Safety Study of Dinutuximab Combined With Immunotherapy to Treat Neuroblastoma

• Status: Unknown status
• Trial end date: 2019-05-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Fundació Sant Joan de Déu
• Treatments: Antibodies, Monoclonal; Dinutuximab; Interleukin-2; Isotretinoin; Sargramostim; Tretinoin

Criteria

Inclusion Criteria:

1. 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.

2. 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.

Exclusion Criteria:

1. - Existing severe major organ dysfunction, i.e., renal., cardiac, hepatic, neurologic, pulmonary, or gastrointestinal toxicity ≥ grade 3.

2. - Progressive disease or MIBG-avid soft tissue/bone tumor.

3. - Active life-threatening infection.

4. - Inability to comply with protocol requirements.

5. - 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).