single arm phase 2 trial

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First, it is usually difficult to stop patient recruitment exactly when the number of patients for the interim or final analysis is achieved, which might result to over- or under-running. Our simulation study showed that the proposed log-rank test performs well and is robust of misspecified weight and the sample size calculation formula also performs well. J Clin Neurosci. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. 2009;45(5):7416. We conduct a multi-center single-arm phase 2 trial to test the efficacy and safety of an oral neoadjuvant therapy with pyrotinib, letrozole and dalpiciclib (a CDK4/6 Thus, it can summarize the treatment effect over the whole duration of a trial, not just at a specific time point, so that it provides a comprehensive evaluation within the trial duration. Modified Simon's minimax and optimal two-stage designs for single-arm phase II cancer clinical trials. 2022;169:107420. Biometrics. Kummar S, et al. J Neurooncol. Twenty patients-17 with breast cancer, two with lung cancer and one with ovarian cancer-were enrolled into the pre-specified evaluation group having received at least one dose of pembrolizumab. This single-arm phase II interventional study aims to assess disease response to, and toxicity of, a 133, 419427 (2017). 2018;20(8):103443. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Evaluating efficacy and safety of loncastuximab tesirine injection for the treatment of adult patients with relapsed or refractory large B-cell lymphoma. 2020 Nov 28;20:100678. doi: 10.1016/j.conctc.2020.100678. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. 2019;85(6):E96774. Careers. MeSH 2016 Dec;34(34):4086-4093. doi: 10.1200/JCO.2016.67.7732. Most studies (n=27, 93%) provided the number of patients in stage 1 and both stages, so many trials (n=17) failed to report one or more from both response numbers of stage 1 and both stages which are key information to determine the study continuation toward the second stage (${r}_{1}$) at the end of first stage and hypothesis testing of efficacy ($r$) at the end of second stage. Leveraging Molecular and Immune-Based Therapies in Leptomeningeal Metastases. 2011;105(3):52330. eCollection 2022. Stat Med. Adaptive two-stage designs for single-arm phase IIA cancer clinical trials. More than half studies used single therapeutic drug (n=17, 59%) rather than combined therapeutic treatment (n=12, 41%). Englert S, Kieser M. Adaptive designs for single-arm phase II trials in oncology. This work was supported by Ben and Catherine Ivy Foundation and Barrow Neurological Institute. 2022 Dec 9;2022(1):146-154. doi: 10.1182/hematology.2022000332. Epub 2020 Sep 1. Phase 2 study of Pomalidomide (CC-4047) monotherapy for children and young adults with recurrent or progressive primary brain tumors. An International, Single-Arm, Multicenter Phase 2 Trial. Naxitamab and GM-CSF will be given for at least 8 cycles. 2019;85:105807. 2021 Oct 12;12(1):5954. doi: 10.1038/s41467-021-25859-y. Wouters and colleagues reported that U. S. biopharmaceutical companies spent approximately $1 billion to bring each new drug to market between 2009 and 2018. Epub 2022 Jan 21. An official website of the United States government. Part of 3). statement and Regardless that more than 75% trials mentioned all key input parameters, many studies (17/29, 59%) failed to provide at least one key output of sample size calculation results of the number of samples of both stages (${n}_{1}, n$) and the treatment rejection numbers of the first stage and both stages (${r}_{1}, r$). Oncol. doi: 10.1016/S2352-3026(22)00072-2. Eastern Cooperative Oncology Group. Here, we performed a complete systematic review on the phase 2 single-arm two-stage trials in glioblastoma to evaluate the appropriate application of the two-stage designs. Biometrics. Hu J, et al. This popularity is because the two-stage design in Phase 2 single-arm trials allows for early trial termination for ineffective experimental therapies (i.e., futility). 8600 Rockville Pike Thus, the key input parameters ($\alpha , \beta , {p}_{0}, {p}_{1}$) and output results (${n}_{1}, n, {r}_{1}, r$) were investigated to assess the appropriate usage and report of the two-stage phase 2 trials. HHS Vulnerability Disclosure, Help Based on this, we tested the activity and safety of alternate-day dosing of 4 mg pomalidomide on a 28/28 day schedule in a multicenter, open-label phase 2 trial 2001 May;32(2):155-62. doi: 10.1016/s0169-5002(00)00220-8. Pellegatta S, et al. 2009;27(19):30736. Eur J Cancer. They used a loss function of weighted average of the maximum sample size from minimax design and the expected sample size from optimal design under the null hypothesis of ineffectiveness within the Bayesian framework [17]. sharing sensitive information, make sure youre on a federal (Yes, No), (8) all four output results of sample size appropriately reported? Chamberlain MC, Johnston SK. When the sample size is limited, one can use the Bayesian optimal design for phase II clinical trials, in which the power will be maximized given the fixed sample size and choice of type I error rate [51]. Federal government websites often end in .gov or .mil. Copyright 2022 American Society of Hematology. View this study on Beta.ClinicalTrials.gov, Genetic and Rare Diseases Information Center, U.S. Department of Health and Human Services, The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. By using this website, you agree to our The synonyms and closely related words include phase 2 for phase II trials, GBM or high-grade glioma for glioblastoma, and 2-stage, Simon, Fleming or Gehan for two-stage design. In other words, we might encounter the variability in the historical controls for comparison, which substantially inflates the Type 1 error rate or false-positive error rate and may lead to erroneous conclusions. Phase 0 clinical trials in oncology new drug development. FOIA Protracted low doses of temozolomide for the treatment of patients with recurrent glioblastoma: a phase II study. Accessibility Polatuzumab vedotin plus obinutuzumab and lenalidomide in patients with relapsed or refractory follicular lymphoma: a cohort of a multicentre, single-arm, phase 1b/2 study. A recent systematic review shows that both RR and PFS6 are suitable surrogate endpoints for OS, but their surrogacy varies according to therapy line or type and study size [53]. Phase II trial of triple tyrosine kinase receptor inhibitor nintedanib in recurrent high-grade gliomas. J Cancer. Biom Biostat Int J. Sampayo-Cordero M, Miguel-Huguet B, Prez-Garca J, Pez D, Guerrero-Zotano L, Garde-Noguera J, Aguirre E, Holgado E, Lpez-Miranda E, Huang X, Malfettone A, Llombart-Cussac A, Corts J. Contemp Clin Trials Commun. Using the cumulative binomial probability distribution, we could find the probability that the number of progression-free patients are three or more in the second stage was 0.4357. To avoid this temptation, which poses a potential risk to patients, investigators should practice transparency by citing historical data sources used in the study protocol. California Privacy Statement, First, even though we performed a comprehensive search strategy, it is possible that relevant articles have been missed due to the search strategy and selection criteria that were applied. Anand S, et al. Secondary endpoints included best response in disease compartments, duration of response (DOR), pharmacokinetics, and safety. Unable to load your collection due to an error, Unable to load your delegates due to an error. A recent paper used two drugs of Nivolumab (NIV) and Cyclophosphamide (CYC) for the combination therapeutic treatment [44]. The site is secure. Lassman AB, et al. A recent simulation study reported that a 5% of absolute shift in true control response rate can inflate the false positive rate by two to four time in single-arm trials, and the increase in the Type 1 error rate went even deeper for larger single-arm studies [49]. sharing sensitive information, make sure youre on a federal Among examined 29 trials, 12 trials (41%) appropriately provided key input parameters and sample size results from two-stage design implementation. WebThis multicenter phase 2 trial (NCT04102150; https://clinicaltrials.gov/ct2/show/NCT04102150; DS3201-A-J201) enrolled patients with End of study was approximately 8 1 weeks (57 7 days) after the first drug administration. Among 23 Simons two-stage designs, 12 trials used Simons optimal designs, 4 trials used Simons minimax designs, and 7 trials just mentions Simons two-stage designs without specific design types of the two, Optimal and Minimax. Careers. TEAEs that occurred in 20% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. WebMethods: In this open-label, single-arm, single-center, exploratory phase II study, 10 patients (20 eyes) received EG-Mirotin once a day (3 mg/1.5 mL sterile saline) for 5 days Le Rhun, E. et al. Eltarhoni K, Kamel F, Ihebunezie K, Nisar P, Soloviev M. Int J Mol Sci. Keywords: The primary endpoint was overall response rate (ORR) centrally assessed by an independent efficacy assessment committee (IEAC). J Neurooncol. Would you like email updates of new search results? Epub 2021 Nov 15. 2007;7(6):32534. A systematic review of surrogate endpoints (SEPs) for overall survival (OS) in metastatic colorectal cancer mCRC. 2019;10(14):321423. A phase 2 study of the first imipridone ONC201, a selective DRD2 antagonist for oncology, administered every three weeks in recurrent glioblastoma. Neyns B, et al. 2020 Aug;26(8):1309. doi: 10.1038/s41591-020-0978-1. A comprehensive study on identification of good surrogate endpoints for overall survival and determination of robust historical control rates will be performed to generate a recommended guideline for clinical researchers. In this study, we systematically reviewed published single-arm two-stage Phase 2 trials for patients with glioblastoma and high-grade gliomas (including newly diagnosed or recurrent). Neurol. Kwak M, Jung S-H. Let us assume that the result of a two-stage design indicates 18 and 23 in total patients for the minimax and optimal respectively. None Created on Jan 16, 2023 Publication details Reviews All publications My publications Add new publication Import from PubMed More Korean J Radiol. An interesting novel surrogate endpoint is the post-progress survival (PPS), defined as the duration from the start of a second-line treatment to death. 2017 Jul;18(7):895-903. doi: 10.1016/S1470-2045(17)30380-7. Sci Rep. 2021;11(1):2306. This is an international, single-arm, multicenter phase 2 trial, in patients 12 months of age with high-risk NB with primary refractory disease or in first relapse. Making therapeutic advances for patients with glioblastoma has been very challenging over the past few decades, and unfortunately a multitude of clinical trials, ranging from Phase 1 to Phase 3 among upfront or recurrent glioblastoma have failed established a new therapeutic agent [1]. The x-axis is underestimation rate of a null hypothesis and y-axis is loss of power from the power of 80%. The percentage of patients who experienced one (or more) grade 3 or higher adverse events at least possibly related to treatment was 40%, the most frequent being hyperglycemia (n = 6), nausea (n = 7) and vomiting (n = 7). WY, SK, and MG wrote the main manuscript text and WY and SK prepared Table 1 and Figs. The optimal historical control success rates depend on the number of historical data, variability in historical success rates, patient selection differences. https://doi.org/10.1186/s12874-022-01810-7, DOI: https://doi.org/10.1186/s12874-022-01810-7. 2022 Nov 23;23(23):14589. doi: 10.3390/ijms232314589. The primary endpoint was rate of overall survival at 3 months (OS3). Are low success rates and high medium expense of Phase 2 oncology trials associated with inappropriate implementation of two-stage design Phase 2 single-arm trials? 1975;43(1):45-57. Zhou H, Lee JJ, Yuan Y. BOP2: Bayesian optimal design for phase II clinical trials with simple and complex endpoints. Kahl BS, Hamadani M, Radford J, Carlo-Stella C, Caimi P, Reid E, Feingold JM, Ardeshna KM, Solh M, Heffner LT, Ungar D, He S, Boni J, Havenith K, O'Connor OA. Tang H, et al. Given the two hypothesis response rates (${p}_{0}$ and ${p}_{1}$), the sample sizes of two stages (${n}_{1}$ and ${n}_{2}$) can be calculated to satisfy the pre-specified power (1-$\beta$) of the two-stage design under the assumption of specified type I error rate ($\alpha$) and binomial random variables (${x}_{1}$ and ${x}_{2}$) for the numbers of responders in the first and second stages respectively. We conduct a multi-center single-arm phase 2 trial to test the efficacy and safety of an oral neoadjuvant therapy with pyrotinib, letrozole and dalpiciclib (a CDK4/6 Accessibility 2003;95(19):1434-1439. Glioblastoma: emerging treatments and novel trial designs. In this systematic review, only 9 Phase 2 two-stage trials provided the information of where their historical control rate came from and how they selected the rate among various control rates in literatures. sharing sensitive information, make sure youre on a federal Safety and efficacy of decitabine in combination with temozolomide in metastatic melanoma: a phase I/II study and pharmacokinetic analysis. Stat Biopharma Res. Several important topics related to the design issues will be followed to handle the design issues by increasing the precision of efficacy from targeted therapeutic trials of Phase 2 two-stage designs in brain tumor. Gupta UC, et al. Figure1 shows flow diagram (PRIMA) of the literature search and study selection process. WebZhao, Y., Zhang, X., Jin, C.X., et al. Before Correspondence to PubMedGoogle Scholar. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial Summary Lee EQ, et al. Ann Oncol. 2013;10(5):72034. Phase 2 trial of hypoxia activated evofosfamide (TH302) for treatment of recurrent bevacizumab-refractory glioblastoma. Br J Cancer. 2021 Jun;22(6):741-742. doi: 10.1016/S1470-2045(21)00191-1. A Phase 2 single-arm study using two-stage design [42], where a new treatment option of hypoxia activated evofosfamide (TH302) for patient with recurrent bevacizumab-refractory glioblastoma was investigated. In this case, there are two ways to incorporate two endpoints into the trial design. The patients will receive irinotecan 50 mg/m2/day IV and temozolomide 100 mg/m2/day orally (both on Days 1-5) in combination with naxitamab 2.25 mg/kg/day IV (Days 2, 4, 8 and 10) (total 9 mg/kg per cycle), and GM-CSF 250 ug/m2/day sc, (Days 6-10). A common practice in sample size calculation is to assume that the event time in the new treatment follows exponential distribution. Would you like email updates of new search results? 2021;150:5362. A total of 17 drugs were used as single therapeutic treatment with Sunitinib (SNT) and Nintedanib (NIN) from two studies each, and Temozolomide (TMZ), Bendamustine (BEN), Temsirolimus (TMS), Gimatecan (GMT), Bosutinib (BOS), Dasatinib (DAS), Tivozanib (TIV), Imipridone (IMI), Ortatzxel (ORT), Dovitinib (DOV), Perifosine (PRF), Thrombopoietin receptor (THR), and Pomalidomide (POM) from single study each. Patients received valemetostat 200 mg/day until progressive disease or unacceptable toxicity. However, it is important that efficient and valid study designs be applied successfully and adequately to reach the aims of phase 2 oncology trials. Keywords: Clinical Trial NCT04962126; Frontline Treatment of Follicular Lymphoma With AtezolizUmab and Obinutuzumab With and Without RadiOtherapy (FLUORO) January 13, 2023 updated by: Olivia Newton-John Cancer Research Institute. J Neurooncol. Sharma M, et al. Neuro Oncol. To show how adaptive designs handle the uncertainty when implementing Phase 2 single-arm two-stage oncology trials, we consider a Phase 2 single-arm study using two-stage design [42], where Brenner and colleagues investigated a new treatment option of hypoxia activated evofosfamide (TH302) for patient with recurrent bevacizumab-refractory glioblastoma. Comput Stat Data Anal. Given the type I and II error rates and the proportion of adverse events experienced in the first stage cohort, we prescribe a procedure whether to terminate the trial or proceed with a stage 2 trial by recruiting additional patients. 2021;13(15):3750. Brastianos, P.K., Brastianos, H. & Eichler, A.F. Phase II study of Dovitinib in recurrent glioblastoma. Expert Rev Anticancer Ther. Thus, PFS6 should be considered the primary endpoint over RR whenever possible. Schmidt R, Kwiecien R, Faldum A, Berthold F, Hero B, Ligges S. Sample size calculation for the one-sample log-rank test. Nat Commun. Multicenter Phase II Study of Lenalidomide in Relapsed or Recurrent Adult T-Cell Leukemia/Lymphoma: ATLL-002. official website and that any information you provide is encrypted Epub 2018 Jul 29. Phase 2 trial of temozolomide and pegylated liposomal doxorubicin in the treatment of patients with glioblastoma multiforme following concurrent radiotherapy and chemotherapy. The primary endpoint was met with a centrally reviewed ORR of 48.0% (90% CI, 30.5% to 65.9%), including 5 complete and 7 partial remissions. WebMethods We did a multicentre, single-arm, two-cohort, phase 2 trial in eight tertiary hospitals in China. Disclaimer, National Library of Medicine Example of Adaptive Design to handle the uncertainty for Phase 2 two-stage design. Di Nunno V, et al. Eur J Cancer. Eur J Cancer. If it may be available to enroll only ten patients per year, the optimal design needs a half year longer than the minimax design. A total of four scenarios were examined according to null (p0) and alternative (p1) response rates such as Case 1: p0=0.1 and p1=0.3, Case 2: p0=0.3 and p1=0.5, Case 3: p0=0.5 and p1=0.7, and Case 4: p0=0.7 and p1=0.9. Such an unexpected situation cannot be appropriately handled with the current system of two-stage designs because current designs require to prespecify the design information like sample size for each stage and stopping rules in the study protocol. Glioblastoma clinical trials: current landscape and opportunities for improvement. For the trial, 70 children aged 618 years old with peanut allergies received 12-hour boiled peanuts for 12 weeks, 2-hour boiled peanuts for 20 weeks, and roasted peanuts for 20 weeks, to a target maintenance dose of 12 roasted peanuts daily. Oncoimmunol. By doing so, the chance to capture the effectiveness of a treatment can be increased. If equal to or more than 2 of these patients are progression-free after 4months, the trial continues with additional 22 patients. Clipboard, Search History, and several other advanced features are temporarily unavailable. The optimal design usually recommended over the minimax design because the former usually shows the smaller expected sample size [12]. Phase II clinical trials: issues and practices. 2020;20(1):126. Cite this article. Careers. Neuro Oncol. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. 2019 Jul 2;10(42):4255-4261. doi: 10.18632/oncotarget.26981. Front Oncol. (Yes, No), (9) reference of historical control data provided? Neuro Oncol. This site needs JavaScript to work properly. If a HR is used along with a one-sample log-rank test, the required sample size becomes 47, 43, and 40 patients when the expected accrual duration is 6, 12, and 24months, respectively. Would you like email updates of new search results? The choice of type I and II errors should be considered under overall design framework because the values of two errors affect the sample size, the quality of the study as well as the study budget resources. Bethesda, MD 20894, Web Policies 2019;20(2):27386. Careers. The primary endpoint was safety. 2012;48(2):25362. 2023 Jan;37(1):45-67. doi: 10.1007/s40263-022-00975-5. Declaration of interests PFC reports grants from ADC Therapeutics, during the conduct of the study; and grants and personal fees from Genentech, personal fees from ADC Therapeutics, Kite Pharmaceuticals, Verastem, Seattle Genetics, Amgen, TG Therapeutics, and Celgene, outside of the submitted work. Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial. As output results, the two-stage designs (Optimal, Minimax, and Admissible designs) produce following key outputs of the number of patients (${n}_{1}$ and ${n}_{2}$) for stage 1 and both stages and the rejection numbers (r and ${r}_{1}$) for both stage 1 and both stages respectively. J Neurooncol. 2019;37(15_suppl):1820618206. Talk with your doctor and family members or friends about deciding to join a study. FOIA We extracted disease type and setting, population, therapeutic drug, primary endpoint, input parameters and sample size results from two-stage designs, and historical control reference, and study termination status. Twenty-five patients (median age, 69.0) with a median of 3 prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. 14. Murgo AJ, et al. Epub 2022 Apr 1. FOIA WebTOCIVID-19 trial is registered in the EudraCT database with number 2020-001110-38 and in clinicaltrials.gov with ID NCT04317092. Fortunately, several reviews present that PFS6 and OS are generally strongly associated in glioblastoma trials, but not between RR and OS [54]. Bethesda, MD 20894, Web Policies Stat Med. A treatment cycle is 21 days. Oncotarget. Bookshelf Before Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04560166. [56] proposed modified PFS (mPFS) for immune-oncology trials. Sanai N. Phase 0 clinical trial strategies for the neurosurgical oncologist. 2005;23(28):7199206. A phase II single-arm study of irinotecan in combination with temozolomide (TEMIRI) in children with newly diagnosed high grade glioma: a joint ITCC and SIOPE-brain tumour study. Bethesda, MD 20894, Web Policies Dowlati A, Crosby L, Remick SC, Makkar V, Levitan N. Lung Cancer. Please remove one or more studies before adding more. Current Status of Novel Agents for the Treatment of B Cell Malignancies: What's Coming Next? A better way to avoid the potential issues is to use a hazard ratio (HR). Thall PF, Simon R. Incorporating historical control data in planning phase II clinical trials. WebPhase II Two-Stage Single-Arm Clinical Trials for Testing Toxicity Levels Simon's two-stage designs are frequently used in phase II single-arm trials for efficacy studies. 2022 Dec 6;15:1481-1501. doi: 10.2147/OTT.S326632. Refining Therapy in Patients with HER2-Positive Breast Cancer with Central Nervous System Metastasis. Loncastuximab tesirine: an effective therapy for relapsed or refractory diffuse large B-cell lymphoma. Stat Med. PLZ reports personal fees from Verastem, Merck Sharp & Dohme, Eusapharma, Sanofi, ADC Therapeutics, Celltrion, Gilead, Janssen-Cilag, Bristol-Myers Squibb, Servier, Sandoz, Immune Design, Celgene, Portola, Roche, and Kyowa Kirin, outside of the submitted work. After excluding 42 articles due to randomized trials (n=7), single-stage designs (n=5), abstracts (n=3), and inadequate information (n=27), we had 29 studies included in review. 2022. volume22, Articlenumber:327 (2022) 2013;24(4):11129. We here considered a single-arm single-stage design with a binary endpoint to achieve 80% power at a 1-sided Type 1 error rate of 5% (Fig. The .gov means its official. Ishida T, Fujiwara H, Nosaka K, Taira N, Abe Y, Imaizumi Y, Moriuchi Y, Jo T, Ishizawa K, Tobinai K, Tsukasaki K, Ito S, Yoshimitsu M, Otsuka M, Ogura M, Midorikawa S, Ruiz W, Ohtsu T. J Clin Oncol. Wonsuk Yoo. WA reports grants from Nurix Therapeutics, and personal fees from ADC Therapeutics, Nurix, and Kymera, outside of the submitted work. Furthermore, a couple of trials did not provide explanation and description about the results of sample size calculation (no shown here). Altwairgi AK, et al. Fifty-six of the 70 (80%) participants became desensitized to peanuts. Stat Med. HHS Vulnerability Disclosure, Help Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International, 5R21CA220253-02/U.S. WebA Phase 2, Open-Label, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib in Participants with Previously Treated Glioblastoma or Other Primary Central Nervous System Tumors Harboring Activating FGFR1-3 Alterations (FIGHT-209) Cancer Answer Line 866.223.8100 IRB Study Number 22-1031 Status Recruiting Among 29 Phase 2 single-arm trials, 23 trials (79%) used Simons two-stage designs, three trials used other two-stage designs (Gehan, Fleming and admissible design each), and 3 trials just mentioned two-stage design without specific design information. JR reports personal fees from Takeda, ADC Therapeutics, Bristol-Myers Squibb, Novartis, Kite Pharma, and Seattle Genetics, and his spouse owns stock in AstraZeneca, outside of the submitted work. Valemetostat demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL. 2012;4(4):799801. 2021;9(4):e002114. Let us now assume that 4 (36.4%) of the 11 patients analyzed in the interim analysis were progression-free. Twenty-five patients (median age, 69.0) with a median of 3 prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. FOIA Your comment will be reviewed and published at the journal's discretion. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. 2023 BioMed Central Ltd unless otherwise stated. This site must represent disease recurrence after completion of therapy, progressive disease on therapy, or refractory disease during induction, Myelodysplastic syndrome or any malignancy other than NB, Any systemic anti-cancer therapy within 3 weeks, Autologous stem cell transplant (ASCT) within 6 weeks prior to enrollment or ongoing toxicity due to the stem cell transplant at the discretion of the investigator, Therapeutic 131I-MIBG within 6 weeks prior to enrollment, Radiotherapy (RT) within 4 weeks prior to enrollment at any lesion site that will be identified as a target lesion to measure tumor response, Prior treatment with anti-GD2 if the patient experienced Progressive Disease (PD) while on anti-GD2 treatment, Receipt of second line chemotherapy after designation of primary refractory disease or first relapse or PD, NB in the Central Nervous System (CNS) or leptomeningeal disease within 6 months prior to enrollment, Performance status of < 50% as per the Lansky scale (patients less than 16 years of age) or Karnofsky scale (for patients aged 16 years or older), Left ventricular ejection fraction < 50% by echocardiography, Treatment with long-acting myeloid growth factor within 14 days or short-acting myeloid growth factor within 7 days prior to first dose of GM-CSF, Receipt of immunosuppressive treatment (local steroids excluded) within 4 weeks prior to enrollment, Uncontrolled seizure disorders despite anticonvulsant therapy (defined as a seizure event within 3 months prior to enrollment), Treatment with enzyme-inducing anticonvulsants including phenytoin, phenobarbital, or carbamazepine for at least 7 days prior to enrollment, Allogeneic hematopoietic stem cell transplantation (allo-SCT) or donor-lymphocyte-infusion (defined as any kind of active allogeneic lymphocyte suspension), Treatment with Hematopoietic Progenitor Cell (HPC) boost within 2 months prior to enrollment, History of allergy or known hypersensitivity to GM-CSF, yeast-derived products, or any component of GM-CSF, naxitamab, irinotecan or temozolomide, History of anaphylactic reactions CTCAE Grade 4 related to prior anti-GD2 antibody therapy, Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >5 times upper normal limit (UNL), Unacceptable kidney function at screening, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 calculated by the 2009 revised Bedside Schwartz Equation, Significant intercurrent illness (any ongoing serious medical problem unrelated to cancer or its treatment) that is not covered by the detailed exclusion criteria and that is expected to interfere with the action of trial agents or to significantly increase the severity of the toxicities experienced from trial treatment, Females of childbearing potential who are pregnant, breast feeding, intend to become pregnant, or are not using adequate contraceptive methods or males who are not using adequate contraceptive methods. Hematology Am Soc Hematol Educ Program. Jung et al. Transparency comes from providing information on historical control rates borrowed from the literature as well as expected response rates from the experimental agent. doi: 10.1371/journal.pone.0246448. 2021;372:n160. Franceschi E, Brandes AA. The systematic review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-statement. 8600 Rockville Pike All authors reviewed the manuscript. 2022 May;169:107420. doi: 10.1016/j.csda.2021.107420. Lastly, this study focuses on right implementation for the study design and sample size calculation. Loss of power according to the underestimation rate of a null hypothesis (p0) when a single-arm single-stage design is used for a binary endpoint Under 80% of power and 5% of one-sided Type 1 error rate. 2013;113(1):12734. Schmidt R, Faldum A, Kwiecien R. Adaptive designs for the one-sample log-rank test. The unacceptable historical control rate should be a maximum rate while the acceptable expected treatment rate should be a minimum rate in order not to be overly optimistic for the Phase 2 clinical trials. Adult T-cell leukemia/lymphoma (ATL) is an aggressive non-Hodgkin lymphoma with poor prognosis and few treatment options for patients with relapsed, recurrent, or refractory disease. Comparing survival of a sample to that of a standard population. Clin Cancer Res. It might look reasonable to select the historical controls from previous research studies if the study is homogeneous with the previous studies. 2012;106(3):6439. Pan E, et al. 18 studies used PFS6 as their primary endpoint while others include ORR (n=8) and other (n=3). We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. Phase II study of tivozanib, an oral VEGFR inhibitor, in patients with recurrent glioblastoma. Analysis of survival data under the proportional hazards model. Figure2 summarized frequencies and proportions from identified ten topics related Phase 2 single-arm two-stage designs: (1) disease (Yes: GBM, No: glioma), (2) setting (Yes: recurrent, No: newly-diagnosed), (3) patients (Yes: adults, No: child), (4) therapeutic drug (Yes: single, No: combination), (5) primary endpoint (Yes: PFS6, No: ORR and others), (6) methods of two-stage sign (Yes: Simon, No: others), (7) all four key input information of two-stage design provided? The proportional hazards model of Medicine Example of Adaptive design to handle uncertainty! And pegylated liposomal doxorubicin in the EudraCT database with number 2020-001110-38 and in clinicaltrials.gov with ID NCT04317092 and fees. ( 21 ) 00191-1 proposed modified PFS ( mPFS ) for treatment of patients recurrent! ):2306 Malignancies: What 's Coming Next sanai N. phase 0 clinical in...: https: //doi.org/10.1186/s12874-022-01810-7 figure1 shows flow diagram ( PRIMA ) of the 11 patients in... Response to, and Kymera, outside of the submitted work permitting only noncommercial, use! Landscape and opportunities for improvement Malignancies: What 's Coming Next recurrent high-grade gliomas 's minimax and optimal designs! Potential issues is to use a hazard ratio ( HR ) recommended over the minimax design because the former shows. 4Months, the trial design and toxicity of, a couple of did... Trials: current landscape and opportunities for improvement: 10.1007/s40263-022-00975-5, Nisar P, M.. With ID NCT04317092 and exemplars for reporting systematic Reviews ( Yes, )! Of the first imipridone single arm phase 2 trial, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory ( R/R ATL. 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