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

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Lymphoblastic Leukemia; Lymphoblastic Leukemia
• Intervention / Treatment: Drug: IM JZP-458; Drug: IV JZP-458

• Study Type: Interventional
• Enrollment (Actual): 229
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba - McDermot and Urgent Care Site
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster Children's Hospital
    • London, Ontario, Canada, N6C 2V5
      • Victoria Hospital & Children's Hospital
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • SickKids - The Hospital for Sick Children
  • Quebec
    • Montréal, Quebec, Canada, H3T 1C5
      • Centre Hospitalier Universitaire Sainte-Justine
    • Montréal, Quebec, Canada, H4A 3J1
      • The Montreal Children's Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Children's of Alabama
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital
  • California
    • Anaheim, California, United States, 92806
      • Kaiser Permanente - Orange County - Anaheim Medical Center
    • Downey, California, United States, 90242
      • Kaiser Permanente - Downey Medical Center
    • Fontana, California, United States, 92335
      • Kaiser Permanente - Fontana Medical Center
    • Loma Linda, California, United States, 92350
      • Loma Linda University Medical Center
    • Long Beach, California, United States, 90806
      • MemorialCare Miller Children's and Women's Hospital Long Beach
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente- Los Angeles Medical Center
    • Oakland, California, United States, 94609
      • Benioff Children's Hospital Oakland
    • Oakland, California, United States, 94611
      • Kaiser Permanente - Oakland Medical Center
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County Main Campus - Orange
    • Roseville, California, United States, 95661
      • Kaiser Permanente - Roseville Medical Center
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
    • San Diego, California, United States, 92120
      • Kaiser Permanente - San Diego Medical Center
    • San Francisco, California, United States, 94158
      • University of California San Francisco Benioff Children's Hospital - Mission Bay
    • Santa Clara, California, United States, 95051
      • Kaiser Permanente - Santa Clara Medical Center
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Connecticut Children's Medical Center
    • New Haven, Connecticut, United States, 06511
      • Smilow Cancer Hospital - New Haven
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Nemours Alfred I. Dupont Hospital for Children
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Health System
  • Florida
    • Fort Myers, Florida, United States, 33908
      • Golisano Children's Hospital of Southwest Florida
    • Hollywood, Florida, United States, 33021
      • Memorial Medical Office Centre
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Specialty Care Jacksonville
    • Orlando, Florida, United States, 32803
      • AdventHealth Orlando
    • Saint Petersburg, Florida, United States, 33701
      • Johns Hopkins All Children's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Scottish Rite Hospital
  • Hawaii
    • Honolulu, Hawaii, United States, 96826
      • Kapi'olani Medical Center for Women and Children
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann and Robert H. Lurie Children's Hospital of Chicago
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Children's Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber/Boston Children's Cancer and Blood Disorders Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • C.S. Mott Children's Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Children's Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Masonic Cancer Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine in Saint Louis
  • Nevada
    • Las Vegas, Nevada, United States, 89135
      • Alliance for Childhood Diseases
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
  • New York
    • New Hyde Park, New York, United States, 11040
      • Cohen Children's Medical Center
    • New York, New York, United States, 10032
      • Herbert Irving Comprehensive Cancer Center
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center - New York
    • New York, New York, United States, 10016
      • NYU - Stephen D. Hassenfeld Children's Center for Cancer and Blood Disorders
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • The Children's Hospital at Oklahoma University Medical Center
  • Oregon
    • Portland, Oregon, United States, 97201
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • University of Pittsburgh Medical Center - Children's Hospital of Pittsburgh
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Neurology Clinic, P.C
    • Knoxville, Tennessee, United States, 37913
      • East Tennessee Children's Hospital
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Austin, Texas, United States, 78723
      • Children's Blood and Cancer Center
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75230
      • Medical City Dallas Hospital
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
    • San Antonio, Texas, United States, 78229
      • Methodist Hospital - San Antonio
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Primary Children's Hospital
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Medical Group - Fairfax Hospital
    • Norfolk, Virginia, United States, 23507
      • Children's Hospital of The King's Daughters
    • Richmond, Virginia, United States, 23220
      • Massey Cancer Center
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital
    • Spokane, Washington, United States, 99204
      • Providence Sacred Heart Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: JZP-458; 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; IM JZP-458 will be administered in Part A, Cohorts 1 & 2; Drug: IV JZP-458; IV JZP-458 will be administered in Part B

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals
• Collaborators: Children's Oncology Group (COG)

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 27, 2019
• Primary Completion (Actual): July 13, 2022
• Study Completion (Actual): July 13, 2022

Study Registration Dates

• First Submitted: October 28, 2019
• First Submitted That Met QC Criteria: October 29, 2019
• First Posted (Actual): October 30, 2019

Study Record Updates

• Last Update Posted (Estimated): November 17, 2023
• Last Update Submitted That Met QC Criteria: November 15, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: ALL; Leukemia; Asparaginase; LBL; Childhood acute lymphoblastic leukemia
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
• Other Study ID Numbers: JZP458-201; AALL1931 (Other Identifier: Children's Oncology Group)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No