This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a pilot study to assess the feasibility of a topotecan-containing novel Induction regimen in children with high risk neuroblastoma. This Induction regimen will utilize sequential administration of six cycles of multi-agent chemotherapy based upon the current A3973 Induction regimen (MSKCC N6), maintaining a similar dose intensity of known active anti-tumor agents and a similar duration of therapy (18 weeks). Based upon known synergistic anti-tumor activity, topotecan will be combined with cyclophosphamide and will replace the initial two cycles of vincristine/cyclophosphamide/doxorubicin administered in the current A3973 Induction regimen. Cyclophosphamide/topotecan will be delivered at doses above that achieved on pediatric Phase I and II trials. Dose escalation of topotecan is supported by pre-clinical murine neuroblastoma xenograft models that demonstrate a correlation between increased systemic exposure to topotecan and improved anti-tumor activity. Repetitive delivery of a topotecan and cyclophosphamide regimen of similar dose intensity has been feasible with expected increased hematologic toxicity. Observed hematologic toxicity of the dose intensive cyclophosphamide/topotecan combination was within the range of known toxicity during current high risk neuroblastoma Induction therapy utilized in A3973. Filgrastim (G-CSF) will be administered with each cycle of Induction chemotherapy to minimize hematologic toxicity. Protocol therapy will consist of Induction phase of chemotherapy, peripheral blood stem cell harvest and surgical resection of tumor; Continuation phase of myeloablative chemotherapy with stem cell rescue, and post-transplant external beam radiation therapy and Maintenance phase of biologic modifier therapy with cis-Retinoic acid. Topotecan pharmacokinetics will be obtained on Day 1 of cycle 1 and cycle 2 Induction with the goal of individualizing each patient's topotecan dosage to attain the desired topotecan target systemic exposure (e.g., single day topotecan lactone AUC 50 to 70 ng/ml*hr). Peripheral blood stem cell harvest will occur during hematopoietic recovery following the 2nd cycle of Induction therapy. Surgery to resect any accessible residual tumor will occur following the fifth cycle of Induction therapy. Patients proceed to ablative Consolidation therapy at completion of Induction if they have an immunocytologically negative stem cell product available. Consolidation therapy will consist of the myeloablative regimen of carboplatin, etoposide, and melphalan followed by aggressive local irradiation designed to attempt to decrease the local relapse rate as is currently utilized on A3973. G-CSF will be given post-transplant from the day of stem cell infusion until the absolute neutrophil count (ANC) is greater than or equal to 2000/ L for three consecutive days. Post-transplant Maintenance therapy with six cycles of 13-cis-retinoic acid will be given starting at approximately Day 66 post stem cell transplan

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000048-45
Application #
7376886
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
2005-12-01
Project End
2006-11-30
Budget Start
2005-12-01
Budget End
2006-11-30
Support Year
45
Fiscal Year
2006
Total Cost
$20,695
Indirect Cost
Name
Northwestern University at Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Sherenian, Michael G; Singh, Anne M; Arguelles, Lester et al. (2018) Association of food allergy and decreased lung function in children and young adults with asthma. Ann Allergy Asthma Immunol 121:588-593.e1
Baron, Kelly Glazer; Reid, Kathryn J; Malkani, Roneil G et al. (2017) Sleep Variability Among Older Adults With Insomnia: Associations With Sleep Quality and Cardiometabolic Disease Risk. Behav Sleep Med 15:144-157
Gupta, Ruchi S; Walkner, Madeline M; Greenhawt, Matthew et al. (2016) Food Allergy Sensitization and Presentation in Siblings of Food Allergic Children. J Allergy Clin Immunol Pract 4:956-62
Raghanti, Mary Ann; Edler, Melissa K; Stephenson, Alexa R et al. (2016) Human-specific increase of dopaminergic innervation in a striatal region associated with speech and language: A comparative analysis of the primate basal ganglia. J Comp Neurol 524:2117-29
Slama, Laurence; Jacobson, Lisa P; Li, Xiuhong et al. (2016) Longitudinal Changes Over 10 Years in Free Testosterone Among HIV-Infected and HIV-Uninfected Men. J Acquir Immune Defic Syndr 71:57-64
Makhija, Melanie M; Robison, Rachel G; Caruso, Deanna et al. (2016) Patterns of allergen sensitization and self-reported allergic disease in parents of food allergic children. Ann Allergy Asthma Immunol 117:382-386.e1
Ye, Wen; Rosenthal, Philip; Magee, John C et al. (2015) Factors Determining ?-Bilirubin Levels in Infants With Biliary Atresia. J Pediatr Gastroenterol Nutr 60:659-63
Arroyo-Ávila, Mariangelí; Santiago-Casas, Yesenia; McGwin Jr, Gerald et al. (2015) Clinical associations of anti-Smith antibodies in PROFILE: a multi-ethnic lupus cohort. Clin Rheumatol 34:1217-23
Lertratanakul, Apinya; Wu, Peggy; Dyer, Alan R et al. (2014) Risk factors in the progression of subclinical atherosclerosis in women with systemic lupus erythematosus. Arthritis Care Res (Hoboken) 66:1177-85
Nodzenski, Michael; Muehlbauer, Michael J; Bain, James R et al. (2014) Metabomxtr: an R package for mixture-model analysis of non-targeted metabolomics data. Bioinformatics 30:3287-8

Showing the most recent 10 out of 189 publications