Back to resultsch14.18 Pharmacokinetic Study in High-risk Neuroblastoma
Primary Purpose
Neuroblastoma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ch14.18 -NCI
ch14.18-UTC
Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)
Aldesleukin (IL-2)
Isotretinoin
Sponsored by
About this trial
This is an interventional treatment trial for Neuroblastoma
Eligibility Criteria
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:
- Prior anti-GD2 antibody therapy
- Prior vaccine therapy for neuroblastoma
- Concurrent anti-cancer or immunosuppressive therapy
Sites / Locations
- Children's Hospital of Los Angeles
- Children's Healthcare of Atlanta - Egleston
- The University of Chicago
- Dana-Farber Cancer Institute
- University of Michigan C.S. Mott Children's Hospital
- Children's Hospitals and Clinics of Minnesota - Minneapolis
- Children's Mercy Hospital (Kansas)
- Washington University School of Medicine
- Columbia University Medical Center
- Duke University Medical Center
- Children's Hospital of Philadelphia
- Cook Children's Medical Center
- Seattle Children's Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Sequence 1
Sequence 2
Arm Description
UTC ch14.18 for two courses and NCI ch14.18 for three courses
NCI ch14.18 for two courses and UTC ch14.18 for three courses
Outcomes
Primary Outcome Measures
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
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
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01592045
Brief Title
ch14.18 Pharmacokinetic Study in High-risk Neuroblastoma
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2015
Overall Recruitment Status
Completed
Study Start Date
August 2012 (undefined)
Primary Completion Date
June 2014 (Actual)
Study Completion Date
June 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
United Therapeutics
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroblastoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sequence 1
Arm Type
Experimental
Arm Description
UTC ch14.18 for two courses and NCI ch14.18 for three courses
Arm Title
Sequence 2
Arm Type
Experimental
Arm Description
NCI ch14.18 for two courses and UTC ch14.18 for three courses
Intervention Type
Biological
Intervention Name(s)
ch14.18 -NCI
Intervention Description
25 mg/m^2/day IV for four consecutive days
Intervention Type
Biological
Intervention Name(s)
ch14.18-UTC
Intervention Description
17.5 mg/m^2/day IV for four consecutive days
Intervention Type
Biological
Intervention Name(s)
Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)
Intervention Description
GM-CSF will be administered SC at a dose of 250 mcg/m^2/day for 14 days during Courses 1, 3, and 5.
Intervention Type
Biological
Intervention Name(s)
Aldesleukin (IL-2)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Isotretinoin
Other Intervention Name(s)
13-cis-retinoic acid
Intervention Description
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).
Primary Outcome Measure Information:
Title
Area Under the Plasma Concentration Curve (AUC)
Description
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
Time Frame
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
Title
Peak Plasma Concentration (Cmax)
Description
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
Time Frame
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
10. Eligibility
Sex
All
Maximum Age & Unit of Time
8 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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:
Prior anti-GD2 antibody therapy
Prior vaccine therapy for neuroblastoma
Concurrent anti-cancer or immunosuppressive therapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Araz Marachelian, MD
Organizational Affiliation
Children's Hospital Los Angeles
Official's Role
Study Chair
Facility Information:
Facility Name
Children's Hospital of Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Children's Healthcare of Atlanta - Egleston
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
The University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Michigan C.S. Mott Children's Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Children's Hospitals and Clinics of Minnesota - Minneapolis
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
Children's Mercy Hospital (Kansas)
City
Kansas
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Washington University School of Medicine
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63310
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Cook Children's Medical Center
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
12. IPD Sharing Statement
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ch14.18 Pharmacokinetic Study in High-risk Neuroblastoma
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