3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid for Consolidation of First Remission After Non-Myeloablative Therapy in Patients With High-Risk Neuroblastoma
Condition: Neuroblastoma
MeSH terms: Neuroblastoma
Intervention: 3F8 and 13-cis-retinoic acid
Intervention description: 3F8 is dosed at 80 mg/m2/day (cycles 1-2) or 20 mg/m2/day (cycles 3 and beyond) and infused iv over 30-90 minutes. 13-cis-retinoic acid is dosed at 160 mg/m2/day, divided into two doses, x14 days. If a dose is missed, it can be made up at the end of the cycle. It is not taken on same days as 3F8. *High-dose 3F8 will be administered only for patients enrolled on protocol from A(0) to A(7). Starting with A(8), patients receive standard dose (20mg/m2/day) during cycles 1 and 2.
Intervention MeSH terms: Tretinoin; Isotretinoin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 39.0
Sex: All
Minimum age: 18 Months
Healthy volunteers: No
Keywords: MAB 3F8; RETINOIC ACID (CIS-9 & 13); Bone Marrow; 09-159

Summary:

      The purpose of this study is to find out what effects, good and/or bad, the combination of
      3F8 and GM-CSF has on the patient and the cancer.

      Antibodies are made by the body to attack tumors and to fight infections. 3F8 is the name of
      one kind of antibody. It is made by mice, and it can attack neuroblastoma in people. 3F8 has
      been used safely in many patients, and it has killed cancer cells in some patients. One way
      it can kill cancer cells is by causing the patient's own white blood cells to attack the
      cancer. Granulocytes are one kind of white blood cell. GM-CSF increases the number of
      granulocytes in people, and it makes the granulocytes better able to kill the cancer cells.
    

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 (≥18 months of age) MYCN
             amplification, MYCN-amplified stage 2 or stage 3 (any age), or MYCN-amplified stage
             4S.

          -  The patients are in first CR/VGPR after conventional therapy. They have no measurable
             MIBG-avid soft tissue tumor assessable for response.

          -  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 v3.0) 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