Neoplasms

All Conditions

Rare Diseases

Neuroblastoma

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

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Anti-Infective Agents

Analgesics

Tretinoin

Antibodies

Antibodies, Monoclonal

Molgramostim

Sargramostim

Aldesleukin

Immunoglobulins

Isotretinoin

Interleukin-2

Dinutuximab

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

Immunologic Factors

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

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

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

ch14.18 -NCI

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

ch14.18-UTC

GM-CSF will be administered SC at a dose of 250 mcg/m\^2/day for 14 days during Courses 1, 3, and 5.

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

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.

Aldesleukin (IL-2)

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).

Araz Marachelian, MD

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.

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

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

United Therapeutics

UTC ch14.18

NCI ch14.18

UTC ch14.18 for two courses followed by NCI ch14.18 for three courses

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.

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).

Sequence 1

NCI ch14.18 for two courses followed by UTC ch14.18 for three courses

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.

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).

Sequence 2

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Complete Response (CR)

Very Good Partial Response (VGPR)

Partial Response (PR)

At pre-ASCT evaluation, subjects must have met the International Neuroblastoma Response Criteria (INRC) for complete response (CR), very good partial response (VGPR) or partial response (PR) for primary site, soft tissue metastases, and bone metastases. Subjects who met those criteria were also required to meet the protocol specified criteria for bone marrow response.

Pre-ASCT Response

Twenty-eight subjects were enrolled in this study with all subjects receiving at least one dose of study therapy.

Allison Lim

Area Under the Plasma Concentration Curve (AUC)

Peak Plasma Concentration (Cmax)

Overall Study

Spots Global Cancer Trial Database for ch14.18 Pharmacokinetic Study in High-risk Neuroblastoma

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Study Description

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