Biological Therapy, Sargramostim, and Isotretinoin in Treating Patients With Relapsed or Refractory Neuroblastoma
Feasibility/Phase II Study of hu14.18-IL2 Immunocytokine + GM-CSF and Isotretinoin in Patients With Relapsed or Refractory Neuroblastoma
5 other identifiers
interventional
52
2 countries
76
Brief Summary
This phase II trial is studying how well hu14.18-interleukin-2 (IL2) fusion protein works when given together with sargramostim and isotretinoin in treating patients with relapsed or refractory neuroblastoma. Biological therapy, such as hu14.18-IL2 fusion protein, and sargramostim work in different ways to stimulate the immune system and stop tumor cells from growing. Drugs used in chemotherapy, such as isotretinoin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving hu14.18-IL2 fusion protein together with sargramostim and isotretinoin may kill more tumor cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Sep 2011
Longer than P75 for phase_2
76 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
First Submitted
Initial submission to the registry
April 12, 2011
CompletedFirst Posted
Study publicly available on registry
April 13, 2011
CompletedStudy Start
First participant enrolled
September 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2013
CompletedResults Posted
Study results publicly available
February 20, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
September 30, 2019
CompletedOctober 21, 2019
October 1, 2019
2.3 years
April 12, 2011
February 4, 2015
October 4, 2019
Conditions
Outcome Measures
Primary Outcomes (1)
Number of Patients With Unacceptable Dose Limiting Toxicities (DLTs)
Test for tolerability and monitor for the occurrence of too many unacceptable DLTs using a two-stage stopping rule: (Stage 1) Accrue 10 patients. If more than 1 experience at least one unacceptable DLT during the first treatment cycle, the regimen will be considered to have unacceptable toxicity, and accrual will be temporarily closed, to review all relevant data and consider modifying the regimen to improve safety. If 1 or no patients have an unacceptable DLT in the first treatment cycle, then continue. (Stage 2) Accrue 20 more patients. If 7 or more experience at least one unacceptable DLT in the first treatment cycle, temporarily close the study for possible dosing-safety modifications. If 6 or fewer have an unacceptable DLT in the first treatment cycle, it is reasonable to assume that the combination therapy is safe.
Up to 10 courses
Secondary Outcomes (1)
Overall Response Evaluated in This Study Using the New International Criteria Proposed by the Revised Response Evaluation Criteria in Solid Tumors (RECIST)
Every two cycles (each cycle lasts 28 days)
Study Arms (2)
Disease measured by standard radiographic criteria
EXPERIMENTALTreatment (hu14.18-Interleukin 2(IL2) fusion protein and isotretinoin). Patients receive sargramostim (SC \[preferred\]) or IV over 2 hours on days 1-2 and 8-14, hu14.18-IL2 fusion protein IV over 4 hours on days 4-6, and isotretinoin PO twice daily on days 11-24. Treatment repeats every 28 days for 4-10 courses in the absence of disease progression or unacceptable toxicity. Patients in stratum-1 who achieve stable disease (SD) after course 4 are removed from protocol therapy. Patients in stratum-2 who achieve SD after course 4 receive 2 additional courses of study treatment. Patients may undergo blood and bone marrow sample collection periodically for correlative studies.
Disease evaluable only by I-MIBG or BM histology
EXPERIMENTALTreatment (hu14.18-Interleukin 2(IL2) fusion protein and isotretinoin). Patients receive sargramostim (SC \[preferred\]) or IV over 2 hours on days 1-2 and 8-14, hu14.18-IL2 fusion protein IV over 4 hours on days 4-6, and isotretinoin PO twice daily on days 11-24. Treatment repeats every 28 days for 4-10 courses in the absence of disease progression or unacceptable toxicity. Patients in stratum-1 who achieve stable disease (SD) after course 4 are removed from protocol therapy. Patients in stratum-2 who achieve SD after course 4 receive 2 additional courses of study treatment. Patients may undergo blood and bone marrow sample collection periodically for correlative studies.
Interventions
Given IV
Given PO
Given SC
Correlative studies
Eligibility Criteria
You may qualify if:
- The target tumor is limited to neuroblastoma; patients must have had histologic verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines at the time of initial diagnosis
- Patients must have resistant/refractory or recurrent neuroblastoma
- Tumor imaging and bone marrow evaluation for histologic analysis of marrow tumor cell quantity must be obtained within 3 weeks (21 days) prior to enrollment onto study and patients must have one of the following:
- Measurable tumor on magnetic resonance imaging (MRI), computed tomography (CT) scan, or x-ray defined as minimum of 20 mm in at least one dimension; measurable is defined as minimum of 20 mm in at least one dimension; for patients who are in first response (i.e., those patients with persistent sites of tumor after frontline therapy, but who have never relapsed), a biopsy of a lesion or bone marrow must demonstrate viable neuroblastoma following completion of therapy; if the lesion was irradiated, the biopsy must be done at least 4 weeks after radiation is completed
- Meta iodo benzyl guanidine I 123 (MIBG) scan with positive uptake at minimum of one site; for patients in first response, a biopsy of site must demonstrate viable tumor; if lesion was radiated, biopsy must be done at least 4 weeks after radiation completed
- Bone marrow with tumor cells seen on routine morphology (not by neuron specific enolase (NSE) staining only) of bilateral aspirate and/or biopsy on one bone marrow sample
- Patients must have a performance status of 0, 1 or 2; use Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50 for patients =\< 16 years of age
- Patients must have a life expectancy of ≥ 8 weeks
- Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
- Myelosuppressive chemotherapy: Must not have received within 3 weeks of entry onto this study (4 weeks if prior nitrosourea).
- Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a non-myelosuppressive biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; for information on half-lives of these agents, refer to the table provided in the following link: https://members.childrensoncologygroup.org/\_files/disc/dvl/Half-lifetableforeligibility.pdf
- External beam radiation therapy (XRT): \>= 2 wks for local palliative XRT (small port); \>= 6 months must have elapsed if prior craniospinal XRT or if \>= 50% radiation of pelvis; \>= 6 weeks must have elapsed if other substantial bone marrow (BM) radiation
- Autologous stem cell transplant (ASCT): Patients are eligible \> 56 days after autologous stem cell infusion following myeloablative therapy; patients receiving an autologous stem cell infusion to support non-myeloablative therapy (including 131I-MIBG given as a single agent) are eligible at any time as long as they meet the hematologic and other organ function criteria for eligibility; patients who have received an allogenic stem cell transplant are excluded
- radioactive iodine (131 I) MIBG therapy: Patients are eligible \> 6 weeks after therapeutic 131I-MIBG
- Study specific limitations on prior therapy: Subjects who have previously received in vivo anti-GD2 monoclonal antibodies for biologic therapy or for tumor imaging, are eligible unless they have had progressive disease or a severe allergic reaction while receiving prior anti-disialoganglioside (GD2) therapy; subjects who have received autologous marrow infusions or autologous stem cell infusions using monoclonal antibody linked to beads to purge specimens, but no other form of anti-GD2 monoclonal antibody, are eligible
- +24 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 (as isotretinoin is known to be teratogenic)
- Female patients who are lactating must agree to stop breast-feeding
- Patients with symptoms of congestive heart failure or uncontrolled cardiac rhythm disturbance are not eligible
- Patients with symptomatic pleural effusions or ascites (requiring constant or intermittent drainage) because IL2 is associated with capillary leak are not eligible
- Patients who have had major surgery (i.e., laparotomy or thoracotomy) within the past 2 weeks are not eligible, due to the capillary leak associated with IL2
- Patients with organ allografts (including bone marrow or stem cell) due to the immune activating effects of IL2 are not eligible; patients receiving prior autologous bone marrow or stem cell re-infusions are eligible
- Patients with prior history of ventilator support related to lung injury (lung injury such as pneumonia, hemorrhagic pneumonitis, capillary leakage) are excluded
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Children's Oncology Grouplead
- National Cancer Institute (NCI)collaborator
Study Sites (76)
University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205, United States
Children's Oncology Group
Arcadia, California, 91006-3776, United States
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 Central California
Madera, California, 93636-8762, United States
Childrens Hospital of Orange County
Orange, California, 92868-3874, United States
Rady Children's Hospital - San Diego
San Diego, California, 92123, United States
University of California San Francisco Medical Center-Parnassus
San Francisco, California, 94143, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado, 80218, United States
Connecticut Children's Medical Center
Hartford, Connecticut, 06106, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Lee Memorial Health System
Fort Myers, Florida, 33901, United States
Nemours Children's Clinic - Jacksonville
Jacksonville, Florida, 32207-8426, United States
Miami Children's Hospital
Miami, Florida, 33155, United States
Florida Hospital
Orlando, Florida, 32803, United States
All Children's Hospital
St. Petersburg, Florida, 33701, United States
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322, United States
University of Hawaii
Honolulu, Hawaii, 96813, United States
University of Illinois
Chicago, Illinois, 60612, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637-1470, United States
Southern Illinois University
Springfield, Illinois, 62702, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
Raymond Blank Children's Hospital
Des Moines, Iowa, 50309, United States
University of Kentucky
Lexington, Kentucky, 40536, United States
Kosair Children's Hospital
Louisville, Kentucky, 40202, United States
Tulane University Health Sciences Center
New Orleans, Louisiana, 70112, United States
Children's Hospital-Main Campus
New Orleans, Louisiana, 70118, United States
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115, United States
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007, United States
Kalamazoo Center for Medical Studies
Kalamazoo, Michigan, 49008, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Morristown Memorial Hospital
Morristown, New Jersey, 07962, United States
Overlook Hospital
Summit, New Jersey, 07902, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Columbia University Medical Center
New York, New York, 10032, United States
State University of New York Upstate Medical University
Syracuse, New York, 13210, United States
New York Medical College
Valhalla, New York, 10595, United States
University of North Carolina
Chapel Hill, North Carolina, 27599, United States
Carolinas Medical Center
Charlotte, North Carolina, 28203, United States
Presbyterian Hospital
Charlotte, North Carolina, 28204, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
The Children's Medical Center of Dayton
Dayton, Ohio, 45404, United States
The Toledo Hospital/Toledo Children's Hospital
Toledo, Ohio, 43606, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Natalie W Bryant Cancer Center
Tulsa, Oklahoma, 74136, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Lehigh Valley Hospital - Muhlenberg
Bethlehem, Pennsylvania, 18017, United States
Penn State Hershey Children's Hospital
Hershey, Pennsylvania, 17033, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232, United States
Medical City Dallas Hospital
Dallas, Texas, 75230, United States
Cook Children's Medical Center
Fort Worth, Texas, 76104, United States
Primary Children's Medical Center
Salt Lake City, Utah, 84113, United States
Childrens Hospital-King's Daughters
Norfolk, Virginia, 23507, United States
Virginia Commonwealth University
Richmond, Virginia, 23298, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Saint Vincent Hospital
Green Bay, Wisconsin, 54301, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792, United States
Alberta Children's Hospital
Calgary, Alberta, T3B 6A8, Canada
British Columbia Children's Hospital
Vancouver, British Columbia, V6H 3V4, Canada
Hospital for Sick Children
Toronto, Ontario, M5G 1X8, Canada
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, H3H 1P3, Canada
Hospital Sainte-Justine
Montreal, Quebec, H3T 1C5, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Results Reporting Coordinator
- Organization
- Children's Oncology Group
Study Officials
- PRINCIPAL INVESTIGATOR
Suzanne Shusterman, MD
Children's Oncology Group
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 12, 2011
First Posted
April 13, 2011
Study Start
September 1, 2011
Primary Completion
December 31, 2013
Study Completion
September 30, 2019
Last Updated
October 21, 2019
Results First Posted
February 20, 2015
Record last verified: 2019-10