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

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04145531
• Other study ID #: JZP458-201
• Secondary ID: AALL1931
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: December 27, 2019
• Est. completion date: July 13, 2022

Study information

• Verified date: November 2023
• Source: Jazz Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 229
• Est. completion date: July 13, 2022
• Est. primary completion date: July 13, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Lymphoblastic Leukemia
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

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

Locations

Country	Name	City	State
Canada	McMaster Children's Hospital	Hamilton	Ontario
Canada	Victoria Hospital & Children's Hospital	London	Ontario
Canada	Centre Hospitalier Universitaire Sainte-Justine	Montréal	Quebec
Canada	The Montreal Children's Hospital	Montréal	Quebec
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	SickKids - The Hospital for Sick Children	Toronto	Ontario
Canada	CancerCare Manitoba - McDermot and Urgent Care Site	Winnipeg	Manitoba
United States	Kaiser Permanente - Orange County - Anaheim Medical Center	Anaheim	California
United States	C.S. Mott Children's Hospital	Ann Arbor	Michigan
United States	Scottish Rite Hospital	Atlanta	Georgia
United States	Children's Blood and Cancer Center	Austin	Texas
United States	Children's of Alabama	Birmingham	Alabama
United States	Dana-Farber/Boston Children's Cancer and Blood Disorders Center	Boston	Massachusetts
United States	Ann and Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Neurology Clinic, P.C	Cordova	Tennessee
United States	Medical City Dallas Hospital	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Kaiser Permanente - Downey Medical Center	Downey	California
United States	Inova Medical Group - Fairfax Hospital	Falls Church	Virginia
United States	Kaiser Permanente - Fontana Medical Center	Fontana	California
United States	Golisano Children's Hospital of Southwest Florida	Fort Myers	Florida
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Memorial Medical Office Centre	Hollywood	Florida
United States	Kapi'olani Medical Center for Women and Children	Honolulu	Hawaii
United States	Texas Children's Hospital	Houston	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Nemours Children's Specialty Care Jacksonville	Jacksonville	Florida
United States	East Tennessee Children's Hospital	Knoxville	Tennessee
United States	Alliance for Childhood Diseases	Las Vegas	Nevada
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	Loma Linda University Medical Center	Loma Linda	California
United States	MemorialCare Miller Children's and Women's Hospital Long Beach	Long Beach	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Kaiser Permanente- Los Angeles Medical Center	Los Angeles	California
United States	Norton Children's Hospital	Louisville	Kentucky
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Children's Minnesota	Minneapolis	Minnesota
United States	Masonic Cancer Center	Minneapolis	Minnesota
United States	Morristown Medical Center	Morristown	New Jersey
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Smilow Cancer Hospital - New Haven	New Haven	Connecticut
United States	Cohen Children's Medical Center	New Hyde Park	New York
United States	Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Memorial Sloan-Kettering Cancer Center - New York	New York	New York
United States	NYU - Stephen D. Hassenfeld Children's Center for Cancer and Blood Disorders	New York	New York
United States	Children's Hospital of The King's Daughters	Norfolk	Virginia
United States	Benioff Children's Hospital Oakland	Oakland	California
United States	Kaiser Permanente - Oakland Medical Center	Oakland	California
United States	The Children's Hospital at Oklahoma University Medical Center	Oklahoma City	Oklahoma
United States	Children's Hospital of Orange County Main Campus - Orange	Orange	California
United States	AdventHealth Orlando	Orlando	Florida
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	University of Pittsburgh Medical Center - Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Massey Cancer Center	Richmond	Virginia
United States	Kaiser Permanente - Roseville Medical Center	Roseville	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Washington University School of Medicine in Saint Louis	Saint Louis	Missouri
United States	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida
United States	Primary Children's Hospital	Salt Lake City	Utah
United States	Methodist Hospital - San Antonio	San Antonio	Texas
United States	Kaiser Permanente - San Diego Medical Center	San Diego	California
United States	University of California San Francisco Benioff Children's Hospital - Mission Bay	San Francisco	California
United States	Kaiser Permanente - Santa Clara Medical Center	Santa Clara	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	Providence Sacred Heart Medical Center	Spokane	Washington
United States	Children's National Health System	Washington	District of Columbia
United States	Nemours Alfred I. Dupont Hospital for Children	Wilmington	Delaware
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Jazz Pharmaceuticals	Children's Oncology Group (COG)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

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 1 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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)
Secondary	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