Testing the Addition of 131I-MIBG or Lorlatinib to Intensive Therapy in People With High-Risk Neuroblastoma (NBL)
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| ClinicalTrials.gov Identifier: NCT03126916 |
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Recruitment Status :
Recruiting
First Posted : April 25, 2017
Last Update Posted : May 23, 2023
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Sponsor:
Children's Oncology Group
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
- Study Details
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Brief Summary:
This phase III trial studies iobenguane I-131 or lorlatinib and standard therapy in treating younger patients with newly-diagnosed high-risk neuroblastoma or ganglioneuroblastoma. Radioactive drugs, such as iobenguane I-131, may carry radiation directly to tumor cells and not harm normal cells. Lorlatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving iobenguane I-131 or lorlatinib and standard therapy may work better compared to lorlatinib and standard therapy alone in treating younger patients with neuroblastoma or ganglioneuroblastoma.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Ganglioneuroblastoma Neuroblastoma | Procedure: Autologous Hematopoietic Stem Cell Transplantation Drug: Busulfan Drug: Carboplatin Drug: Cisplatin Drug: Cyclophosphamide Drug: Dexrazoxane Hydrochloride Biological: Dinutuximab Drug: Doxorubicin Hydrochloride Drug: Etoposide Phosphate Radiation: External Beam Radiation Therapy Radiation: Iobenguane I-131 Drug: Isotretinoin Drug: Lorlatinib Drug: Melphalan Hydrochloride Biological: Sargramostim Procedure: Therapeutic Conventional Surgery Drug: Thiotepa Drug: Topotecan Hydrochloride Drug: Vincristine Sulfate | Phase 3 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 724 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 3 Study of 131I-Metaiodobenzylguanidine (131I-MIBG) or ALK Inhibitor Therapy Added to Intensive Therapy for Children With Newly Diagnosed High-Risk Neuroblastoma (NBL) |
| Actual Study Start Date : | May 9, 2018 |
| Estimated Primary Completion Date : | September 30, 2026 |
| Estimated Study Completion Date : | September 30, 2026 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Neuroblastoma
MedlinePlus related topics:
Neuroblastoma
Drug Information available for:
Iobenguane I 131
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm A (chemotherapy, HSCT, EBRT)
See Arm A in detailed description.
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Procedure: Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous HSCT
Other Names:
Drug: Carboplatin Given IV
Other Names:
Drug: Cisplatin Given IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Dexrazoxane Hydrochloride Given IV
Other Names:
Biological: Dinutuximab Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Drug: Etoposide Phosphate Given IV
Other Name: Etopophos Radiation: External Beam Radiation Therapy Undergo EBRT
Other Names:
Drug: Isotretinoin Given PO
Other Names:
Biological: Sargramostim Given SC
Other Names:
Procedure: Therapeutic Conventional Surgery Undergo standard of care surgery Drug: Thiotepa Given IV
Other Names:
Drug: Topotecan Hydrochloride Given IV
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Experimental: Arm B (Iobenguane I-131, chemotherapy, HSCT, EBRT)
See Arm B in detailed description.
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Procedure: Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous HSCT
Other Names:
Drug: Carboplatin Given IV
Other Names:
Drug: Cisplatin Given IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Dexrazoxane Hydrochloride Given IV
Other Names:
Biological: Dinutuximab Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Drug: Etoposide Phosphate Given IV
Other Name: Etopophos Radiation: External Beam Radiation Therapy Undergo EBRT
Other Names:
Radiation: Iobenguane I-131 Given IV
Other Names:
Drug: Isotretinoin Given PO
Other Names:
Biological: Sargramostim Given SC
Other Names:
Procedure: Therapeutic Conventional Surgery Undergo standard of care surgery Drug: Thiotepa Given IV
Other Names:
Drug: Topotecan Hydrochloride Given IV
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Experimental: Arm C (Iobenguane I-131, chemotherapy, BuMel, HSCT, EBRT)
See Arm C in detailed description. Closed to accrual as of 12/17/20.
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Procedure: Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous HSCT
Other Names:
Drug: Busulfan Given IV
Other Names:
Drug: Cisplatin Given IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Dexrazoxane Hydrochloride Given IV
Other Names:
Biological: Dinutuximab Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Drug: Etoposide Phosphate Given IV
Other Name: Etopophos Radiation: External Beam Radiation Therapy Undergo EBRT
Other Names:
Radiation: Iobenguane I-131 Given IV
Other Names:
Drug: Isotretinoin Given PO
Other Names:
Drug: Melphalan Hydrochloride Given IV
Other Names:
Biological: Sargramostim Given SC
Other Names:
Procedure: Therapeutic Conventional Surgery Undergo standard of care surgery Drug: Thiotepa Given IV
Other Names:
Drug: Topotecan Hydrochloride Given IV
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Experimental: Arm D (chemotherapy, HSCT, EBRT)
See Arm D in detailed description.
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Procedure: Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous HSCT
Other Names:
Drug: Carboplatin Given IV
Other Names:
Drug: Cisplatin Given IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Dexrazoxane Hydrochloride Given IV
Other Names:
Biological: Dinutuximab Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Drug: Etoposide Phosphate Given IV
Other Name: Etopophos Radiation: External Beam Radiation Therapy Undergo EBRT
Other Names:
Drug: Isotretinoin Given PO
Other Names:
Biological: Sargramostim Given SC
Other Names:
Procedure: Therapeutic Conventional Surgery Undergo standard of care surgery Drug: Thiotepa Given IV
Other Names:
Drug: Topotecan Hydrochloride Given IV
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Experimental: Arm E (lorlatinib, chemotherapy, HSCT, EBRT)
See Arm E in detailed description.
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Procedure: Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous HSCT
Other Names:
Drug: Carboplatin Given IV
Other Names:
Drug: Cisplatin Given IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Dexrazoxane Hydrochloride Given IV
Other Names:
Biological: Dinutuximab Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Drug: Etoposide Phosphate Given IV
Other Name: Etopophos Radiation: External Beam Radiation Therapy Undergo EBRT
Other Names:
Drug: Isotretinoin Given PO
Other Names:
Drug: Lorlatinib Given PO
Other Names:
Biological: Sargramostim Given SC
Other Names:
Procedure: Therapeutic Conventional Surgery Undergo standard of care surgery Drug: Thiotepa Given IV
Other Names:
Drug: Topotecan Hydrochloride Given IV
Other Names:
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Primary Outcome Measures :
- Event free survival (EFS) (Arm A, B, D, and E) [ Time Frame: 3 years ]EFS time is calculated from date of randomization or assignment to first episode of disease relapse or progression, second malignancy, or death, or until last contact if no event has occurred.
Secondary Outcome Measures :
- Incidence of adverse events [ Time Frame: Up to 18 months for Arms A-D and 28 months for Arm E ]The proportion of patients with at least one Grade 3 or higher toxicity during protocol therapy, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0, will be reported.
- EFS (Arm C) [ Time Frame: 3 years ]EFS time is calculated from date of randomization to first episode of disease relapse or progression, second malignancy, or death, or until last contact if no event has occurred.
- Overall survival (OS) [ Time Frame: 3 years ]OS time is calculated from date of randomization or assignment until death, or until last contact if patient is alive.
- Response rate [ Time Frame: Up to 6 months ]The response rate will be calculated among all evaluable patients at end-Induction. Responders are defined as patients who achieve a >= partial response (PR) per the revised International Neuroblastoma Response Criteria (INRC).
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 365 Days to 30 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Patients must be enrolled on ANBL00B1 (NCT00904241) or APEC14B1 (NCT02402244) prior to enrollment on ANBL1531 (NCT03126916)
- Patient must be >= 365 days and =< 30 years of age at diagnosis
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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; the following disease groups are eligible:
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Patients with International Neuroblastoma Risk Group (INRG) stage M disease are eligible if found to have 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 regardless of biologic features
- Patients with INRG stage MS disease with MYCN amplification
- Patients with INRG stage L2 disease with MYCN amplification
- Patients > 547 days of age initially diagnosed with INRG stage L1, L2 or MS disease who progressed to stage M without prior chemotherapy may enroll within 4 weeks of progression to stage M
- Patients >= 365 days of age initially diagnosed with MYCN amplified INRG stage L1 disease who progress to stage M without systemic therapy may enroll within 4 weeks of progression to stage M
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- Patients initially recognized to have high-risk disease must have had no prior systemic therapy (other than topotecan/cyclophosphamide initiated on an emergent basis and within allowed timing); patients observed or 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 the criteria will also be eligible; patients who receive localized emergency radiation to sites of life-threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis will be eligible
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Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/sex as follows:
- 1 to < 2 years: male = 0.6; female = 0.6
- 2 to < 6 years: male = 0.8; female = 0.8
- 6 to < 10 years: male = 1; female = 1
- 10 to < 13 years: male = 1.2; female = 1.2
- 13 to < 16 years: male = 1.5; female = 1.4
- >= 16 years: male = 1.7; female = 1.4
- Total bilirubin =< 1.5 x upper limit of normal (ULN) for age, and
- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 10 x ULN; for the purposes of this study, ULN for SGPT (ALT) is 45
- Shortening fraction of >= 27% by echocardiogram, or ejection fraction of > 50% by echocardiogram or radionuclide angiogram
- No known contraindication to peripheral blood stem cell (PBSC) collection; examples of contraindications might be a weight or size less than the collecting institution finds feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure
Exclusion Criteria:
- Patients with INRG stage L2 tumors without amplification of MYCN regardless of tumor histology (may meet criteria for high risk classification but are not eligible for this trial)
- Patients with bone marrow failure syndromes
- Patients for whom targeted radiopharmaceutical therapy would be contraindicated due to underlying medical disorders
- Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential
- 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
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 ClinicalTrials.gov identifier (NCT number): NCT03126916
Locations
Show 161 study locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Steven DuBois | Children's Oncology Group |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Children's Oncology Group |
| ClinicalTrials.gov Identifier: | NCT03126916 |
| Other Study ID Numbers: |
ANBL1531 NCI-2016-01734 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) ANBL1531 ( Other Identifier: Children's Oncology Group ) ANBL1531 ( Other Identifier: CTEP ) U10CA180886 ( U.S. NIH Grant/Contract ) |
| First Posted: | April 25, 2017 Key Record Dates |
| Last Update Posted: | May 23, 2023 |
| Last Verified: | April 2023 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Neuroblastoma Ganglioneuroblastoma Neuroectodermal Tumors, Primitive, Peripheral Neuroectodermal Tumors, Primitive Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Vitamin A Cyclophosphamide Melphalan Busulfan |
Thiotepa Cisplatin Carboplatin Doxorubicin Liposomal doxorubicin Etoposide Vincristine Topotecan Tretinoin Etoposide phosphate 3-Iodobenzylguanidine Dinutuximab Dexrazoxane Razoxane Isotretinoin |