This study investigated the influence of the Iowa Association of School Administrators (ASA), the Iowa Association of School Boards (IASB), and the Iowa State Education Association (ISEA) in ...determining educational policy in the first session of the 70th Iowa General Assembly. Specific research questions asked how legislators' opinions of influence varied in regard to selected demographic characteristics of the legislators. The 100 representatives in the House and the 50 members of the Senate of the first session of the 70th General Assembly served as the population for the study. The sample consisted of 132 representatives and senators (88% of the House and 88% of the Senate). Data were collected by interviewing legislators during the first session. Interview questions asked the legislators to state their opinions about the influence of educational interest groups in determining educational policy. In addition, legislators were asked to compare the IASA, IASB, and ISEA in a number of areas including credibility, prestige, electoral influence in the home district, and overall influence in the legislature. A structured format was used for each interview. Each legislator heard the same questions verbatim, and responses were selected from those provided by the interviewer. Responses were analyzed by comparing the frequency of responses from demographically designated groups of legislators. A chi-square analysis was used to determine which demographic factors were related. In the opinions of the legislators in the sample, educational interest groups were one of the most important sources of influence in the legislature in matters of educational policy. The three groups in the study were not equal in influence in the opinions of the legislators, and the amounts of influence assigned to each organization varied according to the selected characteristics of the legislators. The political party, more than other legislator characteristics, accounted for differences in legislators' opinions. Other factors which accounted for differences were found to be highly correlated with political party. The ISEA was selected by legislators as most influential organization overall. The IASB was rated second. The IASA was considered least influential by the legislators.
Abstract BACKGROUND Atypical choroid plexus papilloma (ACPP) and choroid plexus carcinoma (CPC) are rare malignant tumors of the central nervous system. Complete resection, the most important ...prognostic variable for long-term survival, is often limited by tumor vascularity and voluminous size in children. While systemic chemotherapy is known to reduce tumor volume and intra-operative blood loss, children often experience dose-limiting side effects. We hypothesize the use of intra-arterial (IA) chemotherapy for newly diagnosed, recurrent, or residual CPC/ACPP would increase likelihood of achieving complete resection in a safer manner. OBJECTIVE To assess the safety, feasibility, and effect of pre-operative IA chemotherapy for CPC/ACPP. METHOD The patient was treated according to phase I clinical trial protocol (NCT04994977) which consists of a single IA chemotherapy administration of melphalan, topotecan, and carboplatin followed by MRI-based response assessment to determine eligibility for second-look surgery. Primary endpoints are serious adverse events, and secondary endpoints include angiographic procedural success, tumor volume reduction on MRI, extent of resection and caclulated blood loss (CBL), and pathologic correlates of vascularity and tumor viability. RESULT 7-year-old male with Li-Fraumeni syndrome was enrolled for residual CPC (4.8 x 4.6 cm) after three prior resection attempts were limited by significant blood loss. Pre-operative IA chemotherapy was delivered to two targets without complication: the right posterolateral and anterior choroidal arteries. Five weeks later, MRI confirmed tumor volume reduction of 6.3%. On angiographic evaluation for administration of pre-surgical embolization, a significant reduction in angiographic hypervascularity was found, and liquid embolic embolization was not pursued. Craniotomy resulted in gross total resection without transfusion requirement and minimal CBL. Pathology demonstrated reduced proliferative index (Ki67 4% versus 10% in prior tissue). CONCLUSION Early phase results indicate pre-operative IA chemotherapy for residual CPC/ACPP may serve as safer bridge to second look surgery by decreasing tumor volume and vascularity.
Background Despite advances, multiple myeloma (MM) remains an incurable disease and resistance mechanisms are emerging. ISB 2001 has been designed to overcome those resistance mechanisms inherent to ...current MM therapies such as monoclonal antibodies (e.g. daratumumab), BCMA-targeted therapies, proteasome inhibitors(PIs), or immunomodulatory drugs(IMiDs). ISB 2001 is a first in class Trispecific T cell engager (TCE) that redirects cytotoxic T cells to BCMA and/or CD38 expressing myeloma cells. Simultaneous targeting of the two tumor associated antigens (TAA) may increase binding to tumor cells through avidity even with heterogeneous or low expression of the targeted TAA (BCMA or CD38). Therefore, it may overcome tumor escape mechanisms associated with low tumor antigenic expression inherent to current MM targeted therapies. Preclinically, ISB 2001 has demonstrated improved activity when compared to other BCMA or CD38 targeted molecules either alone or in combination across different MM models (M. Pihlgren et al., Blood. 140, 858-859 (2022), M. Pihlgren et al., Cancer Res. 83, 2970-2970 (2023)). Study design and methods This first-in-human, multicenter, open label Phase 1 study is assessing the safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of ISB 2001 in relapsed/refractory multiple myeloma (RRMM) patients. This study will enroll subjects treated with prior IMiDs, PIs, and anti-CD38 therapies, or intolerant of, established therapies known to provide benefit (prior BCMA therapies, or prior transplantation and cellular therapies allowed).be conducted in two parts (Part 1: Dose escalation and Part 2: Dose expansion) (Figure 1). Criteria for enrollment in this study include patients with RRMM with measurable disease who have been treated with an anti-CD38 antibody, IMiDs, PIs either in combination or as a single agent, and /or intolerant of established therapies known to provide clinical benefit. ISB 2001 is being administered weekly by subcutaneous (SC) injection in 28-day cycles, with two step-up doses on cycle 1 day 1 (C1D1) and C1D4 before administering the full dose on C1D8. The first-in-human dose was derived by integrating both in vitro and in vivo preclinical data benchmarked to teclistamab utilizing a quantitative systems pharmacology (QSP) model guided approach. The fractionated step-up dosing before administering the full dose on C1D8 was included in every cohort preemptively to minimize the potential cytokine release syndrome (CRS) risk. The study will follow a rapid titration single patient dose escalation design until the completion of cohort 3 or until one of the safety conversion criteria are met, whichever comes first, after which the design will be converted to a conventional 3+3 dose escalation. The primary outcome measure is the number of DLTs during the first 28 days after the first study treatment (ie, Cycle 1) in each cohort. Once a potential safe and efficacious dose range is identified, the Part 2 expansion will start enrollment in two arms at two putative recommended Part 2 doses with 1:1 randomization with at least 20 patients per arm (FDA Project Optimus). The primary objective of Part 2 is to confirm safety and to select the recommended Phase 2 dose (RP2D). Secondary endpoints include PK parameters, immunogenicity incidence, ORR, CRR and DOR based on IMWG criteria. Exploratory endpoints include levels of cytokines, chemokines, sCD38, sBCMA, APRIL and BAFF in peripheral blood, immunophenotyping in peripheral blood and bone marrow, and MRD negative rate. Approximately 40 patients will be enrolled in Part 1 at sites in Australia, France and the United States. A total of approximately 40 evaluable patients will be enrolled in Part 2. The study is currently open for enrollment (Clinicaltrials.gov identifier: NCT05862012).
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