Humanized 3F8 Monoclonal Antibody (Hu3F8) in Patients With High-Risk Neuroblastoma and GD2-Positive Tumors

Patients can be treated on 2 different schedules:

For patients following a 2 doses/cycle schedule (patients who were enrolled and started
treatment prior to Amendment A(8)), one cycle has 2 days of intravenous hu3F8 treatment,
given approximately 7 days apart.

For patients following a 3 doses/cycle schedule, one cycle has 3 days of intravenous hu3F8
treatment, given on days 1, 3 and 5. After Cycle 1, patients may receive treatment on a
modified schedule of 3 days of intravenous hu3F8 over 10 days, as needed. To limit
side-effects, patients receive analgesics and antihistamines as premedications. Cycles are 21
days and can be repeated up to a total of 12 cycles, see section 9.1 for details. Evaluations
before, during and after treatment are summarized in Tables 4A and B. In addition, to further
study the side effect of pain, patients will be asked to assess their pain on the days of
treatment with hu3F8 at 3 different time points: (a) prior to commencement of hu3F8, (b) at
least once during the acute pain episode when rescue pain medication doses are usually
required and (c) prior to discharge from the Pediatric Day Hospital.

Inclusion Criteria:

- Patients must have either (1) a diagnosis of NB as defined by international
criteria,56 i.e., histopathology (confirmed by the MSKCC Department of Pathology) or
BM metastases plus high urine catecholamine levels, or (2) a tumor that is
GD2-positive by immunostaining with m3F8.

°A non-NB tumor is defined as GD2-positive by immunostaining with m3F8. If fresh or
frozen tumor is not available for immunostaining, patients will be considered eligible
if published reports show that >50% of that tumor type is GD2-positive by
immunohistochemistry. (Note: Tissues must be fresh/frozen as fixed, paraffin-embedded
specimens are unsuitable for anti-GD2 immunostaining). Tumors known to be GD2-positive
by this criteria do not need immunostaining. These include: Melanoma (>50%),
Desmoplastic small round cell tumors (70%), Osteosarcoma (88%) and Soft tissue
sarcomas including liposarcoma, fibrosarcoma, malignant fibrous histiocytoma,
leiomyosarcoma, and spindle cell sarcoma (93%).

- Patients must have either (1) refractory or relapsed high-risk NB (including
MYCN-amplified stage 3/4/4S and MYCN-nonamplified stage 4 in patients greater than 18
months of age) resistant to standard therapy, or (2) refractory or relapsed
GD2-positive tumor.

- Patients must be older than 1 year of age.

- Prior treatment with murine 3F8 is allowed. Patients with prior m3F8 or ch14.18
treatment must have HAHA antibody titer less than the upper limit of normal [defined
as mean + 3*SD of normal volunteers].

- Negative serum pregnancy test in women of childbearing potential.

- Women of child-bearing potential must be willing to practice an effective method of
birth control while on treatment

- Signed informed consent indicating awareness of the investigational nature of this
program.

Exclusion Criteria:

- Existing major organ dysfunction > grade 2, with the exception of hearing loss and
myelosuppression defined as suppression of all types of WBCs, RBCs and platelets).
However, the following parameters must be met: white blood cell count ≥1000/ul,
absolute (neutrophil count ≥500/ul absolute lymphocyte count ≥500/ul and platelet
count ≥ to 25,000/ul

- Active life-threatening infection.

- Pregnant women or women who are breast-feeding.

- Inability to comply with protocol requirements.