A Study of Erwinaze Administered Intravenously in Patients Who Had an Allergy to Frontline Asparaginase Therapy

• Sponsor: Jazz Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01643408
• Collaborator: (none)
• Enrollment: 30
• Locations: 22
• Arm: 1
• Duration (Months): 13
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will utilize Erwinaze via intravenous administration in patients between the ages of 1 and 30 who have experienced an allergy to their frontline therapy. The study will determine the proportion of patients with 2 day nadir serum asparaginase activity levels that are >0.1 IU/mL during the first 2 weeks of treatment with 3 times per week IV dosing.

Condition or Disease	Intervention/Treatment	Phase
Acute Lymphoblastic Leukemia; Lymphoblastic Lymphoma	Drug: asparaginase Erwinia chrysanthemi	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II, An Open Label, Single Arm, Multi-Center Pharmacokinetic Study of Intravenous Erwinaze (Asparaginase Erwinia Chrysanthemi)Following Allergy to Native E. Coli Asparaginase (Elspar or Kidrolase), Pegaspargase (Oncaspar) or Calaspargase Pegol (EZN-2285) in Children, Adolescents and Young Adults With Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma.
• Study Start Date: Nov 1, 2012
• Actual Primary Completion Date: Aug 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Open-Label Erwinaze	Drug: asparaginase Erwinia chrysanthemi

Outcome Measures

Primary Outcome Measures

1. Two Day Nadir Serum Asparaginase Activity (NSAA) Level [48 hours post-dose 5]

   To report the mean 2 day NSAA levels (48 hour levels taken after the 5th dose) that are > or = 0.1 IU/mL during the first 2 weeks of treatment with 3-times per week intravenous dosing of Erwinase at 25,000 IU/m2/dose.

Secondary Outcome Measures

1. Proportion of Participants Achieving Sustained NSAA Values of >0.1 U/mL at 48 Hours [48 hours post-dose 5]

   To report the proportion of participants achieving 2 day NSAA levels (48 hour levels taken after the 5th dose) that are > or = 0.1 IU/mL during the first 2 weeks of treatment with 3-times per week intravenous dosing of Erwinase at 25,000 IU/m2/dose.

2. Three Day NSAA Level [72 hours post-dose 6]

   To report the mean 3 day NSAA levels (72 hour levels taken after the 6th dose) that are > or = 0.1 IU/mL in the first 2 weeks of treatment with 3 times per week intravenous dosing of Erwinase at 25,000 IU/m2/dose.

3. Proportion of Participants Achieving Sustained NSAA Values of >0.1 U/mL at 72 Hours [72 hours post-dose 6]

   To report the proportion of participants achieving 3 day NSAA levels (72 hour levels taken after the 6th dose) that are > or = 0.1 IU/mL in the first 2 weeks of treatment with 3 times per week intravenous dosing of Erwinase at 25,000 IU/m2/dose.

4. Nadir Serum Asparaginase Activity Over Time [4 weeks to 30 weeks]

   To describe the NSAA over time in participants with ALL/Lymphoblastic Lymphoma who have/had developed hypersensitivity to native E. coli asparaginase, Pegaspargase or Calaspargase pegol and are receiving intravenous Erwinaze 3 times per week for a prolonged duration (4-30 weeks).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 30 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma,

• Ages >/= 1 and </= to 30 years at the time of initial diagnosis

• Undergoing asparaginase treatment for ALL or lymphoblastic lymphoma

• Documented Grade 2 or higher hypersensitivity reaction to native or pegylated E. coli asparaginase or Calaspargase pegol

• Must have two remaining weeks of native E. coli asparaginase treatment or 1 remaining dose of either Pegaspargase or Calaspargase pegol

• Direct bilirubin less than or equal to Grade 2

• Amylase and lipase within normal limits (per institutional standards)

• Signed informed consent by the patient is greater than or equal to 18 years or by the parent if the patient is younger than 18 years old.

Exclusion Criteria:

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Los Angeles	Los Angeles	California	United States	90027
2	Children's Hospital of Orange County	Orange County	California	United States	92868
3	Stanford Medical Center	Palo Alto	California	United States	94304
4	Children's Hospital	Aurora	Colorado	United States	80045
5	All Children's Hospital	Saint Petersburg	Florida	United States	33701
6	Children's Memorial Hospital	Chicago	Illinois	United States	60611
7	John Hopkins	Baltimore	Maryland	United States	21231
8	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
9	University of Minnesota	Minneapolis	Michigan	United States	55455
10	Children's Hospital and Clinics of Minnesota	Minneapolis	Minnesota	United States	55406
11	UMDNJ/Robert Wood Johnson	New Brunswick	New Jersey	United States	08903
12	Montifiore Medical Center	Bronx	New York	United States	10467
13	Columbia Presbyterian Medical Center	New York	New York	United States	10032
14	Oregon Health & Sciences	Portland	Oregon	United States	97239
15	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15224
16	Texas Children's Hospital	Houston	Texas	United States	77030
17	Inova Fairfax Medical Center	Falls Church	Virginia	United States	22042
18	Children's Hospital of Wisconsin	Milwaukee	Wisconsin	United States	53226
19	McMasters University Medical Center	Hamilton	Ontario	Canada	L8S4R1
20	Sick Children's Hospital	Toronto	Ontario	Canada	m561X8
21	Hospital St. Justine	Saint Catherine	Quebec	Canada	H3T1CS
22	Quebec Children's Hospital	Sainte-Foy	Quebec	Canada	CIV462

Sponsors and Collaborators

• Jazz Pharmaceuticals

Investigators

• Principal Investigator: Lynda Vrooman, MD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jazz Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01643408
• Other Study ID Numbers: 100EUSA12
• First Posted: Jul 18, 2012
• Last Update Posted: Jun 23, 2021
• Last Verified: Jun 1, 2021

• Keywords provided by Jazz Pharmaceuticals: Acute Lymphoblastic Leukemia; Lymphoblastic Lymphoma; Erwinaze; asparaginase; Eusa Pharma; Pharmacokinetic study; NSAA
• Additional relevant MeSH terms: Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Asparaginase

Study Results

Participant Flow

Arm/Group Title	Safety Population
Arm/Group Description	All participants who received at least 1 dose of Erwinaze
Period Title: Overall Study
STARTED	30
COMPLETED	16
NOT COMPLETED	14

Baseline Characteristics

Arm/Group Title	Safety Population
Arm/Group Description	All patients who received at least one dose of Erwinaze
Overall Participants	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	7.9 (5.08)
Sex: Female, Male (Count of Participants)
Female	11 36.7%
Male	19 63.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 3.3%
Asian	2 6.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 3.3%
White	25 83.3%
More than one race	0 0%
Unknown or Not Reported	1 3.3%

Outcome Measures

1. Primary Outcome

Title	Two Day Nadir Serum Asparaginase Activity (NSAA) Level
Description	To report the mean 2 day NSAA levels (48 hour levels taken after the 5th dose) that are > or = 0.1 IU/mL during the first 2 weeks of treatment with 3-times per week intravenous dosing of Erwinase at 25,000 IU/m2/dose.
Time Frame	48 hours post-dose 5

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic (PK) population consisted of all participants who received at least 1 dose of Erwinaze and were considered evaluable.

Arm/Group Title	Open-Label Erwinaze
Arm/Group Description	asparaginase Erwinia chrysanthemi
Measure Participants	24
Mean (Standard Deviation) [(IU/mL)]	0.32 (0.23)

2. Secondary Outcome

Title	Proportion of Participants Achieving Sustained NSAA Values of >0.1 U/mL at 48 Hours
Description	To report the proportion of participants achieving 2 day NSAA levels (48 hour levels taken after the 5th dose) that are > or = 0.1 IU/mL during the first 2 weeks of treatment with 3-times per week intravenous dosing of Erwinase at 25,000 IU/m2/dose.
Time Frame	48 hours post-dose 5

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Open-Label Erwinaze
Arm/Group Description	asparaginase Erwinia chrysanthemi
Measure Participants	24
Count of Participants [Participants]	20 66.7%

3. Secondary Outcome

Title	Three Day NSAA Level
Description	To report the mean 3 day NSAA levels (72 hour levels taken after the 6th dose) that are > or = 0.1 IU/mL in the first 2 weeks of treatment with 3 times per week intravenous dosing of Erwinase at 25,000 IU/m2/dose.
Time Frame	72 hours post-dose 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Open-Label Erwinaze
Arm/Group Description	asparaginase Erwinia chrysanthemi
Measure Participants	21
Mean (Standard Deviation) [(IU/mL)]	0.09 (0.07)

4. Secondary Outcome

Title	Proportion of Participants Achieving Sustained NSAA Values of >0.1 U/mL at 72 Hours
Description	To report the proportion of participants achieving 3 day NSAA levels (72 hour levels taken after the 6th dose) that are > or = 0.1 IU/mL in the first 2 weeks of treatment with 3 times per week intravenous dosing of Erwinase at 25,000 IU/m2/dose.
Time Frame	72 hours post-dose 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Open-Label Erwinaze
Arm/Group Description	asparaginase Erwinia chrysanthemi
Measure Participants	21
Count of Participants [Participants]	9 30%

5. Secondary Outcome

Title	Nadir Serum Asparaginase Activity Over Time
Description	To describe the NSAA over time in participants with ALL/Lymphoblastic Lymphoma who have/had developed hypersensitivity to native E. coli asparaginase, Pegaspargase or Calaspargase pegol and are receiving intravenous Erwinaze 3 times per week for a prolonged duration (4-30 weeks).
Time Frame	4 weeks to 30 weeks

Outcome Measure Data

Analysis Population Description

This population consisted of participants who completed Course 4 with Pharmacokinetic(s) (PK) assessments 48 hours after dose 5 (week 8).

Arm/Group Title	Open-Label Erwinaze
Arm/Group Description	asparaginase Erwinia chrysanthemi
Measure Participants	6
Mean (Standard Deviation) [IU/mL]	0.51 (0.252)

Adverse Events

Time Frame	4 Weeks
Arm/Group Title	Safety Population
Arm/Group Description	All participants who received at least 1 dose of Erwinaze
All Cause Mortality
	Safety Population
	Affected / at Risk (%)	# Events
Total	0/30 (0%)
Serious Adverse Events
	Safety Population
	Affected / at Risk (%)	# Events
Total	15/30 (50%)
Blood and lymphatic system disorders
Febrile Neutropenia	4/30 (13.3%)
Lymphadenitis	1/30 (3.3%)
Cardiac disorders
Sinus Tachycardia	1/30 (3.3%)
Gastrointestinal disorders
Nausea	1/30 (3.3%)
Vomiting	1/30 (3.3%)
Pancreatitis	2/30 (6.7%)
Stomatitis	1/30 (3.3%)
General disorders
Pyrexia	1/30 (3.3%)
Immune system disorders
Hypersensitivity	4/30 (13.3%)
Infections and infestations
Bacteraemia	1/30 (3.3%)
Sepsis	1/30 (3.3%)
Musculoskeletal and connective tissue disorders
Pain In Extremity	1/30 (3.3%)
Nervous system disorders
Transient Ischaemic Attack	1/30 (3.3%)
Posterior Reversible Encephalopathy Syndrome	1/30 (3.3%)
Skin and subcutaneous tissue disorders
Skin Ulcer	1/30 (3.3%)
Urticaria	1/30 (3.3%)
Other (Not Including Serious) Adverse Events
	Safety Population
	Affected / at Risk (%)	# Events
Total	23/30 (76.7%)
Blood and lymphatic system disorders
Febrile Neutropenia	4/30 (13.3%)
Gastrointestinal disorders
Nausea	7/30 (23.3%)
Vomiting	6/30 (20%)
Pancreatitis	2/30 (6.7%)
Stomatitis	2/30 (6.7%)
General disorders
Pyrexia	3/30 (10%)
Immune system disorders
Hypersensitivity	10/30 (33.3%)
Investigations
Alanine Aminotransferase Increased	3/30 (10%)
Metabolism and nutrition disorders
Hyperglycemia	5/30 (16.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The sponsor can review trial results communications prior to public release and can embargo such communications for a period of at least 60 days from the time submitted to sponsor for review. If requested by sponsor, the PI will withhold publication for up to an additional 30 days. Furthermore, the first publication of study results must be a joint publication of all study sites unless a joint manuscript has not been submitted for publication within 12 months of completion of the study.