ch14.18 Pharmacokinetic Study in High-risk Neuroblastoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
United Therapeutics
ClinicalTrials.gov Identifier:
NCT01592045
First received: April 30, 2012
Last updated: April 23, 2014
Last verified: March 2014
  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

Resource links provided by NLM:


Further study details as provided by United Therapeutics:

Primary Outcome Measures:
  • 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



Secondary Outcome Measures:
  • Adverse Events [ Time Frame: Six months ] [ Designated as safety issue: Yes ]
    Adverse events measured throughout study.


Enrollment: 28
Study Start Date: August 2012
Study Completion Date: February 2014
Primary Completion Date: February 2014 (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
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01592045

Locations
United States, California
Children's Hospital of Los Angeles
Los Angeles, California, United States, 90027
United States, Georgia
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, United States, 30322
United States, Illinois
The University of Chicago
Chicago, Illinois, United States, 60637
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Michigan
University of Michigan C.S. Mott Children's Hospital
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, United States, 55404
United States, Missouri
Children's Mercy Hospital (Kansas)
Kansas, Missouri, United States, 64108
Washington University School of Medicine
St. Louis, Missouri, United States, 63310
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Cook Children's Medical Center
Fort Worth, Texas, United States, 76104
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
Sponsors and Collaborators
United Therapeutics
Investigators
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, 2014
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 August 28, 2014