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

April 30, 2012
April 23, 2014
August 2012
February 2014   (final data collection date for primary outcome measure)
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

Same as current
Complete list of historical versions of study NCT01592045 on ClinicalTrials.gov Archive Site
Adverse Events [ Time Frame: Six months ] [ Designated as safety issue: Yes ]
Adverse events measured throughout study.
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.
Not Provided
Not Provided
 
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

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]).

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.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Neuroblastoma
  • 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 1
    UTC ch14.18 for two courses and NCI ch14.18 for three courses
    Interventions:
    • Biological: ch14.18 -NCI
    • Biological: ch14.18-UTC
    • Biological: Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)
    • Biological: Aldesleukin (IL-2)
    • Drug: Isotretinoin
  • Experimental: Sequence 2
    NCI ch14.18 for two courses and UTC ch14.18 for three courses
    Interventions:
    • Biological: ch14.18 -NCI
    • Biological: ch14.18-UTC
    • Biological: Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)
    • Biological: Aldesleukin (IL-2)
    • Drug: Isotretinoin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
28
February 2014
February 2014   (final data collection date for primary outcome measure)

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
Both
up to 8 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01592045
DIV-NB-201
Yes
United Therapeutics
United Therapeutics
Not Provided
Study Chair: Araz Marachelian, MD Children's Hospital Los Angeles
United Therapeutics
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP