ch14.18 Pharmacokinetic Study in High-risk Neuroblastoma
A Comparative Pharmacokinetic and Safety Study of Chimeric Monoclonal Antibody ch14.18 With Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), Interleukin-2 (IL-2) and Isotretinoin in High Risk Neuroblastoma Patients Following Myeloablative Therapy
1 other identifier
interventional
28
1 country
13
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 \[NCI\]).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Aug 2012
13 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 30, 2012
CompletedFirst Posted
Study publicly available on registry
May 4, 2012
CompletedStudy Start
First participant enrolled
August 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2014
CompletedResults Posted
Study results publicly available
September 23, 2015
CompletedSeptember 23, 2015
August 1, 2015
1.8 years
April 30, 2012
June 3, 2015
August 20, 2015
Conditions
Outcome Measures
Primary Outcomes (2)
Area Under the Plasma Concentration Curve (AUC)
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
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
Peak Plasma Concentration (Cmax)
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
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
Study Arms (2)
Sequence 1
EXPERIMENTALUTC ch14.18 for two courses and NCI ch14.18 for three courses
Sequence 2
EXPERIMENTALNCI ch14.18 for two courses and UTC ch14.18 for three courses
Interventions
GM-CSF will be administered SC at a dose of 250 mcg/m\^2/day for 14 days during Courses 1, 3, and 5.
Aldesleukin (IL-2) will be administered IV at a dose of 3 MIU/m\^2/day for the first week and at a dose of 4.5 MIU/m\^2/day for the second week during Courses 2 and 4.
Isotretinoin (13-cis-retinoic acid; ISOT) will be administered by mouth over six courses as follows: If weight \> 12 kg: 80 mg/m\^2/dose twice daily (total daily dose is 160 mg/m\^2/day, divided twice daily). If weight ≤ 12 kg: 2.67 mg/kg/dose twice daily (total daily dose is 5.33 mg/kg/day, divided twice daily).
Eligibility Criteria
You may qualify if:
- Diagnosis of high-risk neuroblastoma
- 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
You may not qualify if:
- Prior anti-GD2 antibody therapy
- Prior vaccine therapy for neuroblastoma
- Concurrent anti-cancer or immunosuppressive therapy
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (13)
Children's Hospital of Los Angeles
Los Angeles, California, 90027, United States
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322, United States
The University of Chicago
Chicago, Illinois, 60637, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
University of Michigan C.S. Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404, United States
Children's Mercy Hospital (Kansas)
Kansas City, Missouri, 64108, United States
Washington University School of Medicine
St Louis, Missouri, 63310, United States
Columbia University Medical Center
New York, New York, 10032, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Cook Children's Medical Center
Fort Worth, Texas, 76104, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Allison Lim
- Organization
- United Therapeutics Corporation
Study Officials
- STUDY CHAIR
Araz Marachelian, MD
Children's Hospital Los Angeles
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 30, 2012
First Posted
May 4, 2012
Study Start
August 1, 2012
Primary Completion
June 1, 2014
Study Completion
June 1, 2014
Last Updated
September 23, 2015
Results First Posted
September 23, 2015
Record last verified: 2015-08