Clinical trial NCT02257684: 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)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Acute Lymphoblastic Leukemia
Lymphoblastic Lymphoma
Keywords: ALL
LBL
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2014-10-06
Enrollment: 4
Sex: ALL
Minimum age (years): 1
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 15 days during Course 1
measure: The Serum Asparaginase Activity 14 Days After the First Infusion of Study Drug and the Adverse Events in All Participants.
timeFrame: 1 Year
Secondary outcomes:
measure: 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.
timeFrame: 14 Days
measure: The SAA Levels Over Time Following Repeated Administration in Children and Young Adults ALL/LBL and Hypersensitivity to Pegaspargase
timeFrame: 30 Days
measure: The Immunogenicity of IV Pegcristaspase by Testing Anti-pegcrisantaspase and Anti-PEG Binding and Neutralizing Antibodies
timeFrame: 30 Days
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Long Beach
country: United States
facility: Miller Children's Hospital
state: California
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Madera
country: United States
facility: Children's Hospital Central California
state: California
city: Oakland
country: United States
facility: Kaiser Permanente
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: San Francisco
country: United States
facility: UCSF Benioff Children's Hospital / UCSF Benioff Children's Hospital
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center Center for Cancer & Blood Disorders
state: District of Columbia
city: Jacksonville
country: United States
facility: Nemours Children's Clinic
state: Florida
city: St. Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children / Indiana University
state: Indiana
city: Louisville
country: United States
facility: Kosair Children's Hospital
state: Kentucky
city: New Orleans
country: United States
facility: Children's Hospital Main Campus
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Ann Arbor
country: United States
facility: C.S. Mott / University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Wayne State University c/o Children's Hospital of Michigan
state: Michigan
city: Minneaplois
country: United States
facility: University of Minnesota Medical Center - Fairview
state: Minnesota
city: Minneapolis
country: United States
facility: Children's Hospitals & Clinics of Minnesota
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: Children's Mercy Hospital - Kansas City
state: Missouri
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: Children's Hospital & Medical Center of Omaha
state: Nebraska
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: New Hyde Park
country: United States
facility: The Steven and Alexandra Cohen Children's Medical Center of New York
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center, Levine Cancer Institute, Levine Children's Hospital
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Oklahoma
country: United States
facility: The University of Oklahoma Health Sciences Center
state: Oklahoma
city: Hershey
country: United States
facility: Penn State Children's Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Greenville
country: United States
facility: Bi-Lo Charities Children's Cancer Center
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Ingram Cancer Center
state: Tennessee
city: Austin
country: United States
facility: Dell Children's Medical Center
state: Texas
city: Dallas
country: United States
facility: The University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital / Baylor College of Medicine
state: Texas
city: Seatlle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Madison
country: United States
facility: University of Wisconsin / American Family Children's Hospital
state: Wisconsin
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin / Midwest Children's Cancer Center
state: Wisconsin
Study officials:
affiliation: Jazz Pharmaceuticals
name: Roman Skowronski, MD, PhD
role: STUDY_DIRECTOR
References: