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)

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).

Study Overview

• Status: Terminated
• Conditions: Acute Lymphoblastic Leukemia; Lymphoblastic Lymphoma
• Intervention / Treatment: Drug: pegcrisantaspase

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.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital
  • California
    • Long Beach, California, United States, 9080
      • Miller Children's Hospital
    • Los Angeles, California, United States, 90027-6016
      • Children's Hospital of Los Angeles
    • Madera, California, United States, 93636
      • Children's Hospital Central California
    • Oakland, California, United States, 94611
      • Kaiser Permanente
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
    • San Francisco, California, United States, 94143
      • UCSF Benioff Children's Hospital / UCSF Benioff Children's Hospital
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center Center for Cancer & Blood Disorders
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic
    • St. Petersburg, Florida, United States, 33701
      • All Children's Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children / Indiana University
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Kosair Children's Hospital
  • Louisiana
    • New Orleans, Louisiana, United States, 70118
      • Children's Hospital Main Campus
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • Johns Hopkins University
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5718
      • C.S. Mott / University of Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University c/o Children's Hospital of Michigan
  • Minnesota
    • Minneaplois, Minnesota, United States, 55455
      • University of Minnesota Medical Center - Fairview
    • Minneapolis, Minnesota, United States, 55404
      • Children's Hospitals & Clinics of Minnesota
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital - Kansas City
    • St. Louis, Missouri, United States, 37212
      • Washington University School of Medicine
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Children's Hospital & Medical Center of Omaha
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University 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
      • The Steven and Alexandra Cohen Children's Medical Center of New York
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina At Chapel Hill
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center, Levine Cancer Institute, Levine Children's Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Oklahoma
    • Oklahoma, Oklahoma, United States, 73104
      • The University of Oklahoma Health Sciences Center
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Children's Hospital
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • South Carolina
    • Greenville, South Carolina, United States, 29681
      • BI-LO Charities Children's Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Ingram Cancer Center
  • Texas
    • Austin, Texas, United States, 78723
      • Dell Children's Medical Center
    • Dallas, Texas, United States, 75390
      • The University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital / Baylor College of Medicine
  • Washington
    • Seatlle, Washington, United States, 98105
      • Seattle Children's Hospital
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin / American Family Children's Hospital
    • Milwaukee, Wisconsin, United States, 53226
      • Children's Hospital of Wisconsin / Midwest Children's Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Have a diagnosis of ALL/LBL
2. Be > 1 to ≤ 21 years of age at study enrollment
3. Have had a ≥ Grade 2 allergic reaction (Common Terminology Criteria for Adverse Events [CTCAE] v4.03) to pegaspargase
4. Have ≥ 1 dose(s) of pegaspargase remaining in his/her treatment plan
5. Have a documented SAA level that is below the limit of quantitation per the analytical method.
6. 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.

7. Subjects must have a performance status corresponding to:

   • Karnofsky ≥ 50 (for subjects > 16 years of age)
   • Lansky ≥ 50 (for subjects ≤ 16 years of age)

8. 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.

9. 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.

10. 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.
11. 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:

1. Have previously received Erwinia asparaginase
2. Are receiving another investigational agent or will receive an investigational agent in subsequent phases of protocol therapy that include asparaginase
3. Have a history of ≥ Grade 3 pancreatitis (CTCAE v4.03)
4. Prior history of a CNS thrombotic event or ≥ Grade 3 (CTCAE v4.03) thrombotic event, excluding catheter-associated clots
5. Prior history of asparaginase-associated ≥ Grade 3 (CTCAE v4.03) hemorrhagic event or asparaginase-associated thrombus requiring anticoagulation therapy
6. Blood triglyceride levels > 500 mg/dL or > 5.6 mmol/L
7. Hyperglycemia requiring insulin therapy
8. QTc prolongation ≥ 550 msec
9. Subjects who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study
10. 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 Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pegcrisantaspase	Drug: pegcrisantaspase

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals
• Investigators: Study Director: Roman Skowronski, MD, PhD, Jazz Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: September 22, 2014
• First Submitted That Met QC Criteria: October 2, 2014
• First Posted (Estimate): October 6, 2014

Study Record Updates

• Last Update Posted (Actual): April 4, 2017
• Last Update Submitted That Met QC Criteria: March 6, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: ALL; LBL
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Hypersensitivity; Leukemia; Lymphoma, Non-Hodgkin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
• Other Study ID Numbers: 13-011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No