlative studies
OTHERPharmacological Study
Correlative studies
Sponsors
National Cancer Institute (NCI)
Children's Oncology Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 30 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of acute lymphoblastic leukemia * Concurrently enrolled on a frontline Children's Oncology Group treatment trial (i.e., COG-AALL0232 or COG-AALL0531, COG-AALL0331, or COG-AALL0434) at a participating institution * Must have 1 or more courses of asparaginase remaining to be administered on the treatment protocol * Must have had a grade ? 2 hypersensitivity reaction to PEG-asparaginase * No history of pancreatitis ? grade 2 * No prior Erwinia asparaginase
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Trough Serum Asparaginase Activity ≥ 0.1 IU/mL | 48 hours post administration of Erwinia asparaginase | Percentage of participants who had trough serum asparaginase activity ≥ 0.1 IU/mL in the blood 48 hours post administration of Erwinia asparaginase |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determine if Plasma Asparagine is Adequately Depleted | On days 12 or 13 | Plasma asparagine depletion will be determined in a subset of 20 patients limited to participating Phase I Institutions. |
| Presence of Anti-Erwinia Asparaginase Antibodies in Children Treated With a Course(s) of Erwinase® Following Clinical Allergy to PEG-asparaginase | At baseline, prior to doses 4, 5, and 6 and on days 15 and 22 | 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. |
| Percentage of Participants Who Experienced Toxicities | up to 1 year | The percentage of participants who experienced toxicities: Allergy rate, Hyperglycemia Rate, Pancreatitis Rate, Hemorrhage/Thrombosis Rate |
Countries
United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 59 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Disease progression/ relapse during Tx | 1 |
| Overall Study | ≥ Grade 2 allergy | 7 |
| Overall Study | Ineligible | 2 |
| Overall Study | Inevaluable | 2 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Erwinia Asparaginase |
|---|---|
| Age, Categorical <=18 years | 59 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 46 Participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 55 |
| serious Total, serious adverse events | 9 / 55 |
Outcome results
Primary
Percentage of Participants With Trough Serum Asparaginase Activity ≥ 0.1 IU/mL
Percentage of participants who had trough serum asparaginase activity ≥ 0.1 IU/mL in the blood 48 hours post administration of Erwinia asparaginase
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erwinia Asparaginase | Percentage of Participants With Trough Serum Asparaginase Activity ≥ 0.1 IU/mL | 94.5 Percent of participants |
Secondary
Determine if Plasma Asparagine is Adequately Depleted
Plasma asparagine depletion will be determined in a subset of 20 patients limited to participating Phase I Institutions.
Time frame: On days 12 or 13
Population: No data available for this analysis.
Secondary
Percentage of Participants Who Experienced Toxicities
The percentage of participants who experienced toxicities: Allergy rate, Hyperglycemia Rate, Pancreatitis Rate, Hemorrhage/Thrombosis Rate
Time frame: up to 1 year
Population: Patients who had toxicity data collected.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erwinia Asparaginase | Percentage of Participants Who Experienced Toxicities | Allergy Rate | 10.9 percentage of participants |
| Erwinia Asparaginase | Percentage of Participants Who Experienced Toxicities | Hyperglycemia Rate | 10.9 percentage of participants |
| Erwinia Asparaginase | Percentage of Participants Who Experienced Toxicities | Pancreatitis Rate | 1.8 percentage of participants |
| Erwinia Asparaginase | Percentage of Participants Who Experienced Toxicities | Hemorrhage/Thrombosis Rate | 0 percentage of participants |
Secondary
Presence of Anti-Erwinia Asparaginase Antibodies in Children Treated With a Course(s) of Erwinase® Following Clinical Allergy to PEG-asparaginase
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.
Time frame: At baseline, prior to doses 4, 5, and 6 and on days 15 and 22
Population: no data available for this analysis.