Monoclonal Antibody Ch14.18, Sargramostim, Aldesleukin, and Isotretinoin After Autologous Stem Cell Transplant in Treating Patients With Neuroblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01041638
Recruitment Status : Completed
First Posted : January 1, 2010
Results First Posted : February 19, 2015
Last Update Posted : April 13, 2016
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase III trial is studying the side effects of giving monoclonal antibody Ch14.18 together with sargramostim, aldesleukin, and isotretinoin after autologous stem cell transplant in treating patients with neuroblastoma. Monoclonal antibodies, such as Ch14.18, may find tumor cells and help kill them. Colony-stimulating factors, such as sargramostim, may increase the number of immune cells found in bone marrow or peripheral blood. Aldesleukin may stimulate the white blood cells to kill tumor cells. Isotretinoin may help neuroblastoma cells become more like normal cells, and to grow and spread more slowly. Giving monoclonal antibody Ch14.18 with sargramostim, aldesleukin, and isotretinoin after autologous stem cell transplant may be an effective treatment for neuroblastoma.

Condition or disease Intervention/treatment Phase
Localized Resectable Neuroblastoma Localized Unresectable Neuroblastoma Regional Neuroblastoma Stage 4 Neuroblastoma Stage 4S Neuroblastoma Biological: Aldesleukin Other: Diagnostic Laboratory Biomarker Analysis Biological: Dinutuximab Drug: Isotretinoin Biological: Sargramostim Phase 3

Detailed Description:


I. To comprehensively define the safety profile of ch14.18 when administered with cytokines and isotretinoin in high-risk neuroblastoma patients after autologous stem cell transplant (ASCT).


I. To further describe and refine the event-free survival (EFS) and overall survival (OS) estimates and baseline characteristics for subjects receiving chl4.18 + cytokines + isotretinoin.

II. To further describe the safety and toxicity of chl4.18 + cytokines + isotretinoin with focus on: a) number of courses delivered per patient; b) number of dose reductions or stoppage (ch14.18 and/or interleukin [IL]-2 [aldesleukin]); and c) number of toxic deaths.

III. To further describe the immune reconstitution of patients following ASCT, based on laboratory data obtained just prior to, during, and after treatment with this regimen.

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


Patients receive sargramostim subcutaneously (SC) or intravenously (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 isotretinoin orally (PO) twice daily (BID) 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.

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 105 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : December 2009
Actual Primary Completion Date : April 2014

Arm Intervention/treatment
Experimental: Treatment (Ch14.18, GM-CSF, IL-2, isotretinoin)
Patients receive sargramostim SC 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 isotretinoin PO BID 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.
Biological: Aldesleukin
Given IV
Other Names:
  • 125-L-Serine-2-133-interleukin 2
  • Proleukin
  • r-serHuIL-2
  • Recombinant Human IL-2
  • Recombinant Human Interleukin-2
Other: Diagnostic Laboratory Biomarker Analysis
Correlative studies
Biological: Dinutuximab
Given IV
Other Names:
  • Ch 14.18UTC
  • Ch14.18
  • MOAB Ch14.18
  • monoclonal antibody Ch14.18
  • Unituxin
Drug: Isotretinoin
Given PO
Other Names:
  • 13-cis retinoic acid
  • 13-cis-Retinoate
  • 13-cis-Retinoic Acid
  • 13-cis-Vitamin A Acid
  • 13-cRA
  • Accure
  • Accutane
  • Amnesteem
  • cis-Retinoic Acid
  • Cistane
  • Claravis
  • Isotretinoinum
  • Isotrex
  • Isotrexin
  • Neovitamin A
  • Neovitamin A Acid
  • Oratane
  • Retinoicacid-13-cis
  • Ro 4-3780
  • Ro-4-3780
  • Roaccutan
  • Roaccutane
  • Roacutan
  • Sotret
Biological: Sargramostim
Given IV or SC
Other Names:
  • 23-L-Leucinecolony-Stimulating Factor 2
  • DRG-0012
  • Leukine
  • Prokine
  • rhu GM-CFS
  • Sagramostim
  • Sargramostatin

Primary Outcome Measures :
  1. Percentage of Patients Who Experienced a Significant (CTC Grade 3-5) Nonhematologic Toxicity of Interest (Pain, Hypotension, Allergic Reactions, Capillary Leak Syndrome, or Fever). [ Time Frame: Up to 5 years ]
    Designed to collect comprehensive safety/toxicity data, as well as additional efficacy data for the immunotherapy. To address the primary objective, descriptive analyses summarizing the number and type of AEs will be performed. The percentage of patients reporting each unacceptable (Grade 3 or higher) CTC toxicity code, tabulated by course, are reported.

Secondary Outcome Measures :
  1. Event-free Survival [ Time Frame: From enrollment until the first occurrence of relapse, progressive disease, secondary malignancy, or death, or until last contact if no event occurred, up to 5 years ]
    Estimated using Kaplan-Meier curves.

  2. Overall Survival [ Time Frame: From enrollment until death, or until last contact with the patient, up to 5 years ]
    Estimated using Kaplan-Meier curves.

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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • All patients must be diagnosed with neuroblastoma, and categorized as high-risk at the time of diagnosis
  • At pre-ASCT evaluation, patients must meet 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; patients who meet those criteria must also meet the protocol specified criteria for bone marrow response as outlined below: =< 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 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; (Note that, per INRC, this would have been defined as an "overall" response of progressive disease [PD])
  • Prior to enrollment on ANBL0931, a determination of residual disease must be performed (tumor imaging studies including metaiodobenzylguanidine [MIBG] scan, computed tomography [CT] or magnetic resonance imaging [MRI], bone marrow aspiration and biopsy); this disease assessment is required for eligibility, and should be done preferably within 2 weeks but must be done within a maximum of 4 weeks before enrollment

    • Patients with residual disease are eligible; biopsy is not required
    • Patients must not have progressive disease except for protocol specified bone marrow response
  • All patients must have completed therapy including intensive induction chemotherapy followed by ASCT and radiotherapy to be eligible; radiotherapy may be waived for patients who either had a small adrenal mass which was completely resected upfront, or who never had an identifiable primary tumor
  • No more than 9 months from the date of starting the first induction chemotherapy after diagnosis to the date of ASCT except for the rare occasions as noted below; for tandem ASCT patients, this will be the date of the FIRST stem cell infusion; Exception: for those who are 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
  • Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age; required patients must have a Lansky or Karnofsky performance scale score of >= 50%
  • Patients must have a life expectancy of >= 2 months (8 weeks)
  • Total absolute phagocyte count (APC = neutrophils + monocytes) is at least 1000/uL
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

    • 1 month to < 6 months: 0.4 mg/dL
    • 6 months to < 1 year: 0.5 mg/dL
    • 1 to < 2 years: 0.6 mg/dL
    • 2 to < 6 years: 0.8 mg/dL
    • 6 to < 10 years: 1 mg/dL
    • 10 to < 13 years: 1.2 mg/dL
    • 13 to < 16 years: 1.5 mg/dL (male), 1.4 mg/dL (female)
    • >= 16 years: 1.7 mg/dL (male), 1.4 mg/dL (female)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 5 x upper limit of normal (ULN) for age
  • SOS (sinusoidal obstruction syndrome, formerly known as veno-occlusive disease [VOD]), if present, should be stable or improving
  • Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 55% by radionuclide angiography
  • No evidence of dyspnea at rest
  • If pulmonary function tests (PFTs) are performed, forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) > 60% by pulmonary function test
  • Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
  • Central nervous system (CNS) toxicity < grade 2

Exclusion Criteria:

  • Females of childbearing potential must have a negative pregnancy test
  • Patients of childbearing potential must agree to use an effective birth control method
  • Female patients who are lactating must agree to stop breast-feeding
  • Patients must not have received prior anti-GD2 antibody therapy
  • Patients must not have received prior vaccine therapy administered as treatment of neuroblastoma not routine infectious disease vaccinations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01041638

  Hide Study Locations
United States, California
Loma Linda University Medical Center
Loma Linda, California, United States, 92354
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
Children's Hospital of Orange County
Orange, California, United States, 92868
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, United States, 94304
Rady Children's Hospital - San Diego
San Diego, California, United States, 92123
UCSF Medical Center-Parnassus
San Francisco, California, United States, 94143
United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
United States, Georgia
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, United States, 30322
United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637
United States, Indiana
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202
Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
United States, Louisiana
Children's Hospital New Orleans
New Orleans, Louisiana, United States, 70118
United States, Massachusetts
Dana-Farber/Harvard Cancer Center
Boston, Massachusetts, United States, 02115
United States, Michigan
C S Mott Children's Hospital
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, United States, 55404
United States, Missouri
The Childrens Mercy Hospital
Kansas City, Missouri, United States, 64108
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, New York
Columbia University/Herbert Irving Cancer Center
New York, New York, United States, 10032
New York Medical College
Valhalla, New York, United States, 10595
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Texas
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, United States, 75390
Cook Children's Medical Center
Fort Worth, Texas, United States, 76104
Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Mehmet Ozkaynak Children's Oncology Group

Responsible Party: National Cancer Institute (NCI) Identifier: NCT01041638     History of Changes
Other Study ID Numbers: NCI-2011-01997
NCI-2011-01997 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
ANBL0931 ( Other Identifier: Childrens Oncology Group )
ANBL0931 ( Other Identifier: CTEP )
U10CA098543 ( U.S. NIH Grant/Contract )
First Posted: January 1, 2010    Key Record Dates
Results First Posted: February 19, 2015
Last Update Posted: April 13, 2016
Last Verified: March 2016

Additional relevant MeSH terms:
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Keratolytic Agents
Dermatologic Agents