An Open-Label Study of JZP-458 (RC-P) in Patients With Acute Lymphoblastic Leukemia (ALL)/Lymphoblastic Lymphoma (LBL)

• Sponsor: Jazz Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04145531
• Collaborator: Children's Oncology Group (COG) (Other)
• Enrollment: 229
• Locations: 74
• Arm: 1
• Actual Duration (Months): 30.5
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is an open-label, multicenter, dose confirmation, and PK study of JZP-458 in patients (of any age) with ALL/LBL who are hypersensitive to E. coli-derived asparaginases (allergic reaction or silent inactivation). This study is designed to assess the tolerability and efficacy of JZP-458 (only in patients who develop hypersensitivity to an E. coli-derived asparaginase), as measured by asparaginase activity.

Condition or Disease	Intervention/Treatment	Phase
Acute Lymphoblastic Leukemia; Lymphoblastic Leukemia	Drug: IM JZP-458; Drug: IV JZP-458	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 229 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Multicenter Study of Recombinant Crisantaspase Produced in Pseudomonas Fluorescens (RC-P) in Patients With Acute Lymphoblastic Leukemia (ALL)/Lymphoblastic Lymphoma (LBL) Following Hypersensitivity to E. Coli-derived Asparaginases
• Actual Study Start Date: Dec 27, 2019
• Actual Primary Completion Date: Jul 13, 2022
• Actual Study Completion Date: Jul 13, 2022

Arms and Interventions

Arm

Intervention/Treatment

Experimental: JZP-458 Part A (IM JZP-458) of the study will have 2 IM cohorts: Cohort 1: a JZP-458 repeat dose/confirmatory cohort; a final IM JZP-458 dose level will be selected, and Cohort 2: an expansion cohort to confirm the efficacy and safety of the final IM JZP-458 dose level and schedule Part B (IV JZP-458 Dose Confirmation) will be conducted to define the optimal dose of the IV administration of JZP-458 for further study in ALL/LBL patients as a repeated dose. Additional courses of JZP-458 (IM or IV depending on patient's allocation at study enrollment) will be administered based on each patient's original treatment plan for as long as the patient derives clinical benefit.

Drug: IM JZP-458; IM JZP-458 will be administered in Part A, Cohorts 1 & 2; Drug: IV JZP-458; IV JZP-458 will be administered in Part B

Outcome Measures

Primary Outcome Measures

1. Response Rate During the First Course of IM JZP-458 [2 weeks]

   The response rate is defined as the proportion of patients with the last 72-hour NSAA level ≥ 0.1 IU/mL during the first course of IM JZP-458.

2. Occurrence of treatment-emergent adverse events (TEAEs) [Up to 30 days after last dose]

Secondary Outcome Measures

1. Proportion of patients with the last 48-hour NSAA level ≥ 0.1 IU/mL during the first course of IM administration of JZP-458 [2 weeks]

   For patients in Part A

2. Proportion of patients with the last 48-hour NSAA level ≥ 0.4 IU/mL during the first course of IM administration of JZP-458 [2 weeks]

   For patients in Part A

3. Proportion of patients with the last 72-hour NSAA level ≥ 0.4 IU/mL during the first course of IM administration of JZP-458 [2 weeks]

   For patients in Part A

4. JZP-458 Pharmacokinetics [Up to 30 days after last dose]

   For patients in Part A. Serum asparaginase activity levels after Course 1 (6 doses), then after each subsequent Courses during a patient's treatment plan.

5. Incidence of anti-drug antibody formation against JZP-458 [Up to 30 days after last dose]

   For patients in Part A

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Pediatric and adult patients with a diagnosis of ALL or LBL.

2. Have had an allergic reaction to a long-acting E. coli-derived asparaginase OR have silent inactivation.

3. Have 1 or more courses of E. coli-derived asparaginase remaining in his/her treatment plan.

4. Patients must have, in the opinion of the Investigator, fully recovered from their prior allergic reaction to E. coli-derived asparaginase.

Exclusion Criteria:

1. Have previously received asparaginase Erwinia chrysanthemi or JZP-458.

2. Have relapsed ALL or LBL.

3. Are concurrently receiving another investigational agent and/or treated with an investigational device at the same time as JZP-458 (within 48 hours) during Course 1 of JZP-458.

4. Have a history of ≥ Grade 3 pancreatitis.

5. Prior history of asparaginase-associated ≥ Grade 3 hemorrhagic event or asparaginase-associated thrombus requiring anticoagulation therapy, excluding catheter-related thrombotic events.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's of Alabama	Birmingham	Alabama	United States	35233
2	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016
3	Arkansas Children's Hospital	Little Rock	Arkansas	United States	72202
4	Kaiser Permanente - Orange County - Anaheim Medical Center	Anaheim	California	United States	92806
5	Kaiser Permanente - Downey Medical Center	Downey	California	United States	90242
6	Kaiser Permanente - Fontana Medical Center	Fontana	California	United States	92335
7	Loma Linda University Medical Center	Loma Linda	California	United States	92350
8	MemorialCare Miller Children's and Women's Hospital Long Beach	Long Beach	California	United States	90806
9	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
10	Kaiser Permanente- Los Angeles Medical Center	Los Angeles	California	United States	90027
11	Benioff Children's Hospital Oakland	Oakland	California	United States	94609
12	Kaiser Permanente - Oakland Medical Center	Oakland	California	United States	94611
13	Children's Hospital of Orange County Main Campus - Orange	Orange	California	United States	92868
14	Kaiser Permanente - Roseville Medical Center	Roseville	California	United States	95661
15	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
16	Kaiser Permanente - San Diego Medical Center	San Diego	California	United States	92120
17	University of California San Francisco Benioff Children's Hospital - Mission Bay	San Francisco	California	United States	94158
18	Kaiser Permanente - Santa Clara Medical Center	Santa Clara	California	United States	95051
19	Connecticut Children's Medical Center	Hartford	Connecticut	United States	06106
20	Smilow Cancer Hospital - New Haven	New Haven	Connecticut	United States	06511
21	Nemours Alfred I. Dupont Hospital for Children	Wilmington	Delaware	United States	19803
22	Children's National Health System	Washington	District of Columbia	United States	20010
23	Golisano Children's Hospital of Southwest Florida	Fort Myers	Florida	United States	33908
24	Memorial Medical Office Centre	Hollywood	Florida	United States	33021
25	Nemours Children's Specialty Care Jacksonville	Jacksonville	Florida	United States	32207
26	AdventHealth Orlando	Orlando	Florida	United States	32803
27	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida	United States	33701
28	Scottish Rite Hospital	Atlanta	Georgia	United States	30342
29	Kapi'olani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
30	Ann and Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
31	Norton Children's Hospital	Louisville	Kentucky	United States	40202
32	Dana-Farber/Boston Children's Cancer and Blood Disorders Center	Boston	Massachusetts	United States	02215
33	C.S. Mott Children's Hospital	Ann Arbor	Michigan	United States	48109
34	Children's Minnesota	Minneapolis	Minnesota	United States	55404
35	Masonic Cancer Center	Minneapolis	Minnesota	United States	55455
36	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
37	Washington University School of Medicine in Saint Louis	Saint Louis	Missouri	United States	63110
38	Alliance for Childhood Diseases	Las Vegas	Nevada	United States	89135
39	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
40	Morristown Medical Center	Morristown	New Jersey	United States	07960
41	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
42	Cohen Children's Medical Center	New Hyde Park	New York	United States	11040
43	NYU - Stephen D. Hassenfeld Children's Center for Cancer and Blood Disorders	New York	New York	United States	10016
44	Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
45	Memorial Sloan-Kettering Cancer Center - New York	New York	New York	United States	10065
46	Wake Forest Baptist Health	Winston-Salem	North Carolina	United States	27157
47	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
48	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
49	The Children's Hospital at Oklahoma University Medical Center	Oklahoma City	Oklahoma	United States	73104
50	Oregon Health and Science University	Portland	Oregon	United States	97201
51	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
52	University of Pittsburgh Medical Center - Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15224
53	Neurology Clinic, P.C	Cordova	Tennessee	United States	38018
54	East Tennessee Children's Hospital	Knoxville	Tennessee	United States	37913
55	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
56	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
57	Children's Blood and Cancer Center	Austin	Texas	United States	78723
58	Medical City Dallas Hospital	Dallas	Texas	United States	75230
59	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
60	Texas Children's Hospital	Houston	Texas	United States	77030
61	Methodist Hospital - San Antonio	San Antonio	Texas	United States	78229
62	Primary Children's Hospital	Salt Lake City	Utah	United States	84113
63	Inova Medical Group - Fairfax Hospital	Falls Church	Virginia	United States	22042
64	Children's Hospital of The King's Daughters	Norfolk	Virginia	United States	23507
65	Massey Cancer Center	Richmond	Virginia	United States	23220
66	Seattle Children's Hospital	Seattle	Washington	United States	98105
67	Providence Sacred Heart Medical Center	Spokane	Washington	United States	99204
68	CancerCare Manitoba - McDermot and Urgent Care Site	Winnipeg	Manitoba	Canada	R3E 0V9
69	McMaster Children's Hospital	Hamilton	Ontario	Canada	L8N 3Z5
70	Victoria Hospital & Children's Hospital	London	Ontario	Canada	N6C 2V5
71	Children's Hospital of Eastern Ontario	Ottawa	Ontario	Canada	K1H 8L1
72	SickKids - The Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
73	Centre Hospitalier Universitaire Sainte-Justine	Montréal	Quebec	Canada	H3T 1C5
74	The Montreal Children's Hospital	Montréal	Quebec	Canada	H4A 3J1

Sponsors and Collaborators

• Jazz Pharmaceuticals
• Children's Oncology Group (COG)

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jazz Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04145531
• Other Study ID Numbers: JZP458-201; AALL1931
• First Posted: Oct 30, 2019
• Last Update Posted: Aug 5, 2022
• Last Verified: Aug 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Jazz Pharmaceuticals: ALL; LBL; Asparaginase; Leukemia; Childhood acute lymphoblastic leukemia
• Additional relevant MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid

Study Results

No Results Posted as of Aug 5, 2022