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

NCT04145531 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: JZP458-201AALL1931
• Study Type: interventional
• Target: 229
• Locations: 2 countries
• Sites: 74

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.

Conditions

Acute Lymphoblastic Leukemia; Lymphoblastic Leukemia

Keywords

ALL; LBL; Asparaginase; Leukemia; Childhood acute lymphoblastic leukemia

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• 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

• 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

• Mean Serum Asparaginase Activity Levels in First Course of JZP-458 Administration

  Up to 2 weeks (6 doses)

• 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

Study Arms (1)

JZP-458

EXPERIMENTAL

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; Drug: IV JZP-458

Interventions

IM JZP-458 DRUG

IM JZP-458 will be administered in Part A, Cohorts 1 \& 2

JZP-458

IV JZP-458 DRUG

IV JZP-458 will be administered in Part B

JZP-458

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead
• Children's Oncology Group: collaborator

Study Sites (74)

Children's of Alabama

Birmingham, Alabama, 35233, United States

Location

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

Kaiser Permanente - Orange County - Anaheim Medical Center

Anaheim, California, 92806, United States

Location

Kaiser Permanente - Downey Medical Center

Downey, California, 90242, United States

Location

Kaiser Permanente - Fontana Medical Center

Fontana, California, 92335, United States

Location

Loma Linda University Medical Center

Loma Linda, California, 92350, United States

Location

MemorialCare Miller Children's and Women's Hospital Long Beach

Long Beach, California, 90806, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Kaiser Permanente- Los Angeles Medical Center

Los Angeles, California, 90027, United States

Location

Benioff Children's Hospital Oakland

Oakland, California, 94609, United States

Location

Kaiser Permanente - Oakland Medical Center

Oakland, California, 94611, United States

Location

Children's Hospital of Orange County Main Campus - Orange

Orange, California, 92868, United States

Location

Kaiser Permanente - Roseville Medical Center

Roseville, California, 95661, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Kaiser Permanente - San Diego Medical Center

San Diego, California, 92120, United States

Location

University of California San Francisco Benioff Children's Hospital - Mission Bay

San Francisco, California, 94158, United States

Location

Kaiser Permanente - Santa Clara Medical Center

Santa Clara, California, 95051, United States

Location

Connecticut Children's Medical Center

Hartford, Connecticut, 06106, United States

Location

Smilow Cancer Hospital - New Haven

New Haven, Connecticut, 06511, United States

Location

Nemours Alfred I. Dupont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Children's National Health System

Washington D.C., District of Columbia, 20010, United States

Location

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, 33908, United States

Location

Memorial Medical Office Centre

Hollywood, Florida, 33021, United States

Location

Nemours Children's Specialty Care Jacksonville

Jacksonville, Florida, 32207, United States

Location

AdventHealth Orlando

Orlando, Florida, 32803, United States

Location

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Scottish Rite Hospital

Atlanta, Georgia, 30342, United States

Location

Kapi'olani Medical Center for Women and Children

Honolulu, Hawaii, 96826, United States

Location

Ann and Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Norton Children's Hospital

Louisville, Kentucky, 40202, United States

Location

Dana-Farber/Boston Children's Cancer and Blood Disorders Center

Boston, Massachusetts, 02215, United States

Location

C.S. Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

Children's Minnesota

Minneapolis, Minnesota, 55404, United States

Location

Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Washington University School of Medicine in Saint Louis

St Louis, Missouri, 63110, United States

Location

Alliance for Childhood Diseases

Las Vegas, Nevada, 89135, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Morristown Medical Center

Morristown, New Jersey, 07960, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Cohen Children's Medical Center

New Hyde Park, New York, 11040, United States

Location

NYU - Stephen D. Hassenfeld Children's Center for Cancer and Blood Disorders

New York, New York, 10016, United States

Location

Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

Memorial Sloan-Kettering Cancer Center - New York

New York, New York, 10065, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

The Children's Hospital at Oklahoma University Medical Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oregon Health and Science University

Portland, Oregon, 97201, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Medical Center - Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Neurology Clinic, P.C

Cordova, Tennessee, 38018, United States

Location

East Tennessee Children's Hospital

Knoxville, Tennessee, 37913, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Children's Blood and Cancer Center

Austin, Texas, 78723, United States

Location

Medical City Dallas Hospital

Dallas, Texas, 75230, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Methodist Hospital - San Antonio

San Antonio, Texas, 78229, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

Location

Inova Medical Group - Fairfax Hospital

Falls Church, Virginia, 22042, United States

Location

Children's Hospital of The King's Daughters

Norfolk, Virginia, 23507, United States

Location

Massey Cancer Center

Richmond, Virginia, 23220, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Providence Sacred Heart Medical Center

Spokane, Washington, 99204, United States

Location

CancerCare Manitoba - McDermot and Urgent Care Site

Winnipeg, Manitoba, R3E 0V9, Canada

Location

McMaster Children's Hospital

Hamilton, Ontario, L8N 3Z5, Canada

Location

Victoria Hospital & Children's Hospital

London, Ontario, N6C 2V5, Canada

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

SickKids - The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

The Montreal Children's Hospital

Montreal, Quebec, H4A 3J1, Canada

Location

Related Publications (2)

• 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 RESULT

• 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 DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

Participants in this study received JZP-458 as part of a multi-agent chemotherapeutic regimen.

Results Point of Contact

• Title: Clinical Trial Disclosure & Transparency
• Organization: Jazz Pharmaceuticals

ClinicalTrialDisclosure@JazzPharma.com

215-832-3750

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2019
• First Posted: October 30, 2019
• Study Start: December 27, 2019
• Primary Completion: July 13, 2022
• Study Completion: July 13, 2022
• Last Updated: November 18, 2023
• Results First Posted: November 18, 2023

Record last verified: 2023-11

Locations

US (67); CA (7)