Quantitative Checklist for Autism in Toddlers (Q-CHAT). A population screening study with follow-up: the case for multiple time-point screening for autism

ObjectiveThis is a prospective population screening study for autism in toddlers aged 18–30 months old using the Quantitative Checklist for Autism in Toddlers (Q-CHAT), with follow-up at age 4.DesignObservational study.SettingLuton, Bedfordshire and Cambridgeshire in the UK.Participants13 070 toddlers registered on the Child Health Surveillance Database between March 2008 and April 2009, with follow-up at age 4; 3770 (29%) were screened for autism at 18–30 months using the Q-CHAT and the Childhood Autism Spectrum Test (CAST) at follow-up at age 4.InterventionsA stratified sample across the Q-CHAT score distribution was invited for diagnostic assessment (phase 1). The 4-year follow-up included the CAST and the Checklist for Referral (CFR). All with CAST ≥15, phase 1 diagnostic assessment or with developmental concerns on the CFR were invited for diagnostic assessment (phase 2). Standardised diagnostic assessment at both time-points was conducted to establish the test accuracy of the Q-CHAT.Main outcome measuresConsensus diagnostic outcome at phase 1 and phase 2.ResultsAt phase 1, 3770 Q-CHATs were returned (29% response) and 121 undertook diagnostic assessment, of whom 11 met the criteria for autism. All 11 screened positive on the Q-CHAT. The positive predictive value (PPV) at a cut-point of 39 was 17% (95% CI 8% to 31%). At phase 2, 2005 of 3472 CASTs and CFRs were returned (58% response). 159 underwent diagnostic assessment, including 82 assessed in phase 1. All children meeting the criteria for autism identified via the Q-CHAT at phase 1 also met the criteria at phase 2. The PPV was 28% (95% CI 15% to 46%) after phase 1 and phase 2.ConclusionsThe Q-CHAT can be used at 18–30 months to identify autism and enable accelerated referral for diagnostic assessment. The low PPV suggests that for every true positive there would, however, be ~4–5 false positives. At follow-up, new cases were identified, illustrating the need for continued surveillance and rescreening at multiple time-points using developmentally sensitive instruments. Not all children who later receive a diagnosis of autism are detectable during the toddler period.

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MP09: Canadian Community Utilization of Stroke Prevention Pilot Study-Emergency Department (C-CUSP ED)

CJEM ◽

10.1017/cem.2017.175 ◽

2017 ◽

Vol 19 (S1) ◽

pp. S68 ◽

Cited By ~ 1

Author(s):

R. Parkash ◽

K. Magee ◽

M. McMullen ◽

M.B. Clory ◽

M. D’Astous ◽

...

Keyword(s):

Stroke Prevention ◽

Phase 1 ◽

Retrospective Chart Review ◽

Phase 2 ◽

Phase 3 ◽

Three Phase ◽

Rigorous Study ◽

The Mean ◽

Prior Risk

Introduction: Atrial fibrillation (AF) is the most common sustained arrhythmia affecting 1-2% of the population. Oral anticoagulation (OAC) reduces stroke risk by 60-80% in AF patients, but only 50% of indicated patients receive OAC. Many patients present to the ED with AF due to arrhythmia symptoms, however; lack of OAC prescription in the ED has been identified as a significant gap in the care of AF patients. Methods: This was a multi-center, pragmatic, three-phase before-after study, in three Canadian sites. Patients who presented to the ED with electrocardiographically (ECG) documented, nonvalvular AF and were discharged home were included. Phase 1 was a retrospective chart review to determine OAC prescription of AF patients in each ED; Phase 2 was a low-intensity knowledge translation intervention where a simple OAC-prescription tool for ED physicians with subsequent short-term OAC prescription was used, as well as an AF patient education package and a letter to family physicians; phase 3 incorporated Phase 2 interventions, but added immediate follow-up in a community AF clinic. The primary outcome of the study was the rate of new OAC prescriptions at ED discharge in AF patients who were OAC eligible and were not on OAC at presentation. Results: A total of 632 patients were included from June, 2015-November, 2016. ED census ranged from 30000-68000 annual visits. Mean age was 71±15, 67±12, 67±13 years, respectively. 47.5% were women, most responsible ED diagnosis was AF in 75.8%. The mean CHA2DS2-VASc score was 2.6±1.8, with no difference amongst groups. There were 266 patients eligible for OAC and were not on this at presentation. In this group, the prescription of new OAC was 15.8% in Phase 1 as compared to 54% and 47%, in Phases 2 and 3, respectively. After adjustment for center, components of the CHA2DS2-VASc score, prior risk of bleeding and most responsible ED diagnosis, the odds ratio for new OAC prescription was 8.0 (95%CI (3.5,18.3) p<0.001) for Phase 3 vs 1, and 10.0 (95%CI (4.4,22.9) p<0.001), for Phase 2 vs 1). No difference in OAC prescription was seen between Phases 2 and 3. Conclusion: Use of a simple OAC-prescription tool was associated with an increase in new OAC prescription in the ED for eligible patients with AF. Further testing in a rigorous study design to assess the effect of this practice on stroke prevention in the AF patients who present to the ED is indicated.

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A Phase 1/2 Trial of Pomalidomide, Dexamethasone and Pegylated Liposomal Doxorubicin for Patients with Relapsed/Refractory Multiple Myeloma

Blood ◽

10.1182/blood.v124.21.4774.4774 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4774-4774

Author(s):

James R. Berenson ◽

Laura V. Stampleman ◽

Alberto Bessudo ◽

Peter J. Rosen ◽

Leonard M Klein ◽

...

Keyword(s):

Multiple Myeloma ◽

Progressive Disease ◽

Liposomal Doxorubicin ◽

Phase 1 ◽

Single Agent ◽

Pegylated Liposomal Doxorubicin ◽

Great Promise ◽

Phase 2 ◽

Grade 3

Abstract Background Immunomodulatory drugs (IMiD), such as thalidomide and lenalidomide (LEN) and its newest derivative pomalidomide (POM), have shown great promise for the treatment of multiple myeloma (MM) patients (pts). POM has in vitro anti-MM potency and has shown efficacy for the treatment of relapsed/refractory (RR) MM pts. POM with dexamethasone (DEX) induces responses even for MM pts who are refractory to bortezomib (BORT) and LEN (Richardson et al, 2012). Pegylated liposomal doxorubicin (PLD) with BORT is FDA-approved for the treatment of MM pts who have received one prior therapy not containing BORT. The combination of PLD and LEN or thalidomide has shown efficacy for both RR and frontline MM pts (Offidani et al, 2006; 2007). We have also demonstrated that both the efficacy and tolerability of LEN in combination with DEX, PLD and BORT (DVD-R) may be improved by changing the doses and schedules of these drugs (Berenson et al, 2012). Based on these results, we hypothesized that the combination of POM, DEX and PLD would be effective for the treatment of RRMM pts. Thus, we conducted the first study investigating the safety and efficacy of POM in combination with intravenous (IV) DEX and PLD as a phase 1/2 trial using a modified dose, schedule and longer 28-day cycles for pts with RRMM. Methods The phase 1 portion enrolled MM pts w/ progressive disease whereas those enrolled in phase 2 also had to be refractory to LEN (single-agent or in combination), as demonstrated by progressive disease while receiving their last LEN-containing regimen or relapsed within 8 weeks of their last dose of this IMiD. Pts who have previously received POM treatment were ineligible. In the phase 1 portion, POM was administered at 2, 3 or 4 mg daily in three cohorts on days 1-21 of a 28-day cycle and DEX (40 mg) and PLD (5 mg/m2) were fixed and given intravenously on days 1, 4, 8, and 11. Results As of June 20th, 2014, 48 pts were enrolled in the trial and a total of 47 pts had received study drug. Pts had received a median of 4 prior treatments (range 1-18), with a median of 2 prior IMiD-containing regimens (range, 0-8). Fifty-three percent of the pts had received a prior PLD-containing regimen and 21% had received a prior IMiD and PLD combination treatment. Among all enrolled pts, 40 pts discontinued treatment and seven remain active. Pts completed a median of 3 cycles (range: 1-8), with a median follow-up time of 5.4 months (range: 0-22). During the phase 1 portion of the trial, the maximum tolerated dose (MTD) of POM was established at 4 mg. Enrollment of pts into the phase 2 portion of the trial began at the MTD. However, neutropenia ≥ grade 3 was observed at this dose in 10/17 (58.8%) phase 2 pts; and, as a result, the protocol was amended so that the MTD was lowered to 3 mg for all pts subsequently enrolled. Among the 36 pts enrolled in phase 2, 78% percent were refractory to LEN and steroids with or without other agents and 47% had previously received PLD. A median of 2 cycles (range, 1 to 8) were administered among the pts enrolled in phase 2. Thirty-five pts were evaluable for response as one pt was active but had not yet had any post-baseline disease assessments. Among all pts enrolled in phase 2, the overall response rate (ORR) and clinical benefit rate (CBR) were 29% and 49%, respectively, with 6 pts (17%) showing stable disease and 12 pts (34%) demonstrating progressive disease. For all pts enrolled in phase 2, the median follow-up time was 4.7 months (range 0-12) and the median PFS was 5.3 months. ORR and CBR for pts in the phase 2 were higher among pts receiving POM at 3 mg (32% and 58%, respectively) than among pts receiving POM at 4 mg (25% and 37%, respectively). Pts receiving the 4 mg dose of POM experienced more toxicities resulting in discontinuations, which likely explains the lower ORR and CBR observed among pts receiving this POM dose. Common ≥ grade 3 adverse events observed throughout the trial were neutropenia (21 pts; 44.7%), lymphopenia (10 pts; 21.3%), and hyponatremia (4 pts; 8.5%). One pt died of grade 5 sepsis. Conclusions This phase 1/2 trial is the first evaluating POM with PLD and DEX and demonstrates that the combination of POM at 3 mg, PLD and DEX using a modified 28-day cycle schedule is safe and effective for the treatment of MM pts refractory to LEN. Disclosures Berenson: Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau. Swift:Celgene: Consultancy, Honoraria. Vescio:Celgene: Honoraria.

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Improving eye health using a child-to-child approach in Bariadi, Tanzania

African Vision and Eye Health ◽

10.4102/aveh.v76i1.406 ◽

2017 ◽

Vol 76 (1) ◽

Cited By ~ 1

Author(s):

Ving F. Chan ◽

Hasan Minto ◽

Eden Mashayo ◽

Kovin S. Naidoo

Keyword(s):

Refractive Error ◽

Phase 1 ◽

Health Messages ◽

Eye Drops ◽

Vision Screening ◽

Phase 2 ◽

Eye Health ◽

Knowledge And Practice ◽

Two Phases

Purpose: Vision Champions (VC) are children trained to perform simple eye health screening and share eye health messages among their community. Our objectives were to assess the ability of VC in identifying and referring children and the community with refractive error and obvious ocular disease and to assess the change in knowledge and practice of eye healthseeking behaviour of the community 3 months after the introduction of the Vision Champion Programme.Methods: We purposively sampled 600 households and interviewed 1051 participants in two phases with a close-ended questionnaire. The numbers of children screened, referred by the VC and those who attended the Vision Centre were recorded. The percentage of people who answered the questions correctly were compared between Phase 1 (P1) and Phase 2 (P2).Results: The VC shared their eye health messages with 6311 people, screened 7575 people’s vision and referred 2433 people for further care. The community were more aware that using eye ointment not prescribed by doctors (P1 = 58.96% vs. P2 = 72.75%) can lead to blindness. Participants were more aware that they should not administer eye drops in stock (P1 = 44.18% vs. P2 = 61.37%) or received from a friend or relative (P1 = 53.23% vs. P2 = 72.35%) if their eyes are red and painful.Conclusion: Children have the potential to effectively share eye health messages and conduct simple vision screening for their families and peers. Efforts are needed to sensitise the community to improve the referral or follow-up rate.

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Minimally Invasive SPML Surgery for Children with Cerebral Palsy: Program Development

Minimally Invasive Surgery ◽

10.1155/2020/5124952 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Dana L. Wild ◽

Caroline W. Stegink-Jansen ◽

Christine P. Baker ◽

Kelly D. Carmichael ◽

David A. Yngve

Keyword(s):

Cerebral Palsy ◽

Minimally Invasive ◽

Phase 1 ◽

Case Series ◽

Functional Mobility ◽

Phase 2 ◽

Ankle Motion ◽

Case Series Study ◽

Reoperation Rates

Improvements in surgical and rehabilitation care are critical to lessen the burden of cerebral palsy (CP), the most common cause of severe physical disability in childhood. The selective percutaneous myofascial lengthening (SPML) surgical procedure is a minimally invasive method designed to improve ambulation by lengthening contracted musculoskeletal tissues. Information on surgical procedures, efficacy, and safety of SPML for children with CP is lacking. Phase 1 of our research is a “proof-of-principle” study for multisite SPML to improve functional mobility of children with CP, and Phase 2 assesses safety, reoperation rates, and efficacy over time in subsequent patient series. Phase 1 was a repeated measurement case series study of 17 children (mean age 7.6 years). One physical therapist, blinded to the surgeon’s measurements, measured bilateral knee and ankle motion before and after SPML procedures, using video recordings of a standardized gait path. Functional Mobility Scale (FMS) 5, 50, and 500 outcomes were taken pre- and postoperatively and via telephone follow-up. In Phase 2, multisite SPLM surgeries were implemented in larger successive cohorts from 2006 to 2017. Complications, reoperation rates, and efficacy were retrospectively analyzed. Phase 1 results showed improvement in the children’s knee and ankle motion while ambulating and improved FMS 5, 50, and 500 outcomes postoperatively (mean, 6.3 months). At second follow-up (mean 33.3 months), FMS 500 scores continued improvement, while FMS 5 and FMS 50 scores maintained. During Phase 2, the complication rate was 2.4%, and reoperation rates (including reoperations due to maturation) were between 8% and 13%. Improvements to correct ankle equinus were recorded in 498 cases. In conclusion, in a specialized center, single-event, multilevel SPML surgeries of children with CP safely improved ambulatory knee and ankle angle motion and daily mobility outcomes. Future educational studies of training needs for surgeons new to the approach are needed.

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A Feasible and Efficacious Mobile-Phone Based Lifestyle Intervention for Filipino Americans with Type 2 Diabetes: Randomized Controlled Trial (Preprint)

10.2196/preprints.8156 ◽

2017 ◽

Author(s):

Melinda S Bender ◽

Bruce A Cooper ◽

Linda G Park ◽

Sara Padash ◽

Shoshana Arai

Keyword(s):

Weight Loss ◽

Controlled Trial ◽

Phase 1 ◽

Intervention Group ◽

Filipino Americans ◽

Phase 2 ◽

Filipino American ◽

Potential Efficacy

BACKGROUND Filipino Americans have a high prevalence of obesity, type 2 diabetes (T2D), and cardiovascular disease compared with other Asian American subgroups and non-Hispanic whites. Mobile health (mHealth) weight loss interventions can reduce chronic disease risks, but these are untested in Filipino Americans with T2D. OBJECTIVE The objective of this study was to assess feasibility and potential efficacy of a pilot, randomized controlled trial (RCT) of a culturally adapted mHealth weight loss lifestyle intervention (Pilipino Americans Go4Health [PilAm Go4Health]) for overweight Filipino Americans with T2D. METHODS This was a 2-arm pilot RCT of the 3-month PilAm Go4Health intervention (phase 1) with an active waitlist control and 3-month follow-up (phase 2). The waitlist control received the PilAm Go4Health in phase 2, whereas the intervention group transitioned to the 3-month follow-up. PilAm Go4Health incorporated a Fitbit accelerometer, mobile app with diary for health behavior tracking (steps, food/calories, and weight), and social media (Facebook) for virtual social support, including 7 in-person monthly meetings. Filipino American adults ≥18 years with T2D were recruited from Northern California. Feasibility was measured by rates of recruitment, engagement, and retention. Multilevel regression analyses assessed within and between group differences for the secondary outcome of percent weight change and other outcomes of weight (kg), body mass index (BMI), waist circumference, fasting plasma glucose, HbA1c, and steps. RESULTS A total of 45 Filipino American adults were enrolled and randomized. Mean age was 58 (SD 10) years, 62% (28/45) were women, and mean BMI was 30.1 (SD 4.6). Participant retention and study completion were 100%, with both the intervention and waitlist group achieving near-perfect attendance at all 7 intervention office visits. Groups receiving the PilAm Go4Health in phase 1 (intervention group) and phase 2 (waitlist group) had significantly greater weight loss, −2.6% (−3.9 to −1.4) and −3.3% (−1.8 to −4.8), respectively, compared with the nonintervention group, resulting in a moderate to small effect sizes (d=0.53 and 0.37, respectively). In phase 1, 18% (4/22) of the intervention group achieved a 5% weight loss, whereas 82% (18/22) maintained or lost 2% to 5% of their weight and continued to maintain this weight loss in the 3-month follow-up. Other health outcomes, including waist circumference, BMI, and step counts, improved when each arm received the PilAm Go4Health, but the fasting glucose and HbA1c outcomes were mixed. CONCLUSIONS The PilAm Go4Health was feasible and demonstrated potential efficacy in reducing diabetes risks in overweight Filipino Americans with T2D. This study supports the use of mHealth and other promising intervention strategies to reduce obesity and diabetes risks in Filipino Americans. Further testing in a full-scale RCT is warranted. These findings may support intervention translation to reduce diabetes risks in other at-risk diverse populations. CLINICALTRIAL Clinicaltrials.gov NCT02290184; https://clinicaltrials.gov/ct2/show/NCT02290184 (Archived by WebCite at http://www.webcitation.org/6vDfrvIPp)

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Phase 2 and Later of COVID-19 Lockdown: Is it Possible to Perform Remote Diagnosis and Intervention for Autism Spectrum Disorder? An Online-Mediated Approach

Journal of Clinical Medicine ◽

10.3390/jcm9061850 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1850 ◽

Cited By ~ 3

Author(s):

Antonio Narzisi

Keyword(s):

Autism Spectrum Disorder ◽

Phase 1 ◽

Autism Spectrum ◽

Functional Adaptation ◽

Spectrum Disorder ◽

Phase 2 ◽

Older Children ◽

Working Models ◽

Communication Competencies ◽

Online Format

COVID-19 is still in phase 2. The lockdown has been significantly reduced compared to phase 1. The centers and institutions that deal with the diagnosis and intervention of children with autism spectrum disorder (ASD) require rapid functional adaptation to respond to patients’ needs. The possibility of using technology to activate and manage diagnostic (preliminary diagnosis) and intervention processes should be explored. Two developed telemedicine working models for diagnosis and intervention, including synchronous and asynchronous transmissions, are presented. They are proposals not yet supported by the data. The diagnosis step is composed by two different and consecutives phases: (A) pre-specialistic consultation (PSC) and (B) specialistic assessment. The intervention step implemented well-recognized evidence-based models for preschoolers, school-aged, and older children in an online format. Parents’ support is also included. The described working models have the purpose of carrying out preliminary specialistic answers to the families without aiming to replace preferable in-person assessment. Based on previous research findings, the telemedicine approach is accepted by parents, increases their sense of competence, increases the parent intervention adhesion, and improves the social communication competencies for children with ASD. In conclusion, the presented working models must be considered partial responses to the current emergency status and at the same time as possible integrations into traditional approaches.

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LO58: Long-term outcomes among emergency department syncope patients: a systematic review

CJEM ◽

10.1017/cem.2018.120 ◽

2018 ◽

Vol 20 (S1) ◽

pp. S27-S27

Author(s):

C. Leafloor ◽

P. Jiho Hong ◽

L. Sikora ◽

J. Elliot ◽

M. Mukarram ◽

...

Keyword(s):

Systematic Review ◽

Emergency Department ◽

Phase 1 ◽

Adverse Outcomes ◽

Cochrane Central Register ◽

Phase 2 ◽

Long Term Outcomes ◽

One Year

Introduction: Approximately 50% of patients discharged from the Emergency Department (ED) after syncope have no cause found. Long-term outcomes among syncope patients are not well studied, to guide physicians regarding outpatient testing and follow-up. The objective of this study was to conduct a systematic review for long-term (one year) outcomes among ED patients with syncope. We aim to use the results of this review to guide us in prospective analysis of one year outcomes with our large database of syncope patients. Methods: We searched Cochrane Central Register of Controlled Trials, Medline and Medline in Process, PubMed, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) from the inception to June, 2017. We included studies that reported long-term outcomes among adult ED patients (16 years or older) with syncope. We excluded studies on pediatric patients, and studies that included syncope mimickers: pre-syncope, seizure, intoxication, loss of consciousness after head trauma. We also excluded case reports, letters to the editor and review articles. Outcomes included death, syncope recurrence requiring hospitalization, arrhythmias and procedural interventions for arrhythmias. We selected articles based on title and abstract review during phase-1 and conducted full article review during phase-2. Meta-analysis was performed by pooling the outcomes using random effects model (RevMan v.5.3; Cochrane Collaboration). Results: Initial literature search generated 2094 articles after duplicate removal. 50 articles remained after phase-1 (=0.85) and 16 articles were included in the systematic review after phase-2 (=0.86). The 16 included studies enrolled a total of 44,755 patients. Pooled analysis at 1-year follow-up showed the following outcomes: 7% mortality; 14% recurrence of syncope requiring hospitalization; one study reported that 0.6% of patients had a pacemaker inserted; and two studies reported 0.8 11.5% of patients suffered new arrhythmias. Conclusion: An important proportion of ED patients with syncope suffer outcomes at 1-year. Appropriate follow-up is needed to prevent long-term adverse outcomes. Further prospective research to identify patients at risk for long-term important cardiac outcomes and death is needed.

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Phase 2 dose multi-center, open-label study of ARQ 501, a checkpoint activator, in adult patients with persistent, recurrent or metastatic leiomyosarcoma (LMS)

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.20521 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 20521-20521 ◽

Cited By ~ 15

Author(s):

L. P. Hartner ◽

L. Rosen ◽

M. Hensley ◽

D. Mendelson ◽

A. P. Staddon ◽

...

Keyword(s):

Clinical Investigation ◽

Phase 1 ◽

Phase 2 ◽

Open Label ◽

Open Label Study ◽

Apoptotic Protein ◽

Three Phase ◽

Phase 2 Study ◽

Lost To Follow Up

20521 Background: ARQ 501 selectively induces apoptosis in cancer cells by inducing a rapid and sustained increase of the pro- apoptotic protein E2F-1. ARQ 501 has been studied in three phase 1 studies, demonstrating acceptable toxicity and encouraging signs of efficacy. A 54 y/o female with metastatic LMS who failed 7 previous therapies achieved a prolonged PR on ARQ 501 monotherapy. This was consistent with preclinical data, where induction of E2F-1 and corresponding efficacy in human leiomyosarcoma xenografts was observed. Methods: A phase 2 study in adult LMS patients (>3 prior systemic therapies) was initiated to assess ORR, TTP and further characterize the safety of ARQ 501. ORR included CR, PR and SD=4 mo. Four week cycles (ARQ 501 450mg/m2) were repeated until progression, unacceptable toxicity, or another discontinuation criterion. Results: 49 patients were enrolled and 45 received ARQ 501. Data is available for 43 patients (4M/39F, median age, 54). Of the 43, 10 did not reach a protocol defined tumor assessment (4 deaths, 5 PD and 1 lost to follow-up prior to week 8), 19 have been assessed for response per RECIST at eight weeks (7 SD of 8–28+ weeks, 1 PR, 11 PD) and 14 active patients yet to reach first tumor assessment. The most common AEs were: anemia (68%, 21%=G3), hyperbilirubinemia (35%, 6%=G3), fatigue (35%, 0%=G3), nausea (30%, 0%=G3), constipation (24%), hemolysis (21%, 6%=G3), dyspnea (21%), and vomiting (21%). One treatment related death was reported in a 47 y/o Asian male with severe hemolysis following a single infusion of ARQ 501 at 450 mg/m2. The pt was hospitalized, but severe hemolysis led to acute renal failure and the patient expired after 4 days. Conclusions: ARQ 501 was administered to 45 patients with advanced, recurrent or persistent leiomyosarcoma. Several patients have achieved some clinical benefit (1 PR, 3 prolonged SD), further analysis of efficacy data is warranted prior to additional clinical investigation. No significant financial relationships to disclose.

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Outcomes of patients (pts) ≥ 65 years of age in ZUMA-1, a pivotal phase 1/2 study of axicabtagene ciloleucel (axi-cel) in refractory large B-cell lymphoma (LBCL).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.7555 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 7555-7555

Author(s):

Sattva Swarup Neelapu ◽

Caron A. Jacobson ◽

Olalekan O. Oluwole ◽

Javier Munoz ◽

Abhinav Deol ◽

...

Keyword(s):

T Cell ◽

Phase 1 ◽

Objective Response ◽

B Cell Lymphoma ◽

Phase 2 ◽

T Cell Therapy ◽

Car T Cell ◽

Car T ◽

Grade 3

7555 Background: Axi-cel is a US FDA-approved, autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy for the treatment of pts with relapsed or refractory LBCL with ≥ 2 prior systemic therapies. In the 2-y follow-up of ZUMA-1, the objective response rate (ORR) was 83% with a complete response (CR) rate of 58%, and 39% of pts were in ongoing response (Locke et al. Lancet Oncol. 2019). Here we report efficacy and safety outcomes by age. Methods: Eligible pts with refractory LBCL underwent leukapheresis and conditioning chemotherapy followed by a target dose of 2 × 106 anti-CD19 CAR T cells/kg. The Phase 2 primary endpoint was investigator-assessed ORR. Additional key endpoints were adverse events (AEs), overall survival (OS), and levels of CAR gene-marked cells in peripheral blood. Efficacy was evaluated for Phase 2 pts; safety was evaluated for all treated pts (Phases 1 and 2). Pts were analyzed by ≥ 65 y vs < 65 y of age. Results: As of 8/11/2018, 108 pts were treated. Pts ≥ 65 y (n = 27) vs < 65 y (n = 81) had a median age of 69 y vs 55 y, respectively, were 81% vs 63% male, 70% vs 36% had an IPI score 3-4, 59% vs 57% had ECOG 1, 67% vs 72% had ≥ 3 prior therapies, and median tumor burdens were 3790 mm2 vs 3574 mm2. Median follow-up was 27.1 mo for Phase 2 pts (n = 101). The ORR for pts ≥ 65 y (n = 24) and < 65 y (n = 77) was 92% and 81% (CR rate 75% and 53%), respectively, with ongoing responses in 42% and 38% of pts (ongoing CR 42% and 35%). The 24-mo OS rate was 54% for pts ≥ 65 y and 49% for pts < 65 y. Most pts experienced Grade ≥ 3 AEs (100% of pts ≥ 65 y; 98% of pts < 65 y), and 4% of each group (1/27 pts ≥ 65 y and 3/81 pts < 65 y) died due to AEs as previously reported. Grade ≥ 3 neurologic events and cytokine release syndrome occurred in 44% vs 28% and 7% vs 12% of pts ≥ 65 y vs < 65 y, respectively. CAR T cell expansion by peak level (43 vs 35 cells/μl) or area under the curve (562 vs 448 d × cells/μl) was similar in pts ≥ 65 y vs < 65 y, respectively. Conclusions: The 2-y follow-up of ZUMA-1 demonstrates that axi-cel can induce high rates of durable responses with a manageable safety profile for pts ≥ and < 65 y. Axi-cel offers substantial clinical benefit for older pts with refractory LBCL who otherwise have limited treatment options. Clinical trial information: NCT02348216.

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SPEARHEAD-1: A phase 2 trial of afamitresgene autoleucel (Formerly ADP-A2M4) in patients with advanced synovial sarcoma or myxoid/round cell liposarcoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.11504 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 11504-11504

Author(s):

Sandra P. D'Angelo ◽

Brian Andrew Van Tine ◽

Steven Attia ◽

Jean-Yves Blay ◽

Sandra J. Strauss ◽

...

Keyword(s):

T Cells ◽

Synovial Sarcoma ◽

Phase 1 ◽

Low Grade ◽

Phase 2 ◽

Round Cell ◽

Cytokine Release ◽

Cytokine Release Syndrome ◽

Wide Range

11504 Background: This phase 2, open-label trial (SPEARHEAD-1; NCT04044768) is designed to evaluate the efficacy, safety, and tolerability of afamitresgene autoleucel in 45 patients (pts) with advanced/metastatic synovial sarcoma or Myxoid/Round Cell Liposarcoma (MRCLS). Methods: Eligible pts are HLA-A*02 positive with MAGE-A4-expressing tumors. Pts undergo leukapheresis for collection of autologous T-cells for processing and manufacture into afamitresgene autoleucel cells. Pts were treated with afamitresgene autoleucel doses between 1–10 × 109 transduced T-cells after receiving lymphodepleting chemotherapy. The primary endpoint is overall response rate per RECIST v1.1 by independent review. An independent Data Safety Monitoring Board reviews ongoing safety and benefit: risk during the interventional phase. Results: As of Feb 4, 2021, 32 pts received afamitresgene autoleucel. Of these pts, 59% were male, 87.5% had synovial sarcoma, the median age was 43 yrs (range: 24–73), and they had a median of 3 prior systemic lines of therapy. The MAGE-A4 antigen expression level (histoscore) ranged from 112–300, and the transduced cell dose ranged from 2.7–9.9 x 109. At the data cutoff, 25 pts were evaluable for preliminary efficacy (23 with synovial sarcoma and 2 with MRCLS) and 7 pts (5 with synovial sarcoma and 2 with MRCLS) had insufficient follow-up (<8 weeks follow-up and/or awaiting first scan). Of the 25 evaluable pts, the investigator-assessed responses were: complete response (2 pts), partial response (8 pts), stable disease (11 pts), and progressive disease (4 pts). All responses were confirmed. Nine of the 10 responders had ongoing response at the data cutoff and 3 responders had MAGE-A4 antigen histoscores <200. The most common AEs of any grade (>30% pts) were neutropenia, lymphopenia, nausea, cytokine release syndrome, leukopenia, fatigue, pyrexia, and anemia. Cytokine release syndrome of any grade occurred in 19/32 pts; 95% of those events were ≤Grade 2. No immune effector cell-associated neurotoxicity syndrome (ICANS) has been reported to date. Cytopenia (≥G3) at 4 wks post-infusion was observed in 6 pts (anemia 3 pts, neutropenia 2 pts, and thrombocytopenia 1 pt). Conclusion: These preliminary data demonstrate afamitresgene autoleucel is efficacious and well tolerated in heavily pre-treated pts. Objective responses are reported across a wide range of MAGE-A4 antigen levels and deep responses have been observed. Initial durability data is encouraging. Preliminary response data in SPEARHEAD-1 is comparable to the findings of the prior Phase 1 trial [1]. To date, the safety profile of afamitresgene autoleucel has been favorable, with mainly low-grade cytokine release syndrome and tolerable/reversible hematologic toxicities. [1]. Van Tine BA, et al. CTOS; November 18-21, 2020; Virtual. Clinical trial information: NCT04044768.

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