3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid for Primary Refractory Neuroblastoma in Bone Marrow
Condition: Neuroblastoma
MeSH terms: Neuroblastoma
Intervention: 3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic
Intervention description: This phase II, open-label, single arm trial assesses the anti-NB activity of high-dose 3F8 (80 mg/m2/day), which is used in cycles 1-2, with return to standard 3F8 dosage (20 mg/m2/day) in subsequent cycles.Clinical results will be compared to those in the predecessor trials which used only the standard 3F8 dosage. Starting with A(6), patients no longer receive high-dose 3F8 but receive only standard dose 3F8 (20mg/m2/day) for all cycles The patients have primary refractory BM disease. Protocol treatment is through 24 months.
Real-time quantitative RT-PCR63-65 will be used to assess MRD in BM. 13-cis-retinoic acid is started no later than after cycle 4 (i.e., after response is scored), but sooner if CR is achieved after cycles 1, 2, or 3, or if early HAMA develops.
Intervention MeSH terms: Immunomodulating Agents
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Minimum age: 18 Months
Healthy volunteers: No
Keywords: GM-CSF; MAB 3F8; RETINOIC ACID (CIS-9 & 13); 09-161

Summary:

      The purpose of this study is to see find out what effects, good and/or bad, the combination
      of 3F8 and GM-CSF has on the patient and the cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of NB as defined by a) histopathology (confirmed by the MSKCC Department of
             Pathology), or b) BM metastases or MIBG-avid lesion(s) plus high urine catecholamine
             levels.

          -  High-risk NB as defined by risk-related treatment guidelines1 and the International NB
             Staging System,89 i.e., stage 4 with (any age) or without (> or = to 18 months of age)
             MYCN amplification or MYCN-amplified stage 4S.

          -  Patients have primary refractory disease limited to BM, i.e., high-risk NB (defined
             above) resistant to standard therapy, as evidenced by incomplete response in BM, but
             no measurable MIBG-avid soft tissue tumor assessable for response and no progressive
             disease.

          -  Signed informed consent indicating awareness of the investigational nature of this
             program.

        Exclusion Criteria:

          -  Creatinine > 3.0 mg/dL

          -  ALT, AST and Alkaline Phosphatase > 5.0 times the upper limit of normal

          -  Bilirubin > 3.0 mg/dL

          -  Patients with grade 3 or higher toxicities (using the CTCAE v 4.0) related to cardiac,
             neurological, pulmonary or gastrointestinal function as determined by physical exam.
             Patients must have normal blood pressure for age.

          -  Progressive disease

          -  History of allergy to mouse proteins.

          -  Active life-threatening infection.

          -  Human anti-mouse antibody (HAMA) titer >1000 Elisa units/ml.

          -  Inability to comply with protocol requirements.