ch14.18 Pharmacokinetic Study in High-risk Neuroblastoma

NCT ID: NCT01592045

Last Updated: 2015-09-23

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

28 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-08-31

Study Completion Date

2014-06-30

Brief Summary

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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

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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.

Conditions

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Neuroblastoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Sequence 1

UTC ch14.18 for two courses and NCI ch14.18 for three courses

Group Type EXPERIMENTAL

ch14.18 -NCI

Intervention Type BIOLOGICAL

25 mg/m\^2/day IV for four consecutive days

ch14.18-UTC

Intervention Type BIOLOGICAL

17.5 mg/m\^2/day IV for four consecutive days

Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)

Intervention Type BIOLOGICAL

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)

Intervention Type BIOLOGICAL

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.

Isotretinoin

Intervention Type DRUG

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).

Sequence 2

NCI ch14.18 for two courses and UTC ch14.18 for three courses

Group Type EXPERIMENTAL

ch14.18 -NCI

Intervention Type BIOLOGICAL

25 mg/m\^2/day IV for four consecutive days

ch14.18-UTC

Intervention Type BIOLOGICAL

17.5 mg/m\^2/day IV for four consecutive days

Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)

Intervention Type BIOLOGICAL

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)

Intervention Type BIOLOGICAL

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.

Isotretinoin

Intervention Type DRUG

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).

Interventions

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ch14.18 -NCI

25 mg/m\^2/day IV for four consecutive days

Intervention Type BIOLOGICAL

ch14.18-UTC

17.5 mg/m\^2/day IV for four consecutive days

Intervention Type 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.

Intervention Type 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.

Intervention Type BIOLOGICAL

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).

Intervention Type DRUG

Other Intervention Names

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13-cis-retinoic acid

Eligibility Criteria

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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
Maximum Eligible Age

8 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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United Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Araz Marachelian, MD

Role: STUDY_CHAIR

Children's Hospital Los Angeles

Locations

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Children's Hospital of Los Angeles

Los Angeles, California, United States

Site Status

Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, United States

Site Status

The University of Chicago

Chicago, Illinois, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Michigan C.S. Mott Children's Hospital

Ann Arbor, Michigan, United States

Site Status

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, United States

Site Status

Children's Mercy Hospital (Kansas)

Kansas City, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Cook Children's Medical Center

Fort Worth, Texas, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

Countries

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United States

Other Identifiers

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DIV-NB-201

Identifier Type: -

Identifier Source: org_study_id

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