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Treatment With Dinutuximab, Sargramostim (GM-CSF), and Isotretinoin in Combination With Irinotecan and Temozolomide After Intensive Therapy for People With High-Risk Neuroblastoma (NBL)
Study Purpose
This phase II trial studies if dinutuximab, GM-CSF, isotretinoin in combination with irinotecan, and temozolomide (chemo-immunotherapy) can be given safely to patients with high-risk neuroblastoma after Consolidation therapy (which usually consists of two autologous stem cell transplants and radiation) who have not experienced worsening or recurrence of their disease. Dinutuximab represents a kind of cancer therapy called immunotherapy. Unlike chemotherapy and radiation, dinutuximab targets the cancer cells without destroying nearby healthy cells. Sargramostim helps the body produce normal infection-fighting white blood cells. Isotretinoin helps the neuroblastoma cells become more mature. These 3 drugs (standard immunotherapy) are already given to patients with high-risk neuroblastoma after Consolidation because they have been proven to be beneficial in this setting. Chemotherapy drugs, such as irinotecan and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. They may also effect how well immunotherapy works on neuroblastoma cells. Giving chemo-immunotherapy after intensive therapy may work better in treating patients with high-risk neuroblastoma compared to standard immunotherapy.
Recruitment Criteria
Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms |
No |
Study Type
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies. |
Interventional |
Eligible Ages | N/A - 30 Years |
Gender | All |
Inclusion Criteria:
- - Patients must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular) (verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites at the time of diagnosis) and have been designated as having high-risk disease based on Children's Oncology Group (COG) risk classification.
- - Patients with International Neuroblastoma Risk Group (INRG) Stage M disease with any of the following features: - MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of additional biologic features; OR.
- - Age > 547 days at the time of diagnosis regardless of biologic features; OR.
- - Age 365-547 days at the time of diagnosis with tumors with unfavorable histology and/or deoxyribonucleic acid (DNA) index = 1.
- - Patients with INRG Stage MS disease with MYCN amplification.
- - Patients with INRG Stage L2 disease with either of the following features: - MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of additional biologic features; OR.
- - Age > 547 days at the time of diagnosis with MYCN non-amplified tumors with unfavorable histology.
- - Note: Patients observed or patients treated with a single cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (e.g., as per ANBL0531, ANBL1232 or similar) for what initially appeared to be non-high-risk disease but subsequently found to meet criteria will also be eligible.
- - Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2.
- - Prior therapy.
- - All patients must have completed high-risk Induction therapy with 4-6 cycles of chemotherapy.
- - After completion of Induction therapy, patients may have received no more than 4 cycles of bridging chemotherapy or chemo-immunotherapy prior to ASCT.
- - Patients cannot have previously progressed on immunotherapy with dinutuximab or other anti-GD2 monoclonal antibody.
- - All patients must have had undergone surgical resection of their primary tumor as part of frontline therapy.
- - All patients must have undergone tandem high-dose chemotherapy with ASCT as part of Consolidation.
- - Patients must enroll between day +56 and day +200 from the peripheral blood stem cell (PBSC) infusion following the last dose of high-dose chemotherapy during Consolidation.
- - All patients must have undergone external beam radiation therapy.
- - Patients must not have received long-acting myeloid growth factors (e.g., Neulasta) within 14 days of entry on this study.
- - Peripheral absolute neutrophil count (ANC) >= 750/uL.
- - Platelet count >= 50,000/uL (transfusion independent for >= 7 days) - 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: - Age: Maximum Serum Creatinine (mg/dL) - 6 months to < 1 year: 0.5 (male and female) - 1 to < 2 years: 0.6 (male and female) - 2 to < 6 years: 0.8 (male and female) - 6 to < 10 years: 1 (male and female) - 10 to < 13 years: 1.2 (male and female) - 13 to < 16 years: 1.5 (male), 1.4 (female) - >= 16 years: 1.7 (male), 1.4 (female) - Note: Patients with history of transplant associated-thrombotic microangiopathy (TA-TMA) must have a creatinine clearance or radioisotope GFR at baseline to assess renal function and must meet the above criteria.
- - Total bilirubin =< 1.5 x upper limit of normal (ULN) for age.
- - Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 5.0 x ULN for age (=< 225 U/L) - Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L.
- - Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by echocardiogram or radionuclide angiogram.
- - Absence of dyspnea at rest.
- - If pulmonary function tests (PFTs) are performed, forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) must be > 60% - No clinical evidence of active central nervous system (CNS) disease at the time of study enrollment.
- - Patients with seizure disorder may be enrolled if on non-enzyme-inducing anticonvulsants and well controlled.
- - CNS toxicity from prior therapy =< grade 2.
Exclusion Criteria:
- - Patients must not have had progressive disease (PD) per the revised International Neuroblastoma Risk Criteria (INRC) since the initial diagnosis of high-risk neuroblastoma.
- - Exception: Progressive disease within the first 2 cycles of Induction chemotherapy consisting of cyclophosphamide and topotecan is allowed.
- - Patients may not have received additional systemic cancer-directed therapy following completion of the last planned high-dose chemotherapy with ASCT prior to enrollment on this trial.
- - Patients may not have received iodine-131 (131I)-metaiodobenzylguanidine (MIBG) therapy at any time prior to enrollment on this trial.
- - Patients who received single (rather than tandem) high-dose chemotherapy with ASCT are excluded.
- - Patients cannot be receiving other ongoing anticancer therapy.
- - Patients who were enrolled onto ANBL1531 AND underwent arm assignment are not eligible.
- - Patients enrolled onto ANBL17P1 are not eligible.
- - Patients must have been off pharmacologic doses of systemic steroids for at least 7 days prior to enrollment.
- - Patients who require or are likely to require pharmacologic doses of systemic corticosteroids while receiving treatment on this study are ineligible.
- - Note: The use of conventional doses of inhaled steroids for the treatment of asthma is permitted, as is the use of physiologic doses of steroids for patients with known adrenal insufficiency.
- - Patients on any other immunosuppressive medications (e.g., cyclosporine, tacrolimus) are not eligible.
- - Patients must not have received enzyme-inducing anticonvulsants including phenytoin, phenobarbital, valproic acid, or carbamazepine for at least 7 days prior to study enrollment.
- - Note: Patients receiving non-enzyme inducing anticonvulsants such as gabapentin or levetiracetam are eligible.
- - Patients must not have received drugs that are strong inducers or inhibitors of CYP3A4 within 7 days prior to study enrollment.
- - Patients must not have been diagnosed with myelodysplastic syndrome or with any malignancy other than neuroblastoma.
- - Patients with symptoms of congestive heart failure are not eligible.
- - Patients with moderate or large pericardial effusions are not eligible.
- - Patients must not have >= grade 2 diarrhea.
- - Patients must not have uncontrolled infection.
- - Patients with a history of grade 4 allergic reactions to anti-GD2 antibodies or reactions that required discontinuation of the anti-GD2 therapy are not eligible.
- - Patients with a significant intercurrent illness (any ongoing serious medical problem unrelated to cancer or its treatment) that is not covered by the detailed exclusion criteria and that is expected to interfere with the action of study agents or to significantly increase the severity of the toxicities experienced from study treatment are not eligible.
- - Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs.
- - Lactating females who plan to breastfeed their infants.
- - Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation.
- - All patients and/or their parents or legal guardians must sign a written informed consent.
Trial Details
Trial ID:
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries. |
NCT04385277 |
Phase
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use. |
Phase 2 |
Lead Sponsor
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data. |
Children's Oncology Group |
Principal Investigator
The person who is responsible for the scientific and technical direction of the entire clinical study. |
Ami V Desai |
Principal Investigator Affiliation | Children's Oncology Group |
Agency Class
Category of organization(s) involved as sponsor (and collaborator) supporting the trial. |
Other, NIH |
Overall Status | Recruiting |
Countries | Australia, Canada, New Zealand, United States |
Conditions
The disease, disorder, syndrome, illness, or injury that is being studied. |
Ganglioneuroblastoma, Nodular, High Risk Neuroblastoma |
PRIMARY OBJECTIVE:
- I. To determine the feasibility of administering dinutuximab, GM-CSF, and isotretinoin in combination with irinotecan and temozolomide in the frontline Post-Consolidation setting in patients with high-risk neuroblastoma who have undergone Induction and Consolidation therapy with tandem high-dose chemotherapy with stem cell rescue (ASCT).
- I. To describe the toxicity profile of dinutuximab, GM-CSF, and isotretinoin in combination with irinotecan and temozolomide in the Post-Consolidation setting.
- II. To describe the event-free survival and overall survival of patients who receive dinutuximab in combination with irinotecan and temozolomide, GM-CSF, and isotretinoinin the Post-Consolidation setting.
- I. To describe the toxicity profiles associated with chemo-immunotherapy in the Post-Consolidation setting according to the type of prior therapy.
- II. To describe response to chemo-immunotherapy in the Post-Consolidation setting using the revised International Neuroblastoma Risk Classification (INRC) in patients with evaluable or measurable disease at study entry.
- III. To characterize immune and cytokine profiles in patients receiving Post-Consolidation chemo-immunotherapy.
- IV. To bank serial blood samples to investigate the relationship between factors related to the tumor, host, and immune environment and clinical outcomes in patients treated with chemo-immunotherapy.
Arms
Experimental: Treatment (temozolomide, irinotecan, dinutuximab)
Patients receive temozolomide PO or via enteral tube daily and irinotecan IV over 90 minutes daily on days 1-5, dinutuximab IV over 10-20 hours daily on days 2-5, sargramostim SC or IV over 2 hours daily on days 6-12, and isotretinoin PO BID on days 8-21. Treatment repeats every 28 days for 5 cycles (6 cycles for isotretinoin only) in the absence of disease progression or unacceptable toxicity.
Interventions
Biological: - Dinutuximab
Given IV
Drug: - Irinotecan
Given IV
Drug: - Isotretinoin
Given PO
Biological: - Sargramostim
Given SC or IV
Drug: - Temozolomide
Given PO or via enteral tube
Contact a Trial Team
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.
Status
Recruiting
Address
Banner Children's at Desert
Mesa, Arizona, 85202
Status
Recruiting
Address
Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591
Status
Recruiting
Address
Kaiser Permanente Downey Medical Center
Downey, California, 90242
Status
Recruiting
Address
Children's Hospital Los Angeles
Los Angeles, California, 90027
Status
Recruiting
Address
Kaiser Permanente-Oakland
Oakland, California, 94611
Status
Recruiting
Address
Children's Hospital of Orange County
Orange, California, 92868
Status
Recruiting
Address
UCSF Medical Center-Mission Bay
San Francisco, California, 94158
Status
Recruiting
Address
Children's Hospital Colorado
Aurora, Colorado, 80045
Status
Recruiting
Address
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado, 80218
Status
Recruiting
Address
Connecticut Children's Medical Center
Hartford, Connecticut, 06106
Status
Recruiting
Address
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803
Status
Recruiting
Address
Children's National Medical Center
Washington, District of Columbia, 20010
Status
Recruiting
Address
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908
Status
Recruiting
Address
University of Florida Health Science Center - Gainesville
Gainesville, Florida, 32610
Status
Recruiting
Address
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida, 33021
Status
Recruiting
Address
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207
Status
Not yet recruiting
Address
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Status
Recruiting
Address
Nemours Children's Hospital
Orlando, Florida, 32827
Status
Recruiting
Address
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322
Status
Recruiting
Address
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712
Status
Recruiting
Address
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611
Status
Recruiting
Address
University of Illinois
Chicago, Illinois, 60612
Status
Recruiting
Address
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Status
Recruiting
Address
Saint Jude Midwest Affiliate
Peoria, Illinois, 61637
Status
Recruiting
Address
Riley Hospital for Children
Indianapolis, Indiana, 46202
Status
Recruiting
Address
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
Status
Recruiting
Address
Norton Children's Hospital
Louisville, Kentucky, 40202
Status
Recruiting
Address
Ochsner Medical Center Jefferson
New Orleans, Louisiana, 70121
Status
Recruiting
Address
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889-5600
Status
Recruiting
Address
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Status
Recruiting
Address
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109
Status
Recruiting
Address
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404
Status
Recruiting
Address
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Status
Recruiting
Address
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
Status
Recruiting
Address
Washington University School of Medicine
Saint Louis, Missouri, 63110
Status
Recruiting
Address
Mercy Hospital Saint Louis
Saint Louis, Missouri, 63141
Status
Recruiting
Address
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, 68114
Status
Recruiting
Address
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Status
Withdrawn
Address
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Status
Recruiting
Address
Morristown Medical Center
Morristown, New Jersey, 07960
Status
Recruiting
Address
Albany Medical Center
Albany, New York, 12208
Status
Recruiting
Address
Montefiore Medical Center - Moses Campus
Bronx, New York, 10467
Status
Recruiting
Address
NYU Winthrop Hospital
Mineola, New York, 11501
Status
Recruiting
Address
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
Status
Recruiting
Address
State University of New York Upstate Medical University
Syracuse, New York, 13210
Status
Active, not recruiting
Address
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203
Status
Recruiting
Address
Sanford Broadway Medical Center
Fargo, North Dakota, 58122
Status
Recruiting
Address
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308
Status
Recruiting
Address
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Status
Recruiting
Address
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106
Status
Recruiting
Address
Nationwide Children's Hospital
Columbus, Ohio, 43205
Status
Recruiting
Address
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Status
Recruiting
Address
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Status
Recruiting
Address
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134
Status
Recruiting
Address
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Status
Recruiting
Address
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105
Status
Recruiting
Address
The Children's Hospital at TriStar Centennial
Nashville, Tennessee, 37203
Status
Recruiting
Address
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Status
Recruiting
Address
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723
Status
Recruiting
Address
Medical City Dallas Hospital
Dallas, Texas, 75230
Status
Recruiting
Address
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
Status
Recruiting
Address
El Paso Children's Hospital
El Paso, Texas, 79905
Status
Recruiting
Address
Cook Children's Medical Center
Fort Worth, Texas, 76104
Status
Recruiting
Address
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
Status
Recruiting
Address
Covenant Children's Hospital
Lubbock, Texas, 79410
Status
Recruiting
Address
UMC Cancer Center / UMC Health System
Lubbock, Texas, 79415
Status
Recruiting
Address
Children's Hospital of San Antonio
San Antonio, Texas, 78207
Status
Recruiting
Address
Methodist Children's Hospital of South Texas
San Antonio, Texas, 78229
Status
Recruiting
Address
Primary Children's Hospital
Salt Lake City, Utah, 84113
Status
Recruiting
Address
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507
Status
Recruiting
Address
Seattle Children's Hospital
Seattle, Washington, 98105
International Sites
Status
Recruiting
Address
The Children's Hospital at Westmead
Westmead, New South Wales, 2145
Status
Recruiting
Address
Queensland Children's Hospital
South Brisbane, Queensland, 4101
Status
Suspended
Address
Royal Children's Hospital
Parkville, Victoria, 3052
Status
Recruiting
Address
Perth Children's Hospital
Perth, Western Australia, 6009
Status
Recruiting
Address
IWK Health Centre
Halifax, Nova Scotia, B3K 6R8
Status
Recruiting
Address
Starship Children's Hospital
Grafton, Auckland, 1145
Status
Recruiting
Address
Christchurch Hospital
Christchurch, , 8011