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A Comprehensive Safety Trial of Chimeric Antibody 14.18 (Ch14.18) With GM-CSF, IL-2 and Isotretinoin in High-Risk Neuroblastoma Patients Following Myeloablative Therapy

Phase 3
Open (Enrolling)
Disseminated Neuroblastoma, Localized Resectable Neuroblastoma, Localized Unresectable Neuroblastoma, Regional Neuroblastoma, Stage 4S Neuroblastoma

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Trial Information

A Comprehensive Safety Trial of Chimeric Antibody 14.18 (Ch14.18) With GM-CSF, IL-2 and Isotretinoin in High-Risk Neuroblastoma Patients Following Myeloablative Therapy


I. To comprehensively define the safety profile of monoclonal antibody Ch14.18 when
administered with sargramostim, aldesleukin, and isotretinoin after autologous stem cell
transplantation (ASCT) in patients with high-risk neuroblastoma.


I. To further describe and refine the event-free survival and overall survival estimates in
patients treated with this regimen.

II. To further describe the baseline characteristics of patients treated with these regimen.

III. To further describe the safety and toxicity of this regimen, in terms of number of
courses delivered per patient, number of dose reductions or stoppage, and number of toxic
deaths, in these patients.

IV. To further describe the immune reconstitution following ASCT based on laboratory data
obtained just before, during, and after treatment with this regimen.

V. To obtain correlative laboratory data to evaluate and describe mechanisms related to
response, toxicity of immune activation, and allergic phenomena.

OUTLINE: This is a multicenter study.

Patients receive sargramostim subcutaneously or IV over 2 hours on days 0-13 of courses 1,
3, and 5; monoclonal antibody Ch14.18 IV over 10 hours on days 3-6 of courses 1, 3, and 5
and on days 7-10 of courses 2 and 4; and oral isotretinoin twice daily on days 11-24 of
course 1, on days 14-27 of courses 2, 4, and 6, and on days 10-23 of courses 3 and 5.
Patients also receive aldesleukin IV continuously on days 0-3 and on days 7-10 of courses 2
and 4. Treatment repeats every 24-32 days for 6 courses in the absence of disease
progression or unacceptable toxicity.

Patients may undergo blood and bone marrow sample collection periodically for correlative
laboratory studies.

After completion of study therapy, patients are followed up every 3 months for 1 year, every
6 months for 4 years, and then annually thereafter.

Inclusion Criteria:

- Diagnosis of neuroblastoma

- High risk at diagnosis

- Meets the International Neuroblastoma Response Criteria (INRC) for complete response,
very good partial response, or partial response for primary site, soft tissue
metastasis, and bone metastasis AND meets the protocol-specified criteria for bone
marrow response

- No more than 10% tumor (of total nucleated cellular content) seen on any
specimen from a bilateral bone marrow aspirate/biopsy

- Patients who have no tumor seen on a prior bone marrow aspirate/biopsy
specimen and then have ≤ 10% tumor seen on any of the bilateral marrow
aspirate/biopsy specimens done at pre-autologous stem cell transplantation
(ASCT) and/or pre-study enrollment evaluation are eligible

- Residual disease by MIBG scan, CT scan, MRI, bone marrow aspiration, or biopsy

- No progressive disease other than protocol-specified bone marrow response as
described above

- Must have completed therapy that included intensive induction chemotherapy followed
by ASCT and radiotherapy within the past 100 days

- Radiotherapy may be waived for patients who either had a small adrenal mass that
was completely resected up-front or who never had an identifiable primary tumor

- No more than 9 months between the date of starting the first induction
chemotherapy after diagnosis to the date of ASCT (for patients who have
undergone tandem ASCT, this is the date of the first stem cell infusion)

- For patients who were initially diagnosed as non-high risk neuroblastoma,
but later converted (and/or relapsed) to high-risk neuroblastoma, the 9
months restriction should start from the date of induction therapy for
high-risk neuroblastoma (not from the initial induction therapy for
non-high-risk disease) to the date of ASCT

- Lansky performance status (PS) 50-100% (for patients ≤ 16 years of age) OR Karnofsky
PS 50-100% (for patients > 16 years of age)

- Life expectancy ≥ 2 months

- Absolute phagocyte count ≥ 1,000/μL

- Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR maximum serum creatinine
based on age/gender as follows:

- 0.4 mg/dL (1 to 5 months of age)

- 0.5 mg/dL (6 to 11 months of age)

- 0.6 mg/dL (1 year of age)

- 0.8 mg/dL (2 to 5 years of age)

- 1.0 mg/dL (6 to 9 years of age)

- 1.2 mg/dL (10 to 12 years of age)

- 1.5 mg/dL (males) or 1.4 mg/dL (females) (13 to 15 years of age)

- 1.7 mg/dL (males) or 1.4 mg/dL (females) (≥ 16 years of age)

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- ALT < 5 times ULN

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Shortening fraction ≥ 27% by ECHO OR ejection fraction ≥ 55% by radionuclide

- FEV_1/FVC > 60% by pulmonary function test (if performed)

- No evidence of dyspnea at rest

- No CNS toxicity ≥ grade 2

- Seizure disorder allowed provided patient is on anticonvulsants and it is well

- Sinusoidal obstruction syndrome allowed provided it is stable or improving

- No other concurrent anticancer therapy

- No prior anti-GD2 antibody therapy

- No prior vaccine therapy for neuroblastoma

- No concurrent pentoxifylline or immunosuppressive drugs (e.g., cyclosporine or
corticosteroids [other than for the treatment of acute allergic reactions to
immunotherapy or treatment of increased intracranial pressure in patients with CNS

- No other concurrent cytokines or growth factors

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number and type of adverse events assessed by Common Terminology Criteria for Adverse Events (CTCAE)

Outcome Time Frame:

Up to 5 years

Safety Issue:


Principal Investigator

Mehmet Ozkaynak

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

December 2009

Completion Date:

Related Keywords:

  • Disseminated Neuroblastoma
  • Localized Resectable Neuroblastoma
  • Localized Unresectable Neuroblastoma
  • Regional Neuroblastoma
  • Stage 4S Neuroblastoma
  • Neuroblastoma



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Indiana University Medical CenterIndianapolis, Indiana  46202
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Cook Children's Medical CenterFort Worth, Texas  76104
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The Childrens Mercy HospitalKansas City, Missouri  64108
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