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)

Acute Lymphoblastic Leukemia Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02257684
• Other study ID #: 13-011
• Status: Terminated
• Phase: Phase 2
• First received: September 22, 2014
• Last updated: January 6, 2016
• Start date: September 2014
• Est. completion date: September 2016

Study information

• Verified date: February 2015
• Source: Jazz Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: September 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 21 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Hypersensitivity
• Leukemia
• Leukemia, Lymphoid
• Lymphoblastic Lymphoma
• Lymphoma
• Lymphoma, Non-Hodgkin
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• pegcrisantaspase

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Jazz Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		14 days	No
Primary	The serum asparaginase activity 14 days after the first infusion of study drug and the adverse events in all participants.		1 Year	Yes
Secondary	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	No
Secondary	The SAA levels over time following repeated administration in children and young adults ALL/LBL and hypersensitivity to pegaspargase		30 Days	No
Secondary	The immunogenicity of IV pegcristaspase by testing anti-pegcrisantaspase and anti-PEG binding and neutralizing antibodies		30 Days	Yes