An Open-Label Study of JZP-458 (RC-P) in Patients With Acute Lymphoblastic Leukemia (ALL)/Lymphoblastic Lymphoma (LBL)

Study Overview
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Brief Summary
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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.

Official Title
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An Open-Label, Multicenter Study of Recombinant Crisantaspase Produced in Pseudomonas Fluorescens (RC-P) in Patients With Acute Lymphoblastic Leukemia (ALL)/Lymphoblastic Lymphoma (LBL) Following Hypersensitivity to E. Coli-derived Asparaginases

Conditions
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Acute Lymphoblastic Leukemia, Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: IM JZP-458
* Drug: IV JZP-458


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pediatric and adult patients with a diagnosis of ALL or LBL. Have had an allergic reaction to a long-acting E. coli-derived asparaginase OR have silent inactivation. Have 1 or more courses of E. coli-derived asparaginase remaining in his/her treatment plan. Patients must have, in the opinion of the Investigator, fully recovered from their prior allergic reaction to E. coli-derived asparaginase. Exclusion Criteria: Have previously received asparaginase Erwinia chrysanthemi or JZP-458. Have relapsed ALL or LBL. 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. Have a history of ≥ Grade 3 pancreatitis. Prior history of asparaginase-associated ≥ Grade 3 hemorrhagic event or asparaginase-associated thrombus requiring anticoagulation therapy, excluding catheter-related thrombotic events.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JZP-458<br>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. | Drug: IM JZP-458<br>* IM JZP-458 will be administered in Part A, Cohorts 1 & 2<br>Drug: IV JZP-458<br>* IV JZP-458 will be administered in Part B<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate During the First Course of JZP-458 Administration | 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. | Baseline up to 2 weeks | 
| Number of Participants With Any Treatment-emergent Adverse Events (TEAEs) | 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. | Date of written informed consent up to 30 days after last dose of last course, up to approximately 2 years 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Last 48-hour NSAA Level ≥ 0.1 IU/mL During The First Course (6 Doses) of JZP-458 Administration | Blood samples were collected for serum asparaginase activity level determination. | Baseline up to 2 weeks | 
| Number of Participants With Last NSAA Levels ≥ 0.4 IU/mL During The First Course (6 Doses) of JZP-458 Administration | Blood samples were collected for serum asparaginase activity level determination. | Baseline up to 2 weeks | 
| Mean Serum Asparaginase Activity Levels in First Course of JZP-458 Administration | Serum asparaginase levels serve as a surrogate marker for asparagine depletion. Mean serum asparaginase activity levels in Course 1 are reported. | Up to 2 weeks (6 doses) | 
| Number of Participants Who Are Anti-drug Antibody Positive or Negative Against JZP-458 | 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. | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALL, LBL, Asparaginase, Leukemia, Childhood acute lymphoblastic leukemia