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  • American Society of Clinical Oncology (ASCO)  (14)
  • 1
    Online Resource
    Online Resource
    Elective Cancer Surgery in COVID-19–Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 1 ( 2021-01-01), p. 66-78
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 1 ( 2021-01-01), p. 66-78
    Abstract: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.20.01933
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 2
    Online Resource
    Online Resource
    Phase III Study of Two Different Dosing Schedules of Erythropoietin in Anemic Patients With Cancer
    American Society of Clinical Oncology (ASCO) ; 2006
    In:  Journal of Clinical Oncology Vol. 24, No. 7 ( 2006-03-01), p. 1079-1089
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 24, No. 7 ( 2006-03-01), p. 1079-1089
    Abstract: To compare maintenance epoetin alfa administered once every 3 weeks with continued weekly epoetin alfa for patients with cancer-associated anemia. Patients and Methods Eligible patients were randomly assigned at enrollment to receive three weekly doses of epoetin alfa 40,000 U subcutaneously (SC), followed by either standard weekly epoetin alfa (40K arm) or 120,000 U of epoetin alfa (120K arm) SC every 3 weeks for 18 additional weeks. Results Three hundred sixty-five patients were enrolled. One hundred eighty-three patients were assigned to the 40K arm, and 182 were assigned to the 120K arm. There was no difference in the proportion of patients requiring transfusions during the study (23% in 40K arm and 18% in 120K arm, P = .22) or specifically during the maintenance phase (13% in 40K arm v 15% in 120K arm, P = .58). Patients randomly assigned to the 40K arm were more likely to have a ≥ 2 or ≥ 3 g/dL hemoglobin (Hb) increment, were more likely to have a drug dose held because of high Hb, and had higher mean end-of-study Hb levels. Toxicities, including thromboembolism, and overall survival were similar. Patients in the 40K arm had a higher global quality of life (QOL) at baseline for unclear reasons, whereas patients in the 120K arm had a greater global QOL improvement during the study, so end-of-study QOL was equivalent. Conclusion After three weekly doses of epoetin alfa 40,000 U, a dose of 120,000 U can be administered safely once every 3 weeks without increasing transfusion needs or sacrificing QOL. The Hb increment is somewhat greater with continued weekly epoetin alfa. Lack of blinding as a result of different treatment schedules may have confounded results.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2005.02.7276
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2006
    detail.hit.zdb_id: 2005181-5
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  • 3
    Online Resource
    Online Resource
    Patient Knowledge and Expectations About Return of Genomic Results in a Biomarker-Driven Master Protocol Trial (SWOG S1400GEN)
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  JCO Oncology Practice Vol. 17, No. 11 ( 2021-11), p. e1821-e1829
    Details
    In: JCO Oncology Practice, American Society of Clinical Oncology (ASCO), Vol. 17, No. 11 ( 2021-11), p. e1821-e1829
    Abstract: Biomarker-driven master protocols represent a new paradigm in oncology clinical trials, but their complex designs and wide-ranging genomic results returned can be difficult to communicate to participants. The objective of this pilot study was to evaluate patient knowledge and expectations related to return of genomic results in the Lung Cancer Master Protocol (Lung-MAP). METHODS: Eligible participants with previously treated advanced non–small-cell lung cancer were recruited from patients enrolled in Lung-MAP. Participants completed a 38-item telephone survey ≤ 30 days from Lung-MAP consent. The survey assessed understanding about the benefits and risks of Lung-MAP participation and knowledge of the potential uses of somatic testing results returned. Descriptive statistics and odds ratios for associations between demographic factors and correct responses to survey items were assessed. RESULTS: From August 1, 2017, to June 30, 2019, we recruited 207 participants with a median age of 67, 57.3% male, and 94.2% White. Most participants “strongly/somewhat agreed” with statements that they “received enough information to understand” Lung-MAP benefits (82.6%) and risks (69.5%). In items asking about potential uses of Lung-MAP genomic results, 87.0% correctly indicated that the results help to select cancer treatment, but 〈 20% correctly indicated that the results are not used to confirm cancer diagnosis, would not reveal risk of developing diseases besides cancer, and would not indicate if family members had increased cancer risk. There were no associations between sociodemographic factors and proportions providing correct responses. CONCLUSION: In a large National Clinical Trials Network biomarker-driven master protocol, most participants demonstrated incorrect knowledge and expectations about the uses of genomic results provided in the study despite most indicating that they had enough information to understand benefits and risks.
    Type of Medium: Online Resource
    ISSN: 2688-1527 , 2688-1535
    URL: Article
    DOI: 10.1200/OP.20.00770
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 3005549-0
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  • 4
    Online Resource
    Online Resource
    Selumetinib in patients with tumors with MAPK pathway alterations: Results from Arm E of the NCI-COG pediatric MATCH trial.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. 10008-10008
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 10008-10008
    Abstract: 10008 Background: The NCI-Children’s Oncology Group (COG) Pediatric Molecular Analysis for Therapy Choice (MATCH) trial assigns patients age 1 to 21 years with relapsed or refractory solid tumors, lymphomas, and histiocytic disorders to phase 2 treatment arms of molecularly-targeted therapies based on genetic alterations detected in their tumor. Arm E evaluated the MEK inhibitor selumetinib (ARRY-142886) in patients whose tumors harbored activating alterations in the MAPK pathway ( ARAF, BRAF, HRAS, KRAS, NRAS, MAP2K1, GNA11, GNAQ hotspot mutations; NF1 inactivating mutations; BRAF fusions). Methods: Patients received selumetinib 25 mg/m2/dose (max 75 mg/dose) PO BID for 28-day cycles until disease progression or intolerable toxicity with response assessments obtained every 2-3 cycles. The primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival (PFS). Patients with low grade glioma were excluded. Results: A total of 21 patients (median age 14 years; range 5-21) were enrolled between 10/2017 and 8/2019, with 20 patients evaluable for response. Diagnoses were high grade glioma (HGG; n = 8), rhabdomyosarcoma (n = 7), adenocarcinoma (n = 2), and one each of MPNST, endodermal sinus/yolk sac tumor, plexiform neurofibroma (PN), and neuroblastoma. MAPK pathway alterations detected consisted of inactivating NF1 mutations (n = 8), hotspot mutations in KRAS (n = 8), NRAS (n = 3), and HRAS (n = 1), and BRAF V600E (n = 2). No objective responses were observed. Three patients had a best response of stable disease (HGG with NF1 mutation, 6 cycles; HGG with KRAS mutation, 12 cycles; PN with NF1 mutation, 13 cycles prior to removal for dose-limiting toxicity). Six-month PFS was 15% (95% CI: 4%, 34%). Adverse events that were deemed possibly, probably, or definitely attributable to study drug included one case each of grade 3 uveitis, lymphopenia, and thromboembolic event; one grade 4 CPK elevation; and one grade 5 thromboembolic event. Conclusions: Selumetinib did not result in tumor regression in this cohort of children and young adults with treatment-refractory tumors with activating MAPK pathway alterations. Of note, two patients with HGG initially had stable disease, but ultimately progressed after 6 and 12 cycles, respectively. Selumetinib has previously demonstrated activity in low grade glioma and PN and is now FDA-approved for PN. The results of our study indicate that MAPK pathway mutation status alone is insufficient to predict response to selumetinib monotherapy. It is likely that selumetinib and other MEK inhibitors will require combination with targeted or cytotoxic agents for optimal efficacy in children with persistent or progressive cancers after front-line chemotherapy. Clinical trial information: NCT03213691. Clinical trial information: NCT03155620.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.10008
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 5
    Online Resource
    Online Resource
    Factors impacting enrollment on NCI-COG Pediatric MATCH trial treatment protocols.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. 10007-10007
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 10007-10007
    Abstract: 10007 Background: The NCI-Children’s Oncology Group (COG) Pediatric Molecular Analysis for Therapy Choice (MATCH) trial assigns patients age 1 to 21 years with relapsed or refractory solid tumors, lymphomas, and histiocytic disorders to phase 2 treatment arms of molecularly-targeted therapies based on the genetic alterations detected in their tumor. Treatment arm assignments and enrollment decisions have now been made for 1000 study participants: we report here match and enrollment data and factors affecting treatment protocol enrollment. Methods: Patients enrolled in the Pediatric MATCH screening protocol were assigned to an open treatment protocol if an actionable mutation (aMOI) was detected by tumor DNA and RNA-based cancer gene panel sequencing. After a match, treatment protocol enrollment must occur within 8-12 weeks. Patient demographic data, reasons for not enrolling on treatment protocol (if applicable), and prior history of molecular testing were reported by study sites. The Fisher exact test was used to compare protocol enrollment rates between groups. Results: Results were analyzed for the first 1000 patients with testing completed (enrolled between July 2017 and October 2020). At least one tumor aMOI was detected in 310 (31%) patients and treatment protocol slots were available for 284 patients (28%). A total of 131 patients (46% of those matched) enrolled on a treatment arm. No difference in treatment protocol match or enrollment rate was observed for gender, race, or ethnicity. Both treatment protocol match rate (105/275, 38% vs 86/394, 22%) and enrollment rate (56/275, 20% vs 33/394, 8%) were significantly more frequent in patients with a reported history of prior molecular testing (p 〈 0.0001). The most common reasons provided for not enrolling on a treatment protocol were: patient receiving other treatment (32% of responses), poor clinical status (16%), lack of measurable disease (11%), or ineligible diagnosis for that treatment arm (10%). Ineligibility due to history of excluded prior targeted therapy (6%) or inability to swallow capsules (4%) was less frequent. Conclusions: The rate of Pediatric MATCH treatment protocol enrollment has exceeded pre-study projections, due to more frequent actionable mutation detection and treatment assignment than anticipated (28% observed, 10% projected). This may in part reflect an increased number of targetable events in recurrent or refractory pediatric cancers. Correlative studies analyzing pre-treatment tumors from MATCH study patients are underway and will address this hypothesis. Prior history of molecular testing was associated with higher match and enrollment rate and poor clinical status was a common reason for not enrolling on a treatment protocol, suggesting that early molecular screening of children with solid malignancies may facilitate enrollment to biomarker-selected trials of targeted therapies. Clinical trial information: NCT03155620.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.10007
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 6
    Online Resource
    Online Resource
    Validation and genomic interrogation of the MET variant rs11762213 as a predictor of adverse outcomes in clear cell renal cell carcinoma.
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 4_suppl ( 2014-02-01), p. 395-395
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 4_suppl ( 2014-02-01), p. 395-395
    Abstract: 395 Background: The exonic single nucleotide variant rs11762213 located in the METoncogene has recently been identified as a prognostic marker in clear cell renal cell carcinoma (ccRCC) (Schutz et al, Lancet Oncol 2013). We sought to validate this finding and explore the biologic implications using The Cancer Genome Atlas (TCGA) cohort. Methods: The variant call file (VCF) and expression data was available for 272 patients. We then extracted the data for rs11762213 as follows for the "normal" sample: allelic fraction for variant allele 〉 80% is homozygous variant while allelic fraction for variant allele 30% to 70% is heterozygous. Paired tumor-normal materials, genomic data (whole exome, RNAseq, and DNA methylation) and clinical information were acquired from publically available TCGA datasets. Kaplan-Meier method was used to estimate the survival probabilities. Cancer specific survival (CSS) was analyzed using the competing risk method and Cox proportional hazard regression was used for analysis of time to recurrence. Multivariate competing risk models were also fitted in the TCGA cohort in order to adjust for the Mayo Clinic SSIGN score. Results: Overall, the variant allele of rs11762213 was detected in 10.3% of the cohort and was associated with higher nuclear grade (p=0.03) and trended toward higher clinical stage (p=0.07). After adjusting for the prognostic SSIGN score, the risk allele remained a significant predictor for adverse cancer specific survival (CSS; p 〈 0.0001; Odds Ratio [OR] 3.88, 95% confidence interval [CI] 1.99-7.56) and time to recurrence (TTR; p=0.003; OR 2.97; 95% CI 1.44-6.2). RNA sequencing data for MET did not reveal differences in tumor mRNA expression when stratified by risk allele, but did show differences in the normal kidney expression (p=0.02) in a smaller cohort (n=61). Conclusions: The exonic MET variant rs11762213 is an independent predictor of adverse CSS and TTR in ccRCC and could be integrated into clinical practice for prognostic stratification. Gene expression analysis suggests that inherited variation at MET influences expression of the gene in normal kidney tissue. Further external validation and biological interrogation is necessary.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2014.32.4_suppl.395
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
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  • 7
    Online Resource
    Online Resource
    Long-Term Outcomes and Retreatment Among Patients With Previously Treated, Programmed Death-Ligand 1‒Positive, Advanced Non‒Small-Cell Lung Cancer in the KEYNOTE-010 Study
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 14 ( 2020-05-10), p. 1580-1590
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 14 ( 2020-05-10), p. 1580-1590
    Abstract: In the KEYNOTE-010 study, pembrolizumab improved overall survival (OS) versus docetaxel in previously treated, programmed death-ligand 1 (PD-L1)‒expressing advanced non‒small-cell lung cancer (NSCLC) in patients with a tumor proportion score (TPS) ≥ 50% and ≥ 1%. We report KEYNOTE-010 long-term outcomes, including after 35 cycles/2 years or second-course pembrolizumab. METHODS Of 1,033 patients randomly assigned (intention to treat), 690 received up to 35 cycles/2 years of pembrolizumab 2 mg/kg (n = 344) or 10 mg/kg (n = 346) every 3 weeks, and 343 received docetaxel 75 mg/m 2 every 3 weeks. Eligible patients with disease progression after 35 cycles/2 years of pembrolizumab could receive second-course treatment (up to 17 cycles). Pembrolizumab doses were pooled because no between-dose difference was observed at primary analysis. RESULTS Pembrolizumab continued to improve OS over docetaxel in the PD-L1 TPS ≥ 50% and ≥ 1% groups (hazard ratio [HR], 0.53; 95% CI, 0.42 to 0.66; P 〈 .00001; and HR, 0.69; 95% CI, 0.60 to 0.80; P 〈 .00001, respectively) after a 42.6-month (range, 35.2-53.2 months) median follow-up. Estimated 36-month OS rates were 34.5% versus 12.7% and 22.9% versus 11.0%, respectively. Grade 3-5 treatment-related adverse events occurred in 16% versus 37% of patients, respectively. Seventy-nine of 690 patients completed 35 cycles/2 years of pembrolizumab; 12-month OS and progression-free survival rates after completing treatment were 98.7% (95% CI, 91.1% to 99.8%) and 72.5% (95% CI, 59.9% to 81.8%), respectively. Seventy-five patients (95%) had objective response (RECIST v1.1, blinded independent central review) and 48 (64%) had ongoing response. Grade 3-5 treatment-related adverse events occurred in 17.7% of patients. Fourteen patients received second-course pembrolizumab: 5 completed 17 cycles, 6 (43%) had partial response, and 5 (36%) had stable disease. CONCLUSION Pembrolizumab provided long-term OS benefit over docetaxel, with manageable safety, durable responses among patients receiving 2 years of treatment, and disease control with second-course treatment, further supporting pembrolizumab for previously treated, PD-L1‒expressing advanced NSCLC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.19.02446
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 8
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    Adjuvant chemotherapy and radiation therapy (RT) versus RT alone for women with high-risk endometrial cancer: Toxicity and quality-of-life results of the randomized PORTEC-3 trial.
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 15_suppl ( 2015-05-20), p. 5501-5501
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 15_suppl ( 2015-05-20), p. 5501-5501
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2015.33.15_suppl.5501
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
    detail.hit.zdb_id: 2005181-5
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  • 9
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    Patient reported outcomes (PROs) of multiple myeloma (MM) patients treated with panobinostat (PAN) after ≥2 lines of therapy based on the international phase 3, randomized, double-blind, placebo-controlled, PANORAMA-1 trial.
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 15_suppl ( 2016-05-20), p. 8054-8054
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. 8054-8054
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2016.34.15_suppl.8054
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
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  • 10
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    Phase 1B/2A safety, pharmacokinetics, and pharmacodynamics study of fosciclopirox alone and in combination with cytarabine in patients with relapsed/refractory acute myeloid leukemia.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. TPS7069-TPS7069
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. TPS7069-TPS7069
    Abstract: TPS7069 Background: Fosciclopirox (F) is a γ-secretase inhibitor being developed for the treatment of acute myeloid leukemia (AML). Following intravenous (IV) administration, F is rapidly and completely metabolized to its active metabolite, ciclopirox (CPX). CPX binds to γ-secretase complex proteins Presenilin 1 and Nicastrin, which are essential for Notch activation. In HL60 cells, CPX inhibits Notch 1 and Notch 2 expression, reduces levels of γ-secretase complex proteins Presenilin 1 and Nicastrin, and decreases expression of the downstream Notch target gene Hes-1. Utilizing Notable Labs predictive precision medicine platform, bone marrow (BM) and peripheral blood (PB) samples obtained from 10 AML patients treated with CPX demonstrated significant blast count reductions. Methods: Study CPX-POM-003 (NCT04956042) is an open-label Phase 1B/2A, trial designed to characterize the efficacy, safety, and PK/PD of F alone and in combination with cytarabine (ara-C) in patients with relapsed/refractory AML (R/R AML). Eligible patients must be 18 years of age or older with relapsed AML after complete remission or with primary refractory AML refractory to at least two cycles of induction therapy. There will be up to three cohorts of patients, approximately 42 R/R AML patients, evaluated. If disease response to F alone (Cohort 1a) is observed in at least 4 of 14 patients, an additional 14 patients will be enrolled in Cohort 1b. If disease response is not observed following F alone, the study may be terminated or a second cohort, Cohort 2a, may be initiated to evaluate the combination of F + ara-C. If disease response to F + ara-C is observed in at least 4 of 14 patients, an additional 14 patients will be enrolled in Cohort 2b. If response to F + ara-C is not observed in at least 4 of 14 patients, the study will be stopped for futility. F is being administered as 900 mg/m 2 once daily as a 20-minute IV infusion on Days 1 to 5 of each 21-day treatment cycle. Ara-C is administered as 1 gm/m 2 once daily on Days 1 to 5 of each cycle. BM and PB samples are collected prior to and during Cycles 1 (C1) and 2 (C2) for disease response assessment and blast count determination. Additional BM and PB samples are obtained after every two cycles beyond C2 for patients continuing treatment. Disease response is determined based on Döhner et al, Blood 2017;129(4)424-447. Next Generation Sequencing (NGS) profiles will be determined prior to and at the end of C1, and thereafter as clinically indicated. Immunohistochemistry will be performed on BM samples to elucidate drug mechanism. Ex vivo Drug Sensitivity Screening (DSS) will be performed on BM and PB samples obtained prior to treatment as well as on C1 Days 8 and 21. The steady-state plasma pharmacokinetics of F are being characterized during C1. Enrollment began in October 2022 with four patients enrolled to date. Clinical trial information: NCT04956042.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.TPS7069
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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