An Open-Label Study of JZP-458 (RC-P) in Patients With Acute Lymphoblastic Leukemia (ALL)/Lymphoblastic Lymphoma (LBL)
- Conditions
- Acute Lymphoblastic LeukemiaLymphoblastic Leukemia
- Interventions
- Drug: IM JZP-458Drug: IV JZP-458
- Registration Number
- NCT04145531
- Lead Sponsor
- Jazz Pharmaceuticals
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 229
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description JZP-458 IM 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. JZP-458 IV 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.
- Primary Outcome Measures
Name Time Method Response Rate During the First Course of JZP-458 Administration Baseline up to 2 weeks 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.
Number of Participants With Any Treatment-emergent Adverse Events (TEAEs) Date of written informed consent up to 30 days after last dose of last course, up to approximately 2 years 7 months 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.
- Secondary Outcome Measures
Name Time Method Number of Participants With Last 48-hour NSAA Level ≥ 0.1 IU/mL During The First Course (6 Doses) of JZP-458 Administration Baseline up to 2 weeks Blood samples were collected for serum asparaginase activity level determination.
Number of Participants With Last NSAA Levels ≥ 0.4 IU/mL During The First Course (6 Doses) of JZP-458 Administration Baseline up to 2 weeks Blood samples were collected for serum asparaginase activity level determination.
Mean Serum Asparaginase Activity Levels in First Course of JZP-458 Administration Up to 2 weeks (6 doses) Serum asparaginase levels serve as a surrogate marker for asparagine depletion. Mean serum asparaginase activity levels in Course 1 are reported.
Number of Participants Who Are Anti-drug Antibody Positive or Negative Against JZP-458 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 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.
Trial Locations
- Locations (74)
Scottish Rite Hospital
🇺🇸Atlanta, Georgia, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Kaiser Permanente - Fontana Medical Center
🇺🇸Fontana, California, United States
Children's Hospital of Orange County Main Campus - Orange
🇺🇸Orange, California, United States
Nemours Children's Specialty Care Jacksonville
🇺🇸Jacksonville, Florida, United States
Kaiser Permanente - Roseville Medical Center
🇺🇸Roseville, California, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Benioff Children's Hospital Oakland
🇺🇸Oakland, California, United States
Johns Hopkins All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Medical City Dallas Hospital
🇺🇸Dallas, Texas, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Kaiser Permanente - Oakland Medical Center
🇺🇸Oakland, California, United States
Nemours Alfred I. Dupont Hospital for Children
🇺🇸Wilmington, Delaware, United States
NYU - Stephen D. Hassenfeld Children's Center for Cancer and Blood Disorders
🇺🇸New York, 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
Washington University School of Medicine in Saint Louis
🇺🇸Saint Louis, Missouri, United States
Ann and Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
🇺🇸Boston, Massachusetts, United States
Kaiser Permanente - San Diego Medical Center
🇺🇸San Diego, California, United States
Children's Minnesota
🇺🇸Minneapolis, Minnesota, United States
Masonic Cancer Center
🇺🇸Minneapolis, Minnesota, United States
Alliance for Childhood Diseases
🇺🇸Las Vegas, Nevada, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
Children's of Alabama
🇺🇸Birmingham, Alabama, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
University of California San Francisco Benioff Children's Hospital - Mission Bay
🇺🇸San Francisco, California, United States
The Children's Hospital at Oklahoma University Medical Center
🇺🇸Oklahoma City, Oklahoma, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Primary Children's Hospital
🇺🇸Salt Lake City, Utah, United States
Victoria Hospital & Children's Hospital
🇨🇦London, Ontario, Canada
Children's Hospital of Eastern Ontario
🇨🇦Ottawa, Ontario, Canada
SickKids - The Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Kaiser Permanente - Orange County - Anaheim Medical Center
🇺🇸Anaheim, California, United States
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
Kaiser Permanente- Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
MemorialCare Miller Children's and Women's Hospital Long Beach
🇺🇸Long Beach, California, United States
Connecticut Children's Medical Center
🇺🇸Hartford, Connecticut, United States
Children's National Health System
🇺🇸Washington, District of Columbia, United States
Memorial Medical Office Centre
🇺🇸Hollywood, Florida, United States
Kapi'olani Medical Center for Women and Children
🇺🇸Honolulu, Hawaii, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
East Tennessee Children's Hospital
🇺🇸Knoxville, Tennessee, United States
Methodist Hospital - San Antonio
🇺🇸San Antonio, Texas, United States
Inova Medical Group - Fairfax Hospital
🇺🇸Falls Church, Virginia, United States
Children's Hospital of The King's Daughters
🇺🇸Norfolk, Virginia, United States
Centre Hospitalier Universitaire Sainte-Justine
🇨🇦Montréal, Quebec, Canada
Kaiser Permanente - Downey Medical Center
🇺🇸Downey, California, United States
Providence Sacred Heart Medical Center
🇺🇸Spokane, Washington, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
Kaiser Permanente - Santa Clara Medical Center
🇺🇸Santa Clara, California, United States
Cohen Children's Medical Center
🇺🇸New Hyde Park, New York, United States
Golisano Children's Hospital of Southwest Florida
🇺🇸Fort Myers, Florida, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Massey Cancer Center
🇺🇸Richmond, Virginia, United States
McMaster Children's Hospital
🇨🇦Hamilton, Ontario, Canada
The Montreal Children's Hospital
🇨🇦Montréal, Quebec, Canada
University of Pittsburgh Medical Center - Children's Hospital of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Neurology Clinic, P.C
🇺🇸Cordova, Tennessee, United States
Children's Blood and Cancer Center
🇺🇸Austin, Texas, United States
CancerCare Manitoba - McDermot and Urgent Care Site
🇨🇦Winnipeg, Manitoba, Canada
University of California Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
Smilow Cancer Hospital - New Haven
🇺🇸New Haven, Connecticut, United States
AdventHealth Orlando
🇺🇸Orlando, Florida, United States
Norton Children's Hospital
🇺🇸Louisville, Kentucky, United States
C.S. Mott Children's Hospital
🇺🇸Ann Arbor, Michigan, United States
Wake Forest Baptist Health
🇺🇸Winston-Salem, North Carolina, United States
Morristown Medical Center
🇺🇸Morristown, New Jersey, United States