Safety Study of Dinutuximab Combined With Immunotherapy to Treat Neuroblastoma

NCT02169609 | Completed Phase 2

• 1 other identifier: HSJD-HR-NB-Ch14.18
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate safety of the triple COG schema with the monoclonal antibody Dinutuximab + cytokines (GM-CSF and IL2) and isotretinoin (13-cis-retinoic acid, or RA) in patients with high-risk neuroblastoma.

Conditions

Neuroblastoma; Neoplasm, Residual; Effects of Immunotherapy

Keywords

Neuroblastoma; Immunotherapy; Dinutuximab

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Serious and Non-Serious Adverse Events

  Type, incidence, severity, timing, seriousness, and relatedness; of reported AEs, physical examinations, and laboratory tests. Toxicity will be graded and tabulated by the NCI-CTCAE v 4.0.

  Expected, 7 months from treatment initiation. From IC signature, every day during immunotherapy treatment (Cycles 1 to 5), day 1 of cycle 6. From patient consent signature up to 30 days after administration of the last dose of study drug.

Secondary Outcomes (1)

• Relapse-free survival

  Anticipated, 2 years from study treatment initiation. From IC signature, every 3 months, up to 2 years (anticipated).

Study Arms (1)

Dinutuximab. Immunotherapy

EXPERIMENTAL

Dinutuximab will be administered at 17.5 mg/m2/day for 4 days up to 5 courses. Each dose should be infused IV over approximately 10 hours. Immunotherapy (sargramostim + isotretinoin + interleukin2) Sargramostim will be administered at 250 micrograms/m2/d by subcutaneous (SC) injection daily from Day 0 through 13 (daily with the infusion of Dinutuximab and for 3 days before and 7 days afterward). Isotretinoin (13-cis-retinoic acid, or RA) (160mg/m2/day or 5.33mg/kg/day if \< 12kg) PO divided into 2 doses daily x 14 days. Interleukin-2 (IL-2) 3 MIU/m2/day will be given by continuous infusion for 4 days during the first week of each course 2 and 4 given on Days 0 - 3

Drug: Dinutuximab. Immunotherapy

Interventions

Dinutuximab. Immunotherapy DRUG

Patients will receive 5 courses of Dinutuximab + GM-CSF + IL2 at intervals of 28 days for all courses. In addition, all patients will receive isotretinoin (13-cis-retinoic acid, or RA) at 160 mg/m2/dose twice a day for 14 days every 28 days, for 6 courses. Patients come off study if progressive disease develops at any time after cycle 1 or life-threatening grade 4 toxicity occurs clearly attributable to Immunotherapy.

Also known as: Ch14.18, Sargramostim, GM-CSF, Isotretinoin, 13-cis-retinoic acid, or RA, Interleukin-2 (IL-2)

Dinutuximab. Immunotherapy

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of neuroblastoma as defined by international criteria by histopathology or bone marrow metastases. Patients age must be less than 18 years at the time of initial diagnosis.
• Neuroblastoma, as defined by risk-related treatment guidelines and the International Neuroblastoma Staging System, stage 4 with (any age) or without (\>18 months) MYCN-amplification, or MYCN-amplified neuroblastoma other than stage 1, or high-risk neuroblastoma defined based on the 3-gene molecular profile developed at our institution (Garcia I, et al. CCR 2012).
• Group 1 patients have neuroblastoma (as defined above) resistant to standard therapy, as evidenced by incomplete response in bone marrow, but no MIBG-avid soft tissue or bone tumor and no progressive disease.
• Group 2 patients have no evidence of measurable disease
• Patients must have a Lansky or Karnofsky Performance Scale score of \> 50% and patients must have a life expectancy of \> 2 months.
• Pre-enrollment tumor survey: Prior to enrollment a determination of residual disease must be Performed (Tumor imaging studies including CT or MRI, MIBG scan, bone marrow aspiration \& biopsy, and blood and bone marrow samples). This disease assessment is required for eligibility.
• Patients must have adequate organ functions at the time of registration:
• Hematological: Total absolute phagocyte count (APC = neutrophils + monocytes) is at least 1000/microL
• Renal: Adequate Renal Function Defined As: Creatinine clearance or radioisotope GFR \> 70 mL/min/1.73 m2 or serum creatinine based on age/gender.
• Hepatic- total bilirubin \< 1.5 x normal, and SGPT (ALT) \< 5 x normal. Veno-occlusive disease, if present, should be stable or improving.
• Cardiac- shortening fraction of \> 30% by echocardiogram, or if shortening fraction abnormal, ejection fraction of \> 55% by gated radionuclide study.
• Pulmonary- FEV1 and FVC \> 60% of predicted by pulmonary function test. For children who are unable to do PFTs, no evidence of dyspnea at rest, no exercise intolerance.
• Central nervous system- Patients with seizure disorder may be enrolled if on anticonvulsants and wellcontrolled. CNS toxicity \< Grade 2.
• 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.
• Signed informed consent indicating awareness of the investigational nature of this program.

You may not qualify if:

• \- Existing severe major organ dysfunction, i.e., renal., cardiac, hepatic, neurologic, pulmonary, or gastrointestinal toxicity ≥ grade 3.
• \- Progressive disease or MIBG-avid soft tissue/bone tumor.
• \- Active life-threatening infection.
• \- Inability to comply with protocol requirements.
• \- Patient is eligible for SIOP HR-NB-01 protocol (= newly diagnosed high-risk neuroblastoma patient in a center where the SIOP protocol is open for enrollment).

Sponsors & Collaborators

• Fundació Sant Joan de Déu: lead

Study Sites (1)

Hospital Sant Joan de Deu

Barcelona, Spain

Location

MeSH Terms

Conditions

Neuroblastoma; Neoplasm, Residual

Interventions

dinutuximab; sargramostim; Granulocyte-Macrophage Colony-Stimulating Factor; Isotretinoin; Interleukin-2

Condition Hierarchy (Ancestors)

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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Pigments, Biological; Interleukins; Lymphokines

Study Officials

• Jaume Mora, MD

  Hospital Sant Joan de Deu, Barcelona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2014
• First Posted: June 23, 2014
• Study Start: November 26, 2014
• Primary Completion: December 26, 2016
• Study Completion: December 31, 2018
• Last Updated: April 22, 2024

Record last verified: 2024-04

Locations

ES (1)