ch14.18 Pharmacokinetic Study in High-risk Neuroblastoma
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Purpose
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]).
| Condition | Intervention | Phase |
|---|---|---|
|
Neuroblastoma |
Biological: ch14.18 -NCI Biological: ch14.18-UTC Biological: Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Biological: Aldesleukin (IL-2) Drug: Isotretinoin |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment |
| 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 |
- Area under the plasma concentration curve (AUC) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
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
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability. [ Time Frame: Six months ] [ Designated as safety issue: Yes ]Adverse events measured throughout study.
| Estimated Enrollment: | 28 |
| Study Start Date: | August 2012 |
| Estimated Study Completion Date: | July 2013 |
| Estimated Primary Completion Date: | July 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Sequence 1
UTC ch14.18 for two courses and NCI ch14.18 for three courses
|
Biological: ch14.18 -NCI
25 mg/m^2/day IV for four consecutive days
Biological: ch14.18-UTC
17.5 mg/m^2/day IV for four consecutive days
Biological: Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)
GM-CSF will be administered SC at a dose of 250 mcg/m^2/day for 14 days during Courses 1, 3, and 5.
Biological: Aldesleukin (IL-2)
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.
Drug: Isotretinoin
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). Other Name: 13-cis-retinoic acid
|
|
Experimental: Sequence 2
NCI ch14.18 for two courses and UTC ch14.18 for three courses
|
Biological: ch14.18 -NCI
25 mg/m^2/day IV for four consecutive days
Biological: ch14.18-UTC
17.5 mg/m^2/day IV for four consecutive days
Biological: Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)
GM-CSF will be administered SC at a dose of 250 mcg/m^2/day for 14 days during Courses 1, 3, and 5.
Biological: Aldesleukin (IL-2)
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.
Drug: Isotretinoin
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). Other Name: 13-cis-retinoic acid
|
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.
Eligibility| Ages Eligible for Study: | up to 8 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| Contact: Allison Lim, PharmD | 919-425-8799 | alim@unither.com |
| United States, California | |
| Children's Hospital of Los Angeles | Recruiting |
| Los Angeles, California, United States, 90027 | |
| United States, Georgia | |
| Children's Healthcare of Atlanta - Egleston | Recruiting |
| Atlanta, Georgia, United States, 30322 | |
| United States, Illinois | |
| The University of Chicago | Recruiting |
| Chicago, Illinois, United States, 60637 | |
| United States, Massachusetts | |
| Dana-Farber Cancer Institute | Recruiting |
| Boston, Massachusetts, United States, 02215 | |
| United States, Michigan | |
| University of Michigan C.S. Mott Children's Hospital | Recruiting |
| Ann Arbor, Michigan, United States, 48109 | |
| United States, Minnesota | |
| Children's Hospitals and Clinics of Minnesota - Minneapolis | Recruiting |
| Minneapolis, Minnesota, United States, 55404 | |
| United States, Missouri | |
| Children's Mercy Hospital (Kansas) | Recruiting |
| Kansas, Missouri, United States, 64108 | |
| Washington University School of Medicine | Recruiting |
| St. Louis, Missouri, United States, 63310 | |
| United States, New York | |
| Columbia University Medical Center | Recruiting |
| New York, New York, United States, 10032 | |
| United States, North Carolina | |
| Duke University Medical Center | Recruiting |
| Durham, North Carolina, United States, 27710 | |
| United States, Pennsylvania | |
| Children's Hospital of Philadelphia | Recruiting |
| Philadelphia, Pennsylvania, United States, 19104 | |
| United States, Texas | |
| Cook Children's Medical Center | Recruiting |
| Fort Worth, Texas, United States, 76104 | |
| United States, Washington | |
| Seattle Children's Hospital | Recruiting |
| Seattle, Washington, United States, 98105 | |
| Study Chair: | Araz Marachelian, MD | Children's Hospital Los Angeles |
More Information
No publications provided
| Responsible Party: | United Therapeutics |
| ClinicalTrials.gov Identifier: | NCT01592045 History of Changes |
| Other Study ID Numbers: | DIV-NB-201 |
| Study First Received: | April 30, 2012 |
| Last Updated: | April 23, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Neuroblastoma Neuroectodermal Tumors, Primitive, Peripheral Neuroectodermal Tumors, Primitive Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Aldesleukin Interleukin-2 Tretinoin Isotretinoin Antineoplastic Agents |
Therapeutic Uses Pharmacologic Actions Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Central Nervous System Agents Dermatologic Agents Keratolytic Agents Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents |
ClinicalTrials.gov processed this record on May 23, 2013