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ch14.18 Pharmacokinetic Study in High-risk Neuroblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01592045
Recruitment Status : Completed
First Posted : May 4, 2012
Results First Posted : September 23, 2015
Last Update Posted : September 23, 2015
Sponsor:
Information provided by (Responsible Party):
United Therapeutics

Tracking Information
First Submitted Date  ICMJE April 30, 2012
First Posted Date  ICMJE May 4, 2012
Results First Submitted Date  ICMJE June 3, 2015
Results First Posted Date  ICMJE September 23, 2015
Last Update Posted Date September 23, 2015
Study Start Date  ICMJE August 2012
Actual Primary Completion Date June 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 20, 2015)
  • Area Under the Plasma Concentration Curve (AUC) [ 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 ]
    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) [ 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 ]
    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
Original Primary Outcome Measures  ICMJE
 (submitted: May 2, 2012)
Area under the plasma concentration curve (AUC) [ Time Frame: 6 months ]
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
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: May 2, 2012)
Number of Participants with Adverse Events as a Measure of Safety and Tolerability. [ Time Frame: Six months ]
Adverse events measured throughout study.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE ch14.18 Pharmacokinetic Study in High-risk Neuroblastoma
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neuroblastoma
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 2, 2012)
28
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 2014
Actual Primary Completion Date June 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 8 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01592045
Other Study ID Numbers  ICMJE DIV-NB-201
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party United Therapeutics
Original Responsible Party Same as current
Current Study Sponsor  ICMJE United Therapeutics
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Araz Marachelian, MD Children's Hospital Los Angeles
PRS Account United Therapeutics
Verification Date August 2015

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