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)

• Sponsor: Jazz Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02257684
• Collaborator: (none)
• Enrollment: 4
• Locations: 43
• Arm: 1
• Duration (Months): 16
• Patients Per Site: 0.1
• Patients Per Site Per Month: 0

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Acute Lymphoblastic Leukemia; Lymphoblastic Lymphoma	Drug: pegcrisantaspase	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Sep 1, 2014
• Actual Primary Completion Date: Feb 1, 2015
• Actual Study Completion Date: Jan 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pegcrisantaspase	Drug: pegcrisantaspase

Outcome Measures

Primary Outcome Measures

1. 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]

2. 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

1. 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]

2. The SAA Levels Over Time Following Repeated Administration in Children and Young Adults ALL/LBL and Hypersensitivity to Pegaspargase [30 Days]

3. The Immunogenicity of IV Pegcristaspase by Testing Anti-pegcrisantaspase and Anti-PEG Binding and Neutralizing Antibodies [30 Days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

1. 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.

1. 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.

1. 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.

2. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016
2	Arkansas Children's Hospital	Little Rock	Arkansas	United States	72202
3	Miller Children's Hospital	Long Beach	California	United States	9080
4	Children's Hospital of Los Angeles	Los Angeles	California	United States	90027-6016
5	Children's Hospital Central California	Madera	California	United States	93636
6	Kaiser Permanente	Oakland	California	United States	94611
7	Children's Hospital of Orange County	Orange	California	United States	92868
8	UCSF Benioff Children's Hospital / UCSF Benioff Children's Hospital	San Francisco	California	United States	94143
9	Children's Hospital Colorado	Aurora	Colorado	United States	80045
10	Children's National Medical Center Center for Cancer & Blood Disorders	Washington	District of Columbia	United States	20010
11	Nemours Children's Clinic	Jacksonville	Florida	United States	32207
12	All Children's Hospital	St. Petersburg	Florida	United States	33701
13	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
14	Riley Hospital for Children / Indiana University	Indianapolis	Indiana	United States	46202
15	Kosair Children's Hospital	Louisville	Kentucky	United States	40202
16	Children's Hospital Main Campus	New Orleans	Louisiana	United States	70118
17	Johns Hopkins University	Baltimore	Maryland	United States	21218
18	C.S. Mott / University of Michigan	Ann Arbor	Michigan	United States	48109-5718
19	Wayne State University c/o Children's Hospital of Michigan	Detroit	Michigan	United States	48201
20	University of Minnesota Medical Center - Fairview	Minneaplois	Minnesota	United States	55455
21	Children's Hospitals & Clinics of Minnesota	Minneapolis	Minnesota	United States	55404
22	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
23	Children's Mercy Hospital - Kansas City	Kansas City	Missouri	United States	64108
24	Washington University School of Medicine	St. Louis	Missouri	United States	37212
25	Children's Hospital & Medical Center of Omaha	Omaha	Nebraska	United States	68114
26	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
27	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
28	The Steven and Alexandra Cohen Children's Medical Center of New York	New Hyde Park	New York	United States	11040
29	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
30	Carolinas Medical Center, Levine Cancer Institute, Levine Children's Hospital	Charlotte	North Carolina	United States	28203
31	Cincinnati Children's Hospital Medical	Cincinnati	Ohio	United States	45229
32	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
33	The University of Oklahoma Health Sciences Center	Oklahoma	Oklahoma	United States	73104
34	Penn State Children's Hospital	Hershey	Pennsylvania	United States	17033
35	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
36	Bi-Lo Charities Children's Cancer Center	Greenville	South Carolina	United States	29681
37	Vanderbilt University Ingram Cancer Center	Nashville	Tennessee	United States	37212
38	Dell Children's Medical Center	Austin	Texas	United States	78723
39	The University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
40	Texas Children's Hospital / Baylor College of Medicine	Houston	Texas	United States	77030
41	Seattle Children's Hospital	Seatlle	Washington	United States	98105
42	University of Wisconsin / American Family Children's Hospital	Madison	Wisconsin	United States	53792
43	Children's Hospital of Wisconsin / Midwest Children's Cancer Center	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• Jazz Pharmaceuticals

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jazz Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02257684
• Other Study ID Numbers: 13-011
• First Posted: Oct 6, 2014
• Last Update Posted: Apr 4, 2017
• Last Verified: Mar 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Jazz Pharmaceuticals: ALL; LBL
• Additional relevant MeSH terms: Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Hypersensitivity

Study Results

Participant Flow

Arm/Group Title	Pegcrisantaspase
Arm/Group Description	IV administration of pegcrisantaspase in Course 1
Period Title: Overall Study
STARTED	4
COMPLETED	0
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Pegcrisantaspase
Arm/Group Description	pegcrisantaspase
Overall Participants	4
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	12.95
Sex: Female, Male (Count of Participants)
Female	1 25%
Male	3 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 25%
Not Hispanic or Latino	3 75%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	4 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	4 100%

Outcome Measures

1. Primary Outcome

Title	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
Time Frame	15 days during Course 1

Outcome Measure Data

Analysis Population Description

Only 1 of the first 4 patients dosed achieved the predefined serum asparaginase activity (SAA) level above the 0.1 IU/mL therapeutic threshold 14 days following the first IV pegcrisantaspase dose in Course 1 (Primary Objective of the study).

Arm/Group Title	Pegcrisantaspase
Arm/Group Description	IV administration of pegcrisantaspase in Course 1
Measure Participants	1
Course 1; Day 0 (Screening)	0.013
Course 1; Day 1 (Pre-dose)	0.013
Course 1; Day 1 (1 hour post)	0.50
Course 1; Day 1 (3 hour post)	0.44
Course 1; Day 1 (5 hour post)	0.41
Course 1; Day 2 (Visit 2)	0.36
Course 1; Day 8 (Visit 3)	0.28
Course 1; Day 11 (Visit 4)	0.24
Course 1; Day 15 (Visit 5)	0.26

2. Primary Outcome

Title	The Serum Asparaginase Activity 14 Days After the First Infusion of Study Drug and the Adverse Events in All Participants.
Time Frame	1 Year

Outcome Measure Data

Analysis Population Description

Not Applicable, as the study was terminated before this endpoint was analyzed.

Arm/Group Title	Pegcrisantaspase
Arm/Group Description	IV administration of pegcrisantaspase in Course 1
Measure Participants	0
	0

3. Secondary Outcome

Title	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.
Time Frame	14 Days

Outcome Measure Data

Analysis Population Description

Not Applicable, as the study was terminated before this endpoint was analyzed.

Arm/Group Title	Pegcrisantaspase
Arm/Group Description	IV administration of pegcrisantaspase in Course 1
Measure Participants	0
	0

4. Secondary Outcome

Title	The SAA Levels Over Time Following Repeated Administration in Children and Young Adults ALL/LBL and Hypersensitivity to Pegaspargase
Time Frame	30 Days

Outcome Measure Data

Analysis Population Description

Not Applicable, as the study was terminated before this endpoint was analyzed.

Arm/Group Title	Pegcrisantaspase
Arm/Group Description	IV administration of pegcrisantaspase in Course 1
Measure Participants	0
	0

5. Secondary Outcome

Title	The Immunogenicity of IV Pegcristaspase by Testing Anti-pegcrisantaspase and Anti-PEG Binding and Neutralizing Antibodies
Time Frame	30 Days

Outcome Measure Data

Analysis Population Description

Not Applicable, as the study was terminated before this endpoint was analyzed.

Arm/Group Title	Pegcrisantaspase
Arm/Group Description	IV administration of pegcrisantaspase in Course 1
Measure Participants	0
	0

Adverse Events

Arm/Group Title	Pegcrisantaspase
Arm/Group Description	IV administration of pegcrisantaspase in Course 1
All Cause Mortality
	Pegcrisantaspase
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Pegcrisantaspase
	Affected / at Risk (%)	# Events
Total	3/4 (75%)
Blood and lymphatic system disorders
Febrile neutropenia	1/4 (25%)
Pancytopenia	1/4 (25%)
General disorders
Pyrexia	1/4 (25%)
Immune system disorders
Anaphylactic reaction	1/4 (25%)
Injury, poisoning and procedural complications
Infusion related reaction	1/4 (25%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
T-cell lymphoma recurrent	1/4 (25%)
Other (Not Including Serious) Adverse Events
	Pegcrisantaspase
	Affected / at Risk (%)	# Events
Total	3/4 (75%)
Blood and lymphatic system disorders
Anaemia	2/4 (50%)
Neutropenia	1/4 (25%)
Eye disorders
Periorbital oedema	1/4 (25%)
General disorders
Mucosal inflammation	1/4 (25%)
Investigations
Alanine aminotransferase increased	1/4 (25%)
Platelet count decreased	1/4 (25%)
Musculoskeletal and connective tissue disorders
Muscle spasms	1/4 (25%)
Nervous system disorders
Headache	1/4 (25%)
Respiratory, thoracic and mediastinal disorders
Nasal congestion	1/4 (25%)
Rhinorrhoea	1/4 (25%)
Skin and subcutaneous tissue disorders
Alopecia	1/4 (25%)

Limitations/Caveats

Only 1 patient achieved the predefined SAA level above the 0.1 IU/mL therapeutic threshold 14 days following IV pegcrisantaspase dose in Course 1. Therefore, the corresponding PK parameters for repeated administration were not calculated.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.