TriangleNCT04145531 · CITED IN SOURCE DOCUMENTS
An Open-Label Study of JZP-458 (RC-P) in Patients With Acute Lymphoblastic Leukemia (ALL)/Lymphoblastic Lymphoma (LBL)
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE2, PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2023-11-18
This is an open-label, multicenter, dose confirmation, and PK study of JZP-458 in patients (of any age) with ALL/LBL who are hypersensitive to E. coli-derived asparaginases (allergic reaction or silent inactivation). This study is designed to assess the tolerability and efficacy of JZP-458 (only in patients who develop hypersensitivity to an E. coli-derived asparaginase), as measured by asparaginase activity.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Response Rate During the First Course of JZP-458 Administration
Number of Participants With Any Treatment-emergent Adverse Events (TEAEs)
Number of Participants With Last 48-hour NSAA Level ≥ 0.1 IU/mL During The First Course (6 Doses) of JZP-458 Administration
Number of Participants With Last NSAA Levels ≥ 0.4 IU/mL During The First Course (6 Doses) of JZP-458 Administration
Mean Serum Asparaginase Activity Levels in First Course of JZP-458 Administration
Number of Participants Who Are Anti-drug Antibody Positive or Negative Against JZP-458
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Inclusion Criteria: 1. Pediatric and adult patients with a diagnosis of ALL or LBL. 2. Have had an allergic reaction to a long-acting E. coli-derived asparaginase OR have silent inactivation. 3. Have 1 or more courses of E. coli-derived asparaginase remaining in his/her treatment plan. 4. Patients must have, in the opinion of the Investigator, fully recovered from their prior allergic reaction to E. coli-derived asparaginase. Exclusion Criteria: 1. Have previously received asparaginase Erwinia chrysanthemi or JZP-458. 2. Have relapsed ALL or LBL. 3. Are concurrently receiving another investigational agent and/or treated with an investigational device at the same time as JZP-458 (within 48 hours) during Course 1 of JZP-458. 4. Have a history of ≥ Grade 3 pancreatitis. 5. Prior history of asparaginase-associated ≥ Grade 3 hemorrhagic event or asparaginase-associated thrombus requiring anticoagulation therapy, excluding catheter-related thrombotic events.
- healthy Volunteers
- false
- sex
- ALL
- std Ages
- CHILD
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Part A (IM JZP-458) of the study will have 2 IM cohorts: * Cohort 1: a JZP-458 repeat dose/confirmatory cohort; a final IM JZP-458 dose level will be selected, and * Cohort 2: an expansion cohort to confirm the efficacy and safety of the final IM JZP-458 dose level and schedule Part B (IV JZP-458 Dose Confirmation) will be conducted to define the optimal dose of the IV administration of JZP-458 for further study in ALL/LBL patients as a repeated dose. Additional courses of JZP-458 (IM or IV depending on patient's allocation at study enrollment) will be administered based on each patient's original treatment plan for as long as the patient derives clinical benefit.
- intervention Names
- Drug: IM JZP-458
- Drug: IV JZP-458
- label
- JZP-458
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- JZP-458
- description
- IM JZP-458 will be administered in Part A, Cohorts 1 \& 2
- name
- IM JZP-458
- type
- DRUG
- arm Group Labels
- JZP-458
- description
- IV JZP-458 will be administered in Part B
- name
- IV JZP-458
- type
- DRUG
Study design
- allocation
- NA
- intervention Model
- SEQUENTIAL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 229
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- The response rate was defined as the number (proportion) of patients with the last 72-hour nadir serum asparaginase activity (NSAA) level ≥ 0.1 IU/mL during the first course of IM JZP-458. Blood samples were collected for serum asparaginase activity level determination.
- measure
- Response Rate During the First Course of JZP-458 Administration
- time Frame
- Baseline up to 2 weeks
- description
- An adverse event (AE) is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered related to study drug. AEs were classified by the Investigator using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
- measure
- Number of Participants With Any Treatment-emergent Adverse Events (TEAEs)
- time Frame
- Date of written informed consent up to 30 days after last dose of last course, up to approximately 2 years 7 months
- secondary Outcomes
- description
- Blood samples were collected for serum asparaginase activity level determination.
- measure
- Number of Participants With Last 48-hour NSAA Level ≥ 0.1 IU/mL During The First Course (6 Doses) of JZP-458 Administration
- time Frame
- Baseline up to 2 weeks
- description
- Blood samples were collected for serum asparaginase activity level determination.
- measure
- Number of Participants With Last NSAA Levels ≥ 0.4 IU/mL During The First Course (6 Doses) of JZP-458 Administration
- time Frame
- Baseline up to 2 weeks
- description
- Serum asparaginase levels serve as a surrogate marker for asparagine depletion. Mean serum asparaginase activity levels in Course 1 are reported.
- measure
- Mean Serum Asparaginase Activity Levels in First Course of JZP-458 Administration
- time Frame
- Up to 2 weeks (6 doses)
- description
- Blood samples were collected for immunogenicity analysis. Anti-drug antibody positive (ADA+) participants were those with a positive result on the first test and also a positive result on the confirmatory test. Anti-drug antibody negative (ADA-) participants had a negative result on the first test.
- measure
- Number of Participants Who Are Anti-drug Antibody Positive or Negative Against JZP-458
- time Frame
- Baseline up to 30 days (ADA- samples) after last dose of last course and up to 6 months (ADA+ samples) after last dose of last course, up to approximately 2 years 7 months
Full study description
- brief Summary
- This is an open-label, multicenter, dose confirmation, and PK study of JZP-458 in patients (of any age) with ALL/LBL who are hypersensitive to E. coli-derived asparaginases (allergic reaction or silent inactivation). This study is designed to assess the tolerability and efficacy of JZP-458 (only in patients who develop hypersensitivity to an E. coli-derived asparaginase), as measured by asparaginase activity.
Source references
- references
- citation
- Maese L, Loh ML, Choi MR, Lin T, Aoki E, Zanette M, Agarwal S, Iannone R, Silverman JA, Silverman LB, Raetz EA, Rau RE. Recombinant Erwinia asparaginase (JZP458) in acute lymphoblastic leukemia: results from the phase 2/3 AALL1931 study. Blood. 2023 Feb 16;141(7):704-712. doi: 10.1182/blood.2022016923.
- pmid
- 36108304
- type
- RESULT
- citation
- Maese L, Loh ML, Choi MR, Agarwal S, Aoki E, Liang Y, Lin T, Girgis S, Chen C, Roller S, Chandrasekaran V, Iannone R, Silverman LB, Raetz EA, Rau RE. Recombinant Erwinia asparaginase (JZP458) in ALL/LBL: complete follow-up of the Children's Oncology Group AALL1931 study. Blood Adv. 2025 Jan 14;9(1):66-77. doi: 10.1182/bloodadvances.2024013346.
- pmid
- 39454281
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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- ho have developed hypersensitivity to E. coli -derived asparaginase as a component of a multi-agent chemotherapeutic regimen was evaluated in Study JZP458-201 (NCT04145531), an open-label, multi-cohort, multi-center trial. In this trial, RYLAZE was administered at various dosages and routes of administration every Monday, Wednesd
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Preserved source evidence · Not medical advice