ch14.18 Pharmacokinetic Study in High-risk Neuroblastoma

Phase 1

Completed

Interventions: Biological: ch14.18 -NCI
Biological: ch14.18-UTC
Biological: Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)
Biological: Aldesleukin (IL-2)
Drug: Isotretinoin

Brief Summary: The purpose of this study is to compare the pharmacokinetics (blood levels) and safety of chimeric (ch) 14.18 manufactured by two independent drug makers (United Therapeutics \[UTC\] or the National Cancer Institute \[NCI\]).

Detailed Description: This is a multi-center, randomized, open-label, two-sequence, cross-over study for eligible subjects with high-risk neuroblastoma to assess the comparability of ch14.18 manufactured with UTC drug product and ch14.18 manufactured with NCI drug product. Subjects will be randomly allocated to receive ch14.18 manufactured by UTC or NCI during Courses 1 and 2 followed by ch14.18 manufactured by other manufacturer (UTC or NCI) during Courses 3, 4, and 5.

Recruitment & Eligibility

Inclusion Criteria

Diagnosis of high-risk neuroblastoma
8 years of age or younger at diagnosis of high-risk neuroblastoma
Patients must have completed therapy including intensive induction followed by autologous stem cell transplantation (ASCT) and radiotherapy

* Radiotherapy may be waived for patients who either have small adrenal masses which are completely resected up front, or who never have an identifiable primary tumor
Must meet the International Neuroblastoma Response Criteria (INRC) for CR, VGPR, or PR for primary site, soft tissue metastases, and bone metastases AND must also meet the protocol specified criteria for bone marrow response as follows:

* No more than 10% tumor (of total nucleated cellular content) seen on any specimen from a bilateral bone marrow aspirate/biopsy
Patient who have no tumor seen on the prior bone marrow, and then have ≤ 10% tumor on any of the bilateral marrow aspirate/biopsy specimens done at pre-ASCT and/or pre-enrollment evaluation will also be eligible
No more than 12 months from starting the first induction chemotherapy after diagnosis to the date of ASCT

* For patients who became high-risk neuroblastoma after initial non-high risk disease, the 12 months period should start from the date of induction therapy for high-risk neuroblastoma to the date of ASCT
No progressive disease at time of registration except for protocol-specified bone marrow response
Adequate hematological, renal, hepatic, pulmonary and cardiac function
CNS toxicity < Grade 2

Exclusion Criteria

Arm && Interventions

Group	Intervention	Description
Sequence 2	ch14.18 -NCI	NCI ch14.18 for two courses and UTC ch14.18 for three courses
Sequence 2	Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)	NCI ch14.18 for two courses and UTC ch14.18 for three courses
Sequence 1	ch14.18 -NCI	UTC ch14.18 for two courses and NCI ch14.18 for three courses
Sequence 1	ch14.18-UTC	UTC ch14.18 for two courses and NCI ch14.18 for three courses
Sequence 1	Aldesleukin (IL-2)	UTC ch14.18 for two courses and NCI ch14.18 for three courses
Sequence 2	ch14.18-UTC	NCI ch14.18 for two courses and UTC ch14.18 for three courses
Sequence 2	Aldesleukin (IL-2)	NCI ch14.18 for two courses and UTC ch14.18 for three courses
Sequence 1	Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)	UTC ch14.18 for two courses and NCI ch14.18 for three courses
Sequence 1	Isotretinoin	UTC ch14.18 for two courses and NCI ch14.18 for three courses
Sequence 2	Isotretinoin	NCI ch14.18 for two courses and UTC ch14.18 for three courses

Primary Outcome Measures

Name	Time	Method
Peak Plasma Concentration (Cmax)	PK samples obtained during Courses 1 and 3: Days 0, 3, 4, 5, 6, 7, 9, 10, 11, 14, 15, 16, 17; PK samples obtained during Courses 2 and 4: Days 0, 7, 10; End of Treatment	Twenty-two PK samples will be obtained at the following timepoints: Courses 1 and 3: Day: 0 Days: 3, 4, 5 and 6: post ch14.18 Days 7:10 to 14 hours post ch14.18 Days 9 to 11: Single sample Days 14 to 17: Single sample Courses 2 and 4: Day 0: Pre-IL-2 Day 7: Pre-ch14.18 Day 10 (Course 4 only): Post ch14.18 End of Treatment: Within 2 weeks post isotretinoin
Area Under the Plasma Concentration Curve (AUC)	PK samples obtained during Courses 1 and 3: Days 0, 3, 4, 5, 6, 7, 9, 10, 11, 14, 15, 16, 17; PK samples obtained during Courses 2 and 4: Days 0, 7, 10; End of Treatment	Twenty-two PK samples will be obtained at the following timepoints: Courses 1 and 3: Day: 0 Days: 3, 4, 5 and 6: post ch14.18 Days 7:10 to 14 hours post ch14.18 Days 9 to 11: Single sample Days 14 to 17: Single sample Courses 2 and 4: Day 0: Pre-IL-2 Day 7: Pre-ch14.18 Day 10 (Course 4 only): Post ch14.18 End of Treatment: Within 2 weeks post isotretinoin

Secondary Outcome Measures

Name	Time	Method

Locations (13): Children's Hospital of Los Angeles
🇺🇸
Los Angeles, California, United States
Children's Healthcare of Atlanta - Egleston
🇺🇸
Atlanta, Georgia, United States
Children's Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
🇺🇸
Minneapolis, Minnesota, United States
Seattle Children's Hospital
🇺🇸
Seattle, Washington, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
The University of Chicago
🇺🇸
Chicago, Illinois, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
University of Michigan C.S. Mott Children's Hospital
🇺🇸
Ann Arbor, Michigan, United States
Children's Mercy Hospital (Kansas)
🇺🇸
Kansas, Missouri, United States
Washington University School of Medicine
🇺🇸
St. Louis, Missouri, United States
Columbia University Medical Center
🇺🇸
New York, New York, United States
Cook Children's Medical Center
🇺🇸
Fort Worth, Texas, United States