Safety Study of Dinutuximab Combined With Immunotherapy to Treat Neuroblastoma
- Conditions
- Effects of ImmunotherapyNeuroblastomaNeoplasm, Residual
- Interventions
- Drug: Dinutuximab. Immunotherapy
- Registration Number
- NCT02169609
- Lead Sponsor
- Fundació Sant Joan de Déu
- 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.
- Detailed Description
Assess toxicity and safety of subcutaneous GM-CSF and iv IL-2 in enhancing Dinutuximab-mediated ablation of Bone Marrow (BM) disease in patients with high-risk neuroblastoma who have achieved a Complete Response or Very Good Partial Response of the macroscopic disease in the investigators institution.
Assess response of minimal residual disease (MRD) of the anti-GD2 monoclonal antibody Dinutuximab combined with granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-2 in patients with high-risk neuroblastoma (NB). More precisely, to apply real-time quantitative RT-PCR to test the hypothesis that minimal residual disease content of BM after the first treatments with dinutuximab/GM-CSF has significant prognostic impact on relapse-free survival.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 24
-
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
3 - Patients must have a Lansky or Karnofsky Performance Scale score of > 50% and patients must have a life expectancy of > 2 months.
-
4- 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.
5 - 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.
6 - 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.
7 - Signed informed consent indicating awareness of the investigational nature of this program.
-
- 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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Dinutuximab. Immunotherapy Dinutuximab. Immunotherapy 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
- Primary Outcome Measures
Name Time Method Number of Participants with Serious and Non-Serious Adverse Events 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. 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.
- Secondary Outcome Measures
Name Time Method Relapse-free survival Anticipated, 2 years from study treatment initiation. From IC signature, every 3 months, up to 2 years (anticipated). Rate of BM response for patients with detectable minimal residual disease in the BM after the first treatments with Dinutuximab/GM-CSF and relation with relapse-free survival.
Trial Locations
- Locations (1)
Hospital Sant Joan de Deu
🇪🇸Barcelona, Spain