ch14.18 Pharmacokinetic Study in High-risk Neuroblastoma

Neuroblastoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01592045
• Other study ID #: DIV-NB-201
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: April 30, 2012
• Last updated: August 20, 2015
• Start date: August 2012
• Est. completion date: June 2014

Study information

• Verified date: August 2015
• Source: United Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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]).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 8 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neuroblastoma

Intervention

Biological:
• ch14.18 -NCI
25 mg/m^2/day IV for four consecutive days
• ch14.18-UTC
17.5 mg/m^2/day IV for four consecutive days
• 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.
• 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).

Locations

Country	Name	City	State
United States	University of Michigan C.S. Mott Children's Hospital	Ann Arbor	Michigan
United States	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	The University of Chicago	Chicago	Illinois
United States	Duke University Medical Center	Durham	North Carolina
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Children's Mercy Hospital (Kansas)	Kansas	Missouri
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota
United States	Columbia University Medical Center	New York	New York
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Seattle Children's Hospital	Seattle	Washington
United States	Washington University School of Medicine	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
United Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	No
Primary	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	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	No