Monoclonal Antibody Ch14.18, Sargramostim, Aldesleukin, and Isotretinoin After Autologous Stem Cell Transplant in Treating Patients With Neuroblastoma
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
5 other identifiers
interventional
105
1 country
32
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Dec 2009
Longer than P75 for phase_3
32 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 21, 2009
CompletedFirst Submitted
Initial submission to the registry
December 31, 2009
CompletedFirst Posted
Study publicly available on registry
January 1, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2013
CompletedResults Posted
Study results publicly available
February 19, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
June 30, 2021
CompletedAugust 17, 2021
June 1, 2021
4 years
December 31, 2009
February 3, 2015
July 30, 2021
Conditions
Outcome Measures
Primary Outcomes (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).
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.
Up to 6 courses of therapy
Secondary Outcomes (2)
Event-free Survival (EFS)
From enrollment until the first occurrence of relapse, progressive disease, secondary malignancy, or death, or until last contact if no event occurred, up to 3 years
Overall Survival (OS)
From enrollment until death, or until last contact with the patient, up to 3 years
Study Arms (1)
Treatment (Ch14.18, GM-CSF, IL-2, isotretinoin)
EXPERIMENTALPatients 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.
Interventions
Given IV
Correlative studies
Given IV
Given PO
Given IV or SC
Eligibility Criteria
You may qualify if:
- 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:
- month to \< 6 months: 0.4 mg/dL
- months to \< 1 year: 0.5 mg/dL
- to \< 2 years: 0.6 mg/dL
- to \< 6 years: 0.8 mg/dL
- +12 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (32)
Loma Linda University Medical Center
Loma Linda, California, 92354, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Children's Hospital of Orange County
Orange, California, 92868, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304, United States
Rady Children's Hospital - San Diego
San Diego, California, 92123, United States
UCSF Medical Center-Mount Zion
San Francisco, California, 94115, United States
UCSF Medical Center-Parnassus
San Francisco, California, 94143, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
Children's Hospital New Orleans
New Orleans, Louisiana, 70118, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
New York Medical College
Valhalla, New York, 10595, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
Cook Children's Medical Center
Fort Worth, Texas, 76104, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792, United States
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Results Reporting Coordinator
- Organization
- Children's Oncology Group
Study Officials
- PRINCIPAL INVESTIGATOR
Mehmet F Ozkaynak
Children's Oncology Group
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 31, 2009
First Posted
January 1, 2010
Study Start
December 21, 2009
Primary Completion
December 31, 2013
Study Completion
June 30, 2021
Last Updated
August 17, 2021
Results First Posted
February 19, 2015
Record last verified: 2021-06