A Phase I Trial Of The Humanized Anti-GD2 Antibody In Children And Adolescents With Neuroblastoma, Osteosarcoma, Ewing Sarcoma and Melanoma

SJGD2 is a Phase I dose finding study. The primary purpose of this phase I study is to
determine the maximum tolerated dose (MTD) and dose-limiting toxicity of the humanized
monoclonal anti-GD2 antibody, hu14.18K322A, in research participants with refractory or
relapsed neuroblastoma or melanoma (Parts A and B) or osteosarcoma or Ewing sarcoma (Part
C).

Initially, in Part A, one research participant will be treated at the lowest dose level of
hu14.18K322A antibody [2 mg/m^2 daily for 4 consecutive days every 28 days (1 course)], and
if no toxicity is observed then the next participant will be treated at the next dose level.
This is continued until the first instance of biological activity (in the form of grade 2
side effects) is observed and from that point on a traditional phase I study design will be
followed. A maximum of 4 courses may be given.

Part B: Hu14.18K322A antibody will be administered intravenously (IV) at a starting dose of
50 mg/m^2/dose weekly for 4 doses per course. One course is considered 28 days. A maximum of
8 courses may be given.

Part C: Hu14.18K322A antibody will be administered to 6 patients each with
refractory/recurrent osteosarcoma at a maximum tolerated dose (MTD) of 60 mg/m^2 daily for 4
consecutive days every 28 days (Part C1). A cohort of patients with refractory/recurrent
osteosarcoma or Ewing sarcoma will also be administered hu14.18K322A antibody at starting
dose of 40 mg/m^2/dose weekly for 4 doses per course (Part C2). Participants will continue
on treatment for a maximum of 8 courses.

Secondary objectives include:

1. Estimate the response rate, within the confines of a phase I study, to the humanized
anti-GD2 antibody, hu14.18K322A.

2. Evaluate the pharmacokinetics of hu14.18K322A.

3. Examine whether or not human anti-human antibodies (HAHA) develop in participants
receiving hu14.18K322A.

4. Assess the tolerability of the hu14.18K322A at the MTD of the daily x4 and the weekly
dosing in patients with refractory or recurrent osteosarcoma.

Inclusion Criteria:

- Diagnosis:

- Part A: Recurrent or refractory neuroblastoma or melanoma.

- Part B: Recurrent or refractory neuroblastoma or melanoma.

- Part C: Recurrent or refractory osteosarcoma and Ewing sarcoma.

- Age: ≤ 21 years of age at the time of enrollment (i.e. participants are eligible
until they reach their 22nd birthday).

- Does not have a clinically significant neurologic deficit or objective peripheral
neuropathy (greater than or equal to grade 2). Peripheral (sensory or motor)
neuropathy related to limb sparing procedure or amputation is allowed.

- Life expectancy: at least 8 weeks.

- Organ Function: Must have adequate organ and marrow function

- Performance status: Karnofsky ≥ 50 for > 10 years of age; Lansky ≥ 50 for children <
10 years of age.

- Prior Therapy: Patient must have fully recovered from the acute toxic effects of all
prior therapy prior to enrolling on study.

- Myelosuppressive Chemotherapy: Must not have received myelosuppressive therapy
within 2 weeks prior to study entry (4 weeks if nitrosurea).

- Biologic (anti-neoplastic agent): At least 7 days since the completion of
therapy with biologic agent, including retinoic acid. Participants receiving
IVIG are eligible; however, participant must not receive IVIG during the 4 days
of antibody infusion.

- Radiation therapy: At least 2 weeks since prior local radiation therapy at the
time of study entry.

- Growth factors: Must not have received hematopoietic growth factors (G-CSF,
GM-CSF) for at least 1 week prior to study entry.

- Investigational agent: Must not have received investigational agent within 14
days of study entry.

- Immune therapy: Must not have received immunosuppressive (including
glucocorticoids), immunostimulatory or any immunomodulatory treatment within 2
weeks of study entry. Steroid containing inhalers, steroid replacement for
adrenal insufficiency and steroid premedication for prevention of transfusion or
imaging contrast agent-related allergic reaction will be permitted.

- Patients may have had prior CNS metastasis providing: CNS disease has been previously
treated and CNS disease has been clinically stable for 4 weeks prior to study entry
(assessment must be made by CT or MRI).

- Written informed consent following institutional and federal guidelines.

Exclusion Criteria:

- Prior monoclonal antibody: Participants having received in vivo monoclonal antibodies
for biologic therapy or for tumor imaging are eligible provided they did not
experience a severe allergic reaction with the antibody.

- Pregnancy or Breast Feeding: Study participants who are pregnant are not eligible for
this study. Pregnancy tests must be obtained in girls who are > 10 years of age or
post-menarchal within 7 days prior to study enrollment. Males or females of
reproductive potential may not participate unless they have agreed to use an
effective contraceptive method during participation in the trial. Breast feeding
should be discontinued if a mother wishes to participate in this study.

- Allergy: known hypersensitivity to other recombinant human antibodies.

- An uncontrolled infection.