N2001-02: I-MIBG With Intensive Chemotherapy and Autologous Stem Cell Rescue for High-Risk Neuroblastoma
Condition: Neuroblastoma
MeSH terms: Neuroblastoma
Intervention: Filgrastim; Carboplatin; Etoposide; Melphalan; Peripheral blood stem cell infusion; 131I-MIBG; Radiation therapy
Intervention description: Filgrastim 5 micrograms/kg/day S.C. or IV will be given daily beginning on Day 0. The first dose should begin four hours after the stem cell infusion is completed. Filgrastim will continue daily until the ANC >=1500/uL for three consecutive days.; The carboplatin will be administered as a continuous IV infusion Day - 7 through Day - 4, with dosing based upon pretreatment GFR levels. The carboplatin should be diluted to a concentration of 0.3 mg/ml in D5W 0.45NS and infused concomitantly with etoposide through the same central venous catheter using a "Y" connector; a controlled rate infusion pump is used for each arm of the "Y".; The etoposide shall be administered day -7 through day -4 via continuous intravenous infusion over 96 hours. For patients with a corrected GFR >= 100 ml/min/1.72 m^2, a dose of 300 mg/m^2/day (10 mg/kg/day if child is < 12 kg) shall be given. For patients with a corrected GFR 60-99 ml/min/1.72 m^2, the etoposide will be administered at a dose of 160 mg/m^2/day (5.3 mg/kg/day). The etoposide will be diluted in D5W 0.45%NS at a concentration of < 0.4 mg/ml. Etoposide should not be mixed with carboplatin, but administered using a Y-connector.; For patients in either the normal GFR strata (>=100 ml/min/1.73 m^2), or reduced GFR strata (60-99 ml/min/1.73m^2), melphalan shall be administered at a dose of 60 mg/m^2/day (2 mg/kg/day if child is < 12 kg) on day -7, -6, and -5 of study. The melphalan should be infused at a rate of less than 10 mg/minute, and should complete within 1 hour of reconstitution each day. The melphalan should be diluted in 0.9% NaCl at a concentration < 2 mg/ml. The total dosage of melphalan to be administered will be 180 mg/m^2.; Stem cells or marrow will be infused on day 0 of study therapy. Where the DMSO concentration in the stem cell product would exceed accepted level for infusion within a 24 hour period, stem cell products may be infused over two days to meet this standard. For purged PBSC: A minimum of 2.0 x 10^6 viable CD34+ cells/kg must be available. For unpurged PBSC, a minimum of 2.0 x 10^6 viable CD34+ cells/kg must be available. Having a back-up of 2.0 x 10^6 viable CD34+ cells/kg purged or unpurged PBSC is recommended but not required. For purged bone marrow, a minimum of 1.5 x10^8 mononuclear cells/kg must be available.; Therapeutic 131I MIBG will be synthesized by Draximage Canada.with specific activity between 15 and 25mCi/ml. Radiopurity will be initially determined by Draximage, prior to shipment to participating centers. Free radioiodide content must then be rechecked at the treating center prior to infusion using HPLC or Sep-Pac methodology.; Local irradiation is to be given to previously non-irradiated primary and metastatic sites of disease. Local irradiation should not start till the patient is medically stable, has an ANC > 1000/uL, platelets > 30,000 / uL, and is > 42 days post transplant. Recommended radiation guidelines consist of 2160 cGy total, given over 12 days using a single 180 cGy fraction/day. Any delay in local radiation that would extend treatment beyond day +84 should be discussed with the study chair. Local radiation will be administered at a participating NANT member site.
Intervention MeSH terms: Carboplatin; Etoposide; Melphalan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 1 Year
Maximum age: 29 Years
Healthy volunteers: No
Keywords: recurrent neuroblastoma

Summary:

      RATIONALE: Radioactive drugs, such as iodine I 131 metaiodobenzylguanidine, may carry
      radiation directly to tumor cells and not harm normal cells. Drugs used in chemotherapy, such
      as carboplatin, etoposide, and melphalan, work in different ways to stop the growth of tumor
      cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses
      high-energy x-rays to kill tumor cells. An autologous peripheral stem cell or bone marrow
      transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and
      radiation therapy. Giving iodine I 131 metaiodobenzylguanidine and combination chemotherapy
      with an autologous peripheral stem cell or bone marrow transplant may allow more chemotherapy
      to be given so that more tumor cells are killed. Giving radiation therapy after an autologous
      peripheral stem cell or bone marrow transplant may kill any remaining tumor cells.

      PURPOSE: This phase II trial is studying how well giving iodine I 131 metaiodobenzylguanidine
      together with combination chemotherapy and radiation therapy works in treating patients who
      are undergoing an autologous peripheral stem cell or bone marrow transplant for relapsed or
      refractory neuroblastoma.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosis of relapsed or refractory neuroblastoma

               -  Histologically confirmed and/or demonstration of tumor cells in bone marrow with
                  elevated urinary catecholamine metabolites

               -  High-risk neuroblastoma must meet one of the following:

                    -  Progressive disease prior to or after completion of induction therapy

                    -  Mixed response or no response after completion of 4 courses of induction
                       therapy

                    -  Partial response after 4 courses of induction therapy allowed provided no
                       prior participation in COG-A3973 or other phase III COG trials

          -  Measurable disease, defined as at least one metaiodobenzylguanidine (MIBG)-avid target
             lesion determined by diagnostic MIBG scan within 6 weeks of study entry (tumor sites
             that have received local irradiation within 3 months of study entry are not considered
             target lesions)

        PATIENT CHARACTERISTICS:

        Performance status

          -  Lansky 60-100% OR

          -  Karnofsky 60-100%

        Life expectancy

          -  At least 2 months

        Hematopoietic

          -  Hemoglobin ≥ 10 g/dL

          -  Absolute neutrophil count ≥ 750/mm^3

          -  Platelet count ≥ 50,000/mm^3 (if no marrow involvement by morphologic exam/no
             transfusion allowed) (> 20,000/mm^3 if metastatic tumor involvement of marrow by
             morphologic exam/transfusion allowed)

        Hepatic

          -  Bilirubin < 1.3 mg/dL

          -  SGOT and SGPT < 5 times normal

          -  Hepatitis B surface antigen negative

          -  Hepatitis C negative

        Renal

          -  Glomerular filtration rate or creatinine clearance ≥ 60 ml/min

          -  Creatinine ≤ 1.5 times normal for age as follows:

               -  0.8 mg/dL (for patients ≤ 5 years of age)

               -  1.0 mg/dL (for patients 6 to 10 years of age)

               -  1.2 mg/dL (for patients 11 to 15 years of age)

               -  1.5 mg/dL (for patients > 15 years of age)

        Cardiovascular

          -  Ejection fraction ≥ 55% by echocardiogram or radionuclide MUGA OR

          -  Fractional shortening ≥ 27% by echocardiogram

        Pulmonary

          -  Normal lung function defined as no dyspnea at rest and no oxygen requirement OR
             measured oxygen saturation > 93% on room air

        Other

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  No disease of any major organ system that would preclude study compliance

          -  No concurrent hemodialysis

          -  No active infection requiring IV antivirals, antibiotics, or antifungals (patients on
             antifungal therapy are eligible provided they are culture- and biopsy-negative in
             suspected residual radiographic lesions)

          -  Patient weight within limits to receive ≤ maximum total allowable dose of ^131I-MIBG

        PRIOR CONCURRENT THERAPY:

        Biologic therapy

          -  No prior myeloablative transplantation

               -  Prior submyeloablative transplantation allowed at discretion of principal
                  investigator

          -  More than 3 weeks since prior biologic therapy

        Chemotherapy

          -  More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for mitomycin C
             or nitrosoureas)

          -  No prior melphalan therapy with a total dose of > 100 mg/m^2

        Radiotherapy

          -  See Disease Characteristics

          -  At least 6 weeks since prior radiotherapy (6 months for craniospinal or whole lung
             radiotherapy)

          -  No prior total body irradiation

          -  No prior iodine I 131 MIBG (^131I-MIBG)

          -  No prior total abdominal or whole liver radiotherapy

          -  No prior local radiotherapy, including any of the following:

               -  1200 cGy to more than 33% of both kidneys (patient must have at least one kidney
                  that has not exceeded the dose/volume of radiation listed)

               -  1800 cGy to more than 30% of liver and/or 900 cGy to more than 50% of liver

        Other

          -  Recovered from all prior therapy

          -  No medications with a potential interference of ^131I-MIBG uptake 1 week before and 2
             weeks after completion of ^131I-MIBG