Browsing by Author "Peters, Katherine"

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    CTIM-10. REPRODUCIBILITY OF CLINICAL TRIALS USING CMV-TARGETED DENDRITIC CELL VACCINES IN PATIENTS WITH GLIOBLASTOMA
    (Neuro-Oncology, 2021-11-12) Batich, Kristen; Mitchell, Duane; Healy, Patrick; Herndon, James; Broadwater, Gloria; Michael, Gunn; Huang, Min-Nung; Hotchkiss, Kelly; Sanchez-Perez, Luis; Nair, Smita; Congdon, Kendra; Norberg, Pam; Weinhold, Kent; Archer, Gary; Reap, Elizabeth; Xie, Weihua; Shipes, Steven; Albrecht, Emily; Peters, Katherine; Randazzo, Dina; Johnson, Margaret; Landi, Daniel; Desjardins, Annick; Friedman, Henry; Vlahovic, Gordana; Reardon, David; Vredenburgh, James; Bigner, Darell; Khasraw, Mustafa; McLendon, Roger; Thompson, Eric; Cook, Steven; Fecci, Peter; Codd, Patrick; Floyd, Scott; Reitman, Zachary; Kirkpatrick, John; Friedman, Allan; Ashley, David M; Sampson, John
    Abstract INTRODUCTION Vaccination with dendritic cells (DCs) fares poorly in primary and recurrent glioblastoma (GBM). Moreover, GBM vaccine trials are often underpowered due to limited sample size. METHODS To address these limitations, we conducted three sequential clinical trials utilizing Cytomegalovirus (CMV)-specific DC vaccines in patients with primary GBM. Autologous DCs were generated and electroporated with mRNA encoding for the CMV protein pp65. Serial vaccination was given throughout adjuvant temozolomide cycles, and 111Indium radiolabeling was implemented to assess migration efficiency of DC vaccines. Patients were followed for median overall survival (mOS) and OS. RESULTS Our initial study was the phase II ATTAC study (NCT00639639; total n=12) with 6 patients randomized to vaccine site preconditioning with tetanus-diphtheria (Td) toxoid. This led to an expanded cohort trial (ATTAC-GM; NCT00639639) of 11 patients receiving CMV DC vaccines containing granulocyte-macrophage colony-stimulating factor (GM-CSF). Follow-up data from ATTAC and ATTAC-GM revealed 5-year OS rates of 33.3% (mOS 38.3 months; CI95 17.5-undefined) and 36.4% (mOS 37.7 months; CI95 18.2-109.1), respectively. ATTAC additionally revealed a significant increase in DC migration to draining lymph nodes following Td preconditioning (P=0.049). Increased DC migration was associated with OS (Cox proportional hazards model, HR=0.820, P=0.023). Td-mediated increased migration has been recapitulated in our larger confirmatory trial ELEVATE (NCT02366728) of 43 patients randomized to preconditioning (Wilcoxon rank sum, Td n=24, unpulsed DC n=19; 24h, P=0.031 and 48h, P=0.0195). In ELEVATE, median follow-up of 42.2 months revealed significantly longer OS in patients randomized to Td (P=0.026). The 3-year OS for Td-treated patients in ELEVATE was 34% (CI95 19-63%) compared to 6% given unpulsed DCs (CI95 1-42%). CONCLUSION We report reproducibility of our findings across three sequential clinical trials using CMV pp65 DCs. Despite their small numbers, these successive trials demonstrate consistent survival outcomes, thus supporting the efficacy of CMV DC vaccine therapy in GBM.
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    CTIM-21. PEPTIDE VACCINE DIRECTED TO CMV pp65 FOR TREATMENT OF RECURRENT MALIGNANT GLIOMA AND MEDULLOBLASTOMA IN CHILDREN AND YOUNG ADULTS: PRELIMINARY RESULTS OF A PHASE I TRIAL
    (Neuro-Oncology, 2020-11-09) Thompson, Eric; Landi, Daniel; Lipp, Eric; Balajonda, Bea; Herndon, James; Buckley, Evan; Flahiff, Charlene; Jaggers, Denise; Schroeder, Kristin; Randazzo, Dina; Desjardins, Annick; Johnson, Maggie; Peters, Katherine; Khasraw, Mustafa; Malinzak, Michael; Mitchell, Duane; Ashley, David; Sampson, John
    Abstract INTRODUCTION The cytomegalovirus (CMV) antigen, pp65, is ubiquitously expressed in malignant glioma and medulloblastoma but not in healthy brain. The objective of this Phase I trial (NCT03299309) was to assess the safety and feasibility of a novel pp65 peptide vaccine (PEP-CMV) in children and young adults with recurrent medulloblastoma and malignant glioma. METHODS Vaccines contain a synthetic long peptide (SLP) of 26 amino acids encoding multiple potential class I, class II, and antibody epitopes of CMV pp65 across several haplotypes. This SLP is administered as an emulsion in Montanide ISA 51. Patients receive a single course of temozolomide to induce lymphopenia, tetanus/diphtheria toxoid site preconditioning, then vaccines administered intradermally every two weeks for 3 doses, then monthly. RESULTS To date, 17 patients have been enrolled. Diagnoses include medulloblastoma (n=1), glioblastoma (n=9), anaplastic oligodendroglioma (n=2), anaplastic astrocytoma (n=2), and malignant glioma NOS (n=3). Mean number of prior treatment regimens is 4.9 (range 1–12). Mean age is 22yo (range 6–35) and 41% of patients are male. The median KPS is 80. The median number of vaccines given at time of analysis is 3.3 (range 1–12). There have been no ≥ 3 Grade toxicities related to the vaccine. One patient developed nausea, vomiting, palpitations, and tachycardia after vaccination and had elevated inflammatory cytokines consistent with cytokine release syndrome. Median PFS is 2.5 months (95% CI: 0.8, not estimable) and median OS is 6.5 months (95% CI 1.8, not estimable). Interim analysis of immune monitoring bloodwork and perfusion MRI to quantify responses to PEP-CMV has been delayed due to COVID-19. However, adults with GBM who received PEP-CMV (NCT02864368) had significant (p≤0.05) increases in GCSF, GM-CSF, IFN-γ, IL-10, IL-2, IL-8, MIP1-α, and TNF-α levels. CONCLUSIONS Preliminary results demonstrate that PEP-CMV is feasible and well-tolerated in heavily pretreated, multiply recurrent patients.
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    HOUT-21. CHARACTERISTICS OF SHORT-TERM SURVIVAL IN PATIENTS WITH GLIOBLASTOMA: A RETROSPECTIVE ANALYSIS
    (Neuro-Oncology, 2019-11-11) Barbour, Andrew; Healy, Patrick; Lipp, Eric; Herndon, James; Thomas, Leslie; Johnson, Margaret; Ashley, David; Desjardins, Annick; Randazzo, Dina; Friedman, Henry; Kirkpatrick, John; Peters, Katherine
    Abstract We sought to identify characteristics of glioblastoma (GBM) patients with short survival (< 10 months) in order to identify prognostic factors useful for guiding treatment management. This is an IRB-approved retrospective analysis of adult newly diagnosed GBM patients from 2008–2016 who survived < 10 months from diagnosis. We extracted demographics, tumor characteristics, and treatment details. We calculated survival from surgical diagnosis to date of death. The cohort includes 197 subjects (61% male) with a median age of 68 years (range 19–94). The majority (93%) are non-Hispanic white. The cohort has a median survival of 144 days (95% CI: 130–160). We focused on traditional prognostic indicators, including extent of surgical resection and KPS. A majority had biopsy only (n=92, 46.7%) rather than gross total (n=59, 29.9%) or subtotal (n=46, 23.4%) resection. Moreover, 160 out of 197 patients had a documented KPS with a majority being below 90 (KPS=70–80 (n=96); KPS < 70 (n=31)). Of 179 patients with data on RT course, 18% (n=32) received no RT or opted for hospice after diagnosis, 3% (n=6) received only RT, 54% (n=97) received RT+temozolomide (TMZ), and 24% (n=43) received RT+TMZ+bevacizumab. Of the 147 subjects receiving RT, 79% completed their RT course as prescribed. Most commonly, RT was prescribed as a 6- to 6-1/2-week course (85%), typically 59.4 Gy (45Gy primary, 14.4Gy boost) over 33 fractions or 60 Gy over 30 fractions. In contrast, 15% received a 3-week RT course, typically scheduled as 15 fractions of 2.667 Gy. We concluded that GBM patients with survival < 10 months were more likely to have biopsy only and a KPS < 90, notably associated with poorer prognosis. We continue to explore this dataset for further prognostic factors, particularly inability to complete planned RT course, and are comparing these traits to a larger cohort.
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    INNV-20. RADIOGRAPHIC RESPONSE AND SEIZURE CONTROL IN IDH1 MUTANT GLIOMA PATIENTS USING IVOSIDENIB
    (Neuro-Oncology, 2021-11-12) Peters, Katherine; Patel, Mallika; Alford, Candice; Chavez, Gerardo; Kim, Jung-Young; Durling, Jennifer; Novack, Tracy; Batich, Kristen; Shoaf, Madison; Hanzlik, Emily; Affronti, Mary; Johnson, Margaret; Landi, Daniel; Khasraw, Mustafa; Desjardins, Annick; Friedman, Henry; Ashley, David M
    Abstract Isocitrate dehydrogenase 1 (IDH1) is commonly mutated in grade II-III gliomas, and the mutant enzyme leads to the production of the oncometabolite 2-hydroxyglutarate (2-HG). 2-HG is responsible for the gliomagenesis associated with these tumors and the promotion of seizures via glutamate receptors. Ivosidenib, a small molecule oral mIDH1 inhibitor, has shown promise in clinical trials to treat IDH1 mutant gliomas, and providers can utilize this agent in IDH1 mutant glioma patients. We evaluated our IDH1 mutant glioma patients treated off-label with ivosidenib and described the radiographic response and seizure control in this cohort when ivosidenib was initiated between October 2020 to February 2021. Radiographic response was determined using RANO criteria, and seizure control was determined by comparing seizures per month before and after initiation of ivosidenib. All patients represented received single-agent ivosidenib dosed at 500 mg orally once a day. One patient required a dose reduction to 250 mg orally once a day because of drug-induced diarrhea. In our cohort of six patients, patient age range was 31 to 74 years with four female patients and two male patients. Diagnoses represented were astrocytoma, IDH1 mutant (n=3) oligodendroglioma (WHO), IDH1 mutant, 1p19q co-deleted (n=2), and anaplastic astrocytoma IDH1 mutant (n=1). Three patients experienced a reduction of seizure frequency, two patients did not have seizures before or after therapy, and one patient remained with the same level of seizures (1 seizure/month). Radiographic responses recorded included three patients with stable disease, two patients with minor responses, and one patient with a partial response. Treatment with ivosidenib is ongoing for this cohort of mIDH1 glioma patients. Updated information on prolonged disease control and seizure control in this cohort of IDH1 mutant glioma patients will be presented. Therapeutics, such as ivosidenib, can lead to improved seizure control and radiographic outcomes in IDH1 mutant glioma patients.
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    INNV-31. NEURO-ONCOLOGY OUTPATIENT SATISFACTION IS MAINTAINED IN THE ERA OF COVID-19 TELEMEDICINE
    (Neuro-Oncology, 2021-11-12) Petitt, Zoey; Herndon, James; Gottfried, Oren; Cone, Christina; Landi, Daniel; Khasraw, Mustafa; Friedman, Henry; Ashley, David M; Desjardins, Annick; Peters, Katherine; Johnson, Margaret
    Abstract INTRODUCTION The use of telemedicine increased during the COVID-19 pandemic. However, the impact on patient satisfaction in the Neuro-oncology population is unknown. This quality improvement project compares outpatient satisfaction before and during the COVID-19 pandemic as well as in-person versus telemedicine platforms during the pandemic. METHODS We performed an IRB-exempt retrospective analysis of aggregate de-identified outpatient satisfaction scores among Neuro-oncology patients seen at The Preston Robert Tisch Brain Tumor Center (PRTBTC) at Duke University. The Clinician & Group Consumer Assessment of Healthcare Providers and Systems (CG-CAHPS) is a survey developed and distributed by Press Ganey Associates, and is the most widely used outpatient satisfaction survey in the United States. We compared pre-COVID-19 CG-CAHPS scores from patients who received in-person care at the PRBTC between April 2019 and March 2020 to COVID-19 pandemic CG-CAHPS scores (i.e. those who received either telemedicine or in-person care at the PRTBTC) from April 2020 to March 2021. RESULTS Approximately 1448 surveys were completed for both in-person and telemedicine visits. During the pandemic, 48.6% of surveys represented telemedicine, with monthly variations from 84.6% (April 2020) to 21.4% (March 2021). Patient satisfaction scores pre-COVID-19 were similar to those during the pandemic: overall provider rating from 0-10 (9.28 v 9.36), knowledge of medical history (96.9% v 95.4%), listens carefully (96.6% v 96.9%), shows respect (97.2% v 98.1%), and time spent (93.2% v 95.5%). During the COVID-19 pandemic, in-person and telemedicine demonstrate similar levels of satisfaction: overall provider rating from 0-10 (9.29 v 9.48), knowledge of medical history (94.9% v 96.1%), listens carefully (95.4% v 99.0%), shows respect (97.5% v 99.0%), and time spent (94.7% v 96.7%). CONCLUSION Outpatient satisfaction prior to and during the COVID-19 pandemic was similar. Patients reported similar satisfaction between in-person and telemedicine platforms. We support the ongoing use of telemedicine for outpatient Neuro-oncology.
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    QOLP-10. A LONGITUDINAL OBSERVATIONAL STUDY OF EXERCISE BEHAVIOR IN GLIOBLASTOMA PATIENTS TREATED WITH TUMOR-TREATING FIELDS
    (Neuro-Oncology, 2021-11-12) Peters, Katherine; Affronti, Mary; Kim, Jung-Young; Patel, Mallika; Johnson, Margaret; Bartlett, David; Cort, Nicole; Lipp, Eric; Iden, Deborah; Broadwater, Gloria; Herndon, James; Landi, Daniel; Khasraw, Mustafa; Desjardins, Annick; Friedman, Henry; Ashley, David M
    Abstract Glioblastoma (GBM) patients can use tumor-treating fields (TTFs) with adjuvant temozolomide (TMZ) to treat their disease. TTFs involve wearing transfixed transducers to the shaved scalp, and the transducers are wired to a battery pack that is either fixed or carried (weighing 2.7 pounds). EF-14 clinical trial did evaluate health-related quality of life with standardized patient-report outcome measures but did not measure exercise behavior. We sought to evaluate the exercise behavior of GBM patients using TTFs. We consented GBM patients who intended to use TTFs with adjuvant TMZ after completion of chemoradiation. After informed consent and before starting TTFs, patients completed a self-administered questionnaire, Godin Leisure-Time Exercise Questionnaire, to assess exercise behavior/physical function. To calculate our primary outcome of total exercise behavior, the frequency of exercise sessions per week within each intensity category was multiplied by the average reported duration, weighted by an estimate of the MET, summed across all intensities, and expressed as average MET-hr/wk. Prior work has defined that physical function can be compared as &lt; 9 MET-h/wk vs. ≥ 9 MET-h/wk. We evaluated at baseline and up to 24-week exercise behavior in patients with TTFs vs. historical controls not using TTFs. We enrolled 19 total GBM patients, with 14 proceeding to use TTFs. Of the 14 patients on TTFs, seven patients (50%) completed ≥ 9 MET-h/wk of exercise, and this level was maintained 8, 16, and 24 weeks after starting TTFs. Six months after the completion of chemoradiation, mean MET-h/wk was decreased in the TTFs group (n=6) (10.71 sd=7.06) vs. historical controls (n=38) (27.35 sd=46.94). TTFs did not interfere with exercise behavior in our GBM cohort, but when compared to GBM patients not utilizing TTFs, there could be a long-term impact on exercise behavior. More research is needed to evaluate exercise behavior in GBM patients using TTFs.