Grants

GRANTS FUNDED

Neuroblastoma and Medulloblastoma Translational Research Consortium
“A Phase II Preventative Trial of DFMO as a Single Agent in Patients with High Risk Neuroblastoma in Remission”
$25,000
10/01/2013-12/31/2019

Neuroblastoma and Medulloblastoma Translational Research Consortium
“A Phase II Trial of Nifurtimox for Refractory or Relapsed Neuroblastoma and Relapsed Medulloblastoma”
$15,000
02/01/2014-02/28/2019

Neuroblastoma and Medulloblastoma Translational Research Consortium
“Molecular-Guided Therapy for the Treatment of Patients with Relapssed and Refractory Childhood Cancer”
$41,000
04/01/2014-04/03/2019

CSK/Novartis
“A Phase II Study of Pazopanib GW786034, NSC# 737754 in Children, Adolescents and Young Adults with Refractory Solid Tumors”
$39,700
03/01/2015-03/31/2019

Neuroblastoma and Medulloblastoma Translational Research Consortium
“PEDS-PLAN – Pediatric Precision Laboratory Advanced Neuroblastoma Therapy; A Pilot Study Using Molecular Guided Therapy with Induction Chemotherapy Followed by Maintenance with DFMO for Subjects with Newly Diagnosed High-Risk Neuroblastoma”
$13,000
10/01/2015-10/30/2018

F. Hoffmann-La Roche Ltd
“An Early Phase, Multicenter, Open-Label Study of the Safety and Pharmacokinetics of Atezolizumab (MPDL3280A) in Pediatric and Young Adult Patients with Previously Treated Solid Tumors”
$68,214
11/14/2015-11/30/2023

Celgene, Inc
“A Phase 2, Multicenter, Single-Arm, Open Label Study to Evaluate the Activity, Safety and Pharmokinetics of Lenalidomide (Revlimid®) in Pediatric Subjects from 1 to ≤18 Years of Age with Relapsed or Refractory Acute Myeloid Leukemia”
$45,000
11/25/2015-11/30/2020

Pediatric Oncology Experimental Therapeutics Investigators’ Consortium (POETIC)
“Phase I Study of Cafrilzomib in Combination with Cyclophosphamide and Etoposide for Children with Relapsed and Refractory Solid Tumors”
$56,058
02/03/2016-02/28/2019

F. Hoffmann-La Roche Ltd.
“A Phase I/II Multicenter, Open-Label, Dose Escalation Study of the Safety and Pharmacokinetics of Cobimetinib in Pediatric and Young Adult Patients with Previously Treated Solid Tumors”
$46,258
03/14/2016-03/31/2019

Neuroblastoma and Medulloblastoma Translational Research Consortium
“NMTT – Neuroblastoma Maintenance Therapy Trial Using Difluoromethylornithine (DFMO)”
$35,000
03/14/2016-03/31/2023

Incyte, Inc.
“A Phase 2 Study of the JAK1/JAK2 Inhibitor Ruxolitinib with Chemotherapy in Children with De Novo High-Risk CRLF2- Rearranged and/or JAK Pathway – Mutant Acute Lymphoblastic Leukemia”
$14,500
01/23/2017-01/31/2021

BMS
“Risk-based, response-adapted, Phase II open-label trial of Nivolumab + Brentuximab vedotin (N + Bv) for children, adolescents, and young adults with relapsed/refractory (R/R) CD30 + classic Hodgkin lymphoma (cHL) after failure of first-line therapy, followed by Brentuximab + bendamustine (Bv + B) for participants with a suboptimal response”
$33,000
08/15/2017-08/31/2022

Pediatric Oncology Experimental Therapeutics Investigators’ Consortium (POETIC)
“A Phase I/II Study of Neratinib in Pediatric Patients with Relapsed or Refractory Solid Tumors or Hematologic Malignancies”
$66,476
08/28/2017-08/31/2022

CURRENT RESEARCH

Under Dr. Brown’s leadership, the early phase clinical research enterprise was expanded and re-organized and the Experimental Therapeutics Research and Clinical Team (ExTRaCT) was established. The mission of this Experimental Therapeutics Program is to provide novel, biologically relevant treatment regimens that incorporate cutting-edge science to pediatric and AYA patients with cancer with the goal of becoming a leader of Phase I/II Clinical Trials site.

The makeup of ExTRaCT includes 6 physicians, 1 nurse practitioner, 1 clinical specialist pharmacist, 1 clinical research nurse and 1 regulatory/compliance specialist all within the Division of Pediatric Hematology/Oncology. The objectives of ExTRaCT is to identify and expedite screening of potential patients for participation in early phase clinical trials, consult and consent potential early phase study patients and their families, participate in a “shared-care” model with the patients’ primary oncologists, and to ensure thorough documentation.

In addition, ExTRaCT members help identify and implement innovative early phase clinical studies, develop SOP’s and policies for the Experimental Therapeutics Program, develop strategies to increase visibility of ExTRaCT to the entire Penn State Health community as well as regionally and nationally, educate and act as role models for fellows and peers and identify opportunities for scholarly work.

Also under Dr. Brown’s direction, in 2014, Penn State Hershey became a member of the Neuroblastoma and Medulloblastoma Translational Research Consortium (NMTRC). The NMTRC is a network of more than 20 universities, children’s hospitals, and institutions that offers a number of early phase clinical trials including one clinical trial using a very novel, individualized approach of determining the treatment plan based upon the unique biologic properties of the tumor itself. For a number of different cancer types, relapsed or refractory disease is typically incurable with today’s therapies.

In this study led by the NMTRC, biopsies of the patient’s tumor(s) are obtained and then sent to TGen for sophisticated, cutting-edge genomic analysis of the individual tumor. Based on the molecular aberrations within the tumor, a report that predicts potential response of the individual tumor to over 200 drugs and naturally occurring compounds is generated. Then, a panel of NMTRC members, consisting of pediatric oncologists, pharmacists, pathologists and scientists, holds a “virtual tumor board” during which time the patient’s clinical course is reviewed, the results of the report discussed and a molecularly guided treatment plan (that is based upon the specific tumor analysis) is devised. Then, the patient begins his/her personalized, molecularly guided therapy.

SELECTED PUBLICATIONS

The following are publications of Dr. Brown since 2012:

Lund TC, Woo K, Tecca HR, Hilgers MV, Abdel-Azim H, Abraham A, Angel Diaz M, Badawy SM, Broglie L, Brown V, Dvorak CC, Gonzalez-Vincent M, Hashem H, Hayashi RJ, Jacobsohn DA, Kent MW, Li C-k, Margossian SB, martin, Mehta P, Myets K, Olsson R, Page K, Pulsipher MA, Shaw PJ, Smith AR, Triplett BM, Verneris MR, Eapen M: Outcomes after Second Hematopoietic Cell Transplantations in Children and Young Adults with Relapsed Acute Leukemia. Biology of Blood and Marrow Transplantation, 25(2): 301-6, February 2019. PMID: 30244103

Ustun C, Young JH, Papanicolaou GA, Kim S, Ahn KW, Chen M, Abdel-Azim H, Alijurf M, Beitinjaneh A, Brown V, Cerny J, Chhabra S, Kharfan-Dabaja MA, Dahi PB, Daly A, Dandoy CE, Dvorak CC, Freytes CO, Hashmi S, Lazarus H, Ljungman P, Nishihori T, Page K, Pingali SPK, Saad A, Savani BN, Weisdorf D, Williams K, Wirk B, Auletta JJ, Lindermans CA, Komanduri K, Riches M: Bacterial Blood Stream Infections (BSIs), Particularly Post-Engraftment BSIs, are Associated with Increased Mortality after Allogeneic Hematopoietic Cell Transplantation. Bone Marrow Transplantation, Dec 13, 2018 [Epub ahead of print]. doi: 10.1038/s41409-018-0401-4 PMID: 30546070

Sholler GLS, Ferguson W, Bergendahl G, Bond JB, Neville K, Eslin D, Brown V, Roberts W, Wada K, Oesterheld J, Mitchell D, Foley J, Parikh NS, Eshun F, Zage P, Rawwas J, Sencer S, Pankiewicz D, Quinn M, Rich M, Junewick J, Kraveka JM: Maintenance DFMO Increases Survival in High Risk Neuroblastoma. Scientific Reports, 8(1):14445, Sept 27, 2018. PMID: 30262852

Slayton W, Schultz K, Kairalla JA, Devidas M, Mi X, Pulsipher M, Chang BH, Mulligan CG, Iacobucci I, Silverman LB, Borowitz MJ, Carroll AJ, Heerema NA, Gastier-Foster JM, Wood BL, Mizrahy SL,Merchant TE, Brown VI, Sieger L, Siegal MJ, Raetz EA, Winick NJ, Loh ML, Carroll WL, Hunger SP: Dasatinib plus intensive chemotherapy in children, adolescents, and young adults with Philadelphia chromosome positive acute lymphoblastic leukemia: Results of Children’s Oncology Group trial AALL0622. J Clinical Oncology, 36 (22):23-06-14, Aug 1, 2018, PMID: 29812996

Bitan M, Ahn KW, Millard HR, Pulsipher MA, Abdel-Azim H, Auletta JJ, Brown VI, Chan KW, Diaz MA, Dietz A, Vincent MG, Guilcher G, Hale G, Hayashi RJ, Keating A, Mehta P, Myers K, Page K, Prestige T, Shah N, Smith AR, Woolfrey A, Thiel E, Davies SM, Eapen M: Personalized Prognostic Risk Score for Long-Term Survival for Children with Acute Leukemia after Allogeneic Transplant. Biology of Blood and Marrow Transplantation, 23 (9): 1523-30, Sept 2017. (PMID: 28527984)

Khandelwal P, Millard HR, Thiel E, Abdel-Azim H, Abraham AA, Auletta JJ, Boulad F, Brown VI, Camitta BM, Chan KW, Chaudhury S, Cowan MJ, Angel-Diaz M, Gadalla SM, Gale RP, Hale G, Kasow KA, Keating AK, Kitko CL, MacMillan ML, Olsson RF, Page KM, Seber A, Smith AR, Warwick AB, Wirk B, Mehta PA: Hematopoietic Stem Cell Transplantation Activity in Pediatric Cancer between 2008 and 2014 in the United States: A CIBMTR Report. Biology of Blood and Marrow Transplantation, 23(8): 1342-9, Aug 2017. (PMID:28450183)

Burke MJ, Verneris MR, Le Rademacher J, He W, Abdel-Azim H, Abraham AA, Auletta JJ, Ayas M, Brown VI, Cairo MS, Chan KW, Diaz Perez MA, Dvorak CC, Egeler RM, Guilcher GMT, Hayashi RJ, Kasow KA, Leung WH, Olsson RF, Pulsipher MA, Shah NN, Thiel E, Kitko CL: Transplant Outcomes for Children with T-Cell Acute Lymphoblastic Leukemia in Second Remission: A Report of the CIBMTR®. Biology of Blood and Marrow Transplantation, 21(12): 2154-9, Dec 2015. (PMID: 26327632)

Brown V.I.: Entry on “Graft versus Host Disease”. In: The 5 Minute Pediatric Consult, 7th Edition. Michael D. Cabana, et al (eds.). Lippincott Williams and Wilkins, Baltimore, MD, in press.

Maheshwari S, Kassim A, Yef RF, Domm J, Calder C, Evans M, Manes B, Bruce K, Brown V, Ho R, Frangoul H, Yang E: Targeted Busulfan therapy with a steady-state concentration of 600- 700 ng/mL in patients with sickle cell disease receiving HLA-identical sibling bone marrow transplant. Bone Marrow Transplantation, 49(3):366-9, Mar 2014. (PMID: 24317124)

Frangoul H, Min E, Wang W, Chandrasekhar R, Calder C, Evans M, Manes B, Bruce K, Brown V, Ho R, Domm J: Incidence and risk factors for hypogammaglobulinemia in pediatric patients following allo-SCT. Bone Marrow Transplantation, 48(11):1456-9, 2013. (PMID:23708706)

Barrett D, Brown VI, Grupp SA, Teachey DT: Targeting the PI3K/Akt/mTOR Signaling Axis in Children with Hematologic Malignancies. Pediatric Drugs, 14(5):299-316, 2012. (PMID: 22845486)

Dinardo L, Brown, V, Perez E, Brunin N, Sullivan K: A Single Center Study of Hematopoietic Stem Cell Transplantation for Primary Immune Deficiencies (PIDD). Pediatric Transplantation, 16(1):63-72, 2012.

Valerie I. Brown, M.D., Ph.D.