A Dose Confirmation and Pharmacokinetic Study of Pegcrisantaspase Administered as Intravenous (IV) Infusion in Children and Young Adults With Acute Lymphoblastic Leukemia (ALL) /Lymphoblastic Lymphoma (LBL). Following Hypersensitivity to Pegaspargase (Oncaspar)

Phase 2

Terminated

Conditions: Acute Lymphoblastic Leukemia
Lymphoblastic Lymphoma

Interventions: Drug: pegcrisantaspase

Registration Number: NCT02257684

Lead Sponsor: Jazz Pharmaceuticals

Brief Summary: The purpose of this study is to evaluate the effectiveness,safety, and dosage of pegcrisantaspase in patients with Acute Lymphoblastic Leukemia (ALL) / Lymphoblastic Lymphoma (LBL).

Detailed Description: The purpose of the study was to assess the response rate in children and young adults with ALL/LBL and hypersensitivity to pegaspargase defined as the proportion of subjects having a serum asparaginase activity (SAA) level of ≥ 0.1 IU/mL 14 days following the first IV pegcrisantaspase dose in Course 1. Also, to assess the safety of IV pegcrisantaspase therapy in children and young adults with ALL/LBL with hypersensitivity to pegaspargase.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 4

Inclusion Criteria

Have a diagnosis of ALL/LBL
Be > 1 to ≤ 21 years of age at study enrollment
Have had a ≥ Grade 2 allergic reaction (Common Terminology Criteria for Adverse Events [CTCAE] v4.03) to pegaspargase
Have ≥ 1 dose(s) of pegaspargase remaining in his/her treatment plan
Have a documented SAA level that is below the limit of quantitation per the analytical method.
Subjects must have, in the opinion of the investigator, fully recovered from prior allergic reaction to pegaspargase. Subjects must have completed antihistamine, epinephrine, and/or corticosteroid treatment for the allergic reaction ≥ 24 hours prior to pegcrisantaspase administration.
Subjects must have a performance status corresponding to:
- Karnofsky ≥ 50 (for subjects > 16 years of age)
- Lansky ≥ 50 (for subjects ≤ 16 years of age)
Adequate Renal Function Defined as:
- Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m2 or
- A serum creatinine based on age/gender as follows:
Age Maximum Serum Creatinine (mg/dL) Male Female 1 to < 2 years 0.6 0.6 2 to < 6 years 0.8 0.8 6 to < 10 years 1 1 10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4

≥ 16 years 1.7 1.4

The threshold creatinine values in this table were derived from the Schwartz formula for estimating GFR (Schwartz & Gauthier 1985) utilizing child length and stature data published by the CDC.
Adequate Liver Function defined as:

Bilirubin levels ≤ 2.5x ULN for age, and Direct (conjugated) Bilirubin < 0.5 mg/dLSGPT (ALT) ≤ 225 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L.
Subjects who are sexually active must agree to use a medically acceptable method of contraception throughout the entire study period and for 4 weeks after the study is completed. Medically acceptable methods of contraception that may be used by the subject and/or the partner include abstinence, birth control pills or patches, diaphragm and spermicide, condom and vaginal spermicide, surgical sterilization, postmenopausal, vasectomy (>6 months prior to baseline), and progestin implant or injection.
Able to understand and to sign a written informed consent. All subjects and/or their parent or a legally authorized representative must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.

Exclusion Criteria

Have previously received Erwinia asparaginase
Are receiving another investigational agent or will receive an investigational agent in subsequent phases of protocol therapy that include asparaginase
Have a history of ≥ Grade 3 pancreatitis (CTCAE v4.03)
Prior history of a CNS thrombotic event or ≥ Grade 3 (CTCAE v4.03) thrombotic event, excluding catheter-associated clots
Prior history of asparaginase-associated ≥ Grade 3 (CTCAE v4.03) hemorrhagic event or asparaginase-associated thrombus requiring anticoagulation therapy
Blood triglyceride levels > 500 mg/dL or > 5.6 mmol/L
Hyperglycemia requiring insulin therapy
QTc prolongation ≥ 550 msec
Subjects who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study
Subjects who have any serious active disease or co-morbid medical condition (according to investigator's decision), or psychiatric illness that would prevent the subject from signing the informed consent form, assent form or informed consent form by parents, pending institutional requirements, or per investigator's opinion, would prevent the subject from completing one course of pegcrisantaspase.

Pregnant or lactating females or females of childbearing potential not willing to use an adequate method of birth control for the duration of the study. Female subjects who are lactating who do not agree to stop breast-feeding.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Pegcrisantaspase	pegcrisantaspase	-

Primary Outcome Measures

Name	Time	Method
The Response Rate in Children & Young Adults With ALL/LBL and Hypersensitivity to Pegaspargase Defined as the Proportion of Subjects Having a Serum Asparaginase Activity (SAA) Level of >= 0.1 IU/mL Following the First IV Dose in Course 1	15 days during Course 1
The Serum Asparaginase Activity 14 Days After the First Infusion of Study Drug and the Adverse Events in All Participants.	1 Year

Secondary Outcome Measures

Name	Time	Method
The Pharmakokinetic (PK) Profile of IV Pegcrisantaspase in Children and Young Adults With ALL/LBL and Hypersensitivity to Pegaspargase. Pharmakokinetic Profiles to be Assessed Are: Half Life, Elimination Rate, Tmax, Cmax, AUC.	14 Days
The SAA Levels Over Time Following Repeated Administration in Children and Young Adults ALL/LBL and Hypersensitivity to Pegaspargase	30 Days
The Immunogenicity of IV Pegcristaspase by Testing Anti-pegcrisantaspase and Anti-PEG Binding and Neutralizing Antibodies	30 Days

Trial Locations

Locations (43): Johns Hopkins University
🇺🇸
Baltimore, Maryland, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
🇺🇸
Chicago, Illinois, United States
Arkansas Children's Hospital
🇺🇸
Little Rock, Arkansas, United States
All Children's Hospital
🇺🇸
St. Petersburg, Florida, United States
Children's Hospital of Orange County
🇺🇸
Orange, California, United States
Children's Hospital Main Campus
🇺🇸
New Orleans, Louisiana, United States
University of Mississippi Medical Center
🇺🇸
Jackson, Mississippi, United States
University of Minnesota Medical Center - Fairview
🇺🇸
Minneaplois, Minnesota, United States
Bi-Lo Charities Children's Cancer Center
🇺🇸
Greenville, South Carolina, United States
Children's Hospital of Los Angeles
🇺🇸
Los Angeles, California, United States
Miller Children's Hospital
🇺🇸
Long Beach, California, United States
Penn State Children's Hospital
🇺🇸
Hershey, Pennsylvania, United States
Hackensack University Medical Center
🇺🇸
Hackensack, New Jersey, United States
Children's Hospital Central California
🇺🇸
Madera, California, United States
Kaiser Permanente
🇺🇸
Oakland, California, United States
Children's National Medical Center Center for Cancer & Blood Disorders
🇺🇸
Washington, District of Columbia, United States
Washington University School of Medicine
🇺🇸
St. Louis, Missouri, United States
The Steven and Alexandra Cohen Children's Medical Center of New York
🇺🇸
New Hyde Park, New York, United States
Rutgers Cancer Institute of New Jersey
🇺🇸
New Brunswick, New Jersey, United States
The University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma, Oklahoma, United States
Children's Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
Dell Children's Medical Center
🇺🇸
Austin, Texas, United States
Seattle Children's Hospital
🇺🇸
Seatlle, Washington, United States
University of Wisconsin / American Family Children's Hospital
🇺🇸
Madison, Wisconsin, United States
Carolinas Medical Center, Levine Cancer Institute, Levine Children's Hospital
🇺🇸
Charlotte, North Carolina, United States
The University of Texas Southwestern Medical Center
🇺🇸
Dallas, Texas, United States
Nemours Children's Clinic
🇺🇸
Jacksonville, Florida, United States
Nationwide Children's Hospital
🇺🇸
Columbus, Ohio, United States
UCSF Benioff Children's Hospital / UCSF Benioff Children's Hospital
🇺🇸
San Francisco, California, United States
Children's Hospital Colorado
🇺🇸
Aurora, Colorado, United States
Riley Hospital for Children / Indiana University
🇺🇸
Indianapolis, Indiana, United States
Kosair Children's Hospital
🇺🇸
Louisville, Kentucky, United States
C.S. Mott / University of Michigan
🇺🇸
Ann Arbor, Michigan, United States
Wayne State University c/o Children's Hospital of Michigan
🇺🇸
Detroit, Michigan, United States
Children's Hospitals & Clinics of Minnesota
🇺🇸
Minneapolis, Minnesota, United States
Children's Mercy Hospital - Kansas City
🇺🇸
Kansas City, Missouri, United States
Children's Hospital & Medical Center of Omaha
🇺🇸
Omaha, Nebraska, United States
University of North Carolina at Chapel Hill
🇺🇸
Chapel Hill, North Carolina, United States
Cincinnati Children's Hospital Medical
🇺🇸
Cincinnati, Ohio, United States
Phoenix Children's Hospital
🇺🇸
Phoenix, Arizona, United States
Vanderbilt University Ingram Cancer Center
🇺🇸
Nashville, Tennessee, United States
Texas Children's Hospital / Baylor College of Medicine
🇺🇸
Houston, Texas, United States
Children's Hospital of Wisconsin / Midwest Children's Cancer Center
🇺🇸
Milwaukee, Wisconsin, United States