Search

Access to commercial CD19 CAR-T cells remains limited even in wealthy countries like Canada due to clinical, logistical, and financial barriers related to centrally manufactured products. We created a non-commercial academic platform for end-to-end manufacturing of CAR-T cells within Canada’s publicly funded healthcare system. We report initial results from a single-arm, open-label study to determine the safety and efficacy of in-house manufactured CD19 CAR-T cells (entitled CLIC-1901) in participants with relapsed/refractory CD19 positive hematologic malignancies. Using a GMP compliant semi-automated, closed process on the Miltenyi Prodigy, T cells were transduced with lentiviral vector bearing a 4-1BB anti-CD19 CAR transgene and expanded. Participants underwent lymphodepletion with fludarabine and cyclophosphamide, followed by infusion of non-cryopreserved CAR-T cells. Thirty participants with non-Hodgkin’s lymphoma (n=25) or acute lymphoblastic leukemia (n=5) were infused with CLIC-1901: 21 males (70%), median age 66 (range 18-75). Time from enrollment to CLIC-1901 infusion was a median of 20 days (range 15-48). The median CLIC-1901 dose infused was 2.3 × 106 CAR-T cells/kg (range 0.13-3.6 × 106/kg). Toxicity included ≥ grade 3 cytokine release syndrome (n=2) and neurotoxicity (n=1). Median follow-up was 6.5 months. Overall response rate at day 28 was 76.7%. Median progression-free and overall survival was 6 months (95%CI 3-not estimable) and 11 months (95% 6.6-not estimable), respectively. This is the first trial of in-house manufactured CAR-T cells in Canada and demonstrates that administering fresh CLIC-1901 product is fast, safe, and efficacious. Our experience may provide helpful guidance for other jurisdictions seeking to create feasible and sustainable CAR-T cell programs in research-oriented yet resource-constrained settings.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03765177, identifier NCT03765177.

Traditionally, economic evaluations have engaged clinicians and policymakers; however, patients and their caregivers have insight that can ensure that the economic evaluation process appropriately reflects disease consequences and adequately addresses their priorities related to treatment.We aimed to identify patient priorities to inform an early economic evaluation of chimeric antigen receptor T-cell therapy for adults with relapsed or refractory B-cell acute lymphoblastic leukemia.We conducted two online group discussions of four participants each, involving patients with experience of hematological cancer and a caregiver. We used an adapted version of the nominal group technique, a consensus-building discussion approach, to generate focused qualitative data.Patients and a caregiver acknowledged both the costs directly related to clinical care, such as the out-of-pocket cost of drugs, and the indirect treatment costs, such as the cost of transport, accommodation, and food. The emotional and physical toll of treatment and the influence of treatment on employment and education were additional costs emphasized by participants. Treatment benefits prioritized by participants included the efficacy of treatment, manageable side effects, improved quality of life, accessibility of treatment, and short treatment duration.Engaging patients and caregivers in an early economic evaluation could help identify additional costs and benefits of therapies that are not typically recognized in economic evaluations but have the potential to increase the commercial viability of novel therapies. This research also demonstrates how patients and caregivers can be engaged at different levels in the development of early economic evaluation models.

Patients want personalized information before surgery; most do not receive personalized risk estimates. Inadequate information contributes to poor experience and medicolegal complaints. We hypothesized that exposure to the Personalized Risk Evaluation and Decision Making in Preoperative Clinical Assessment (PREDICT) app, a personalized risk communication tool, would improve patient knowledge and satisfaction after anesthesiology consultations compared with standard care. We conducted a prospective clinical study (before-after design) and used patient-reported data to calculate personalized risks of morbidity, mortality, and expected length of stay using a locally calibrated National Surgical Quality Improvement Program risk calculator embedded in the PREDICT app. In the standard care (before) phase, the application’s materials and output were not available to participants; in the PREDICT app (after) phase, personalized risks were communicated. Our primary outcome was knowledge score after the anesthesiology consultation. Secondary outcomes included patient satisfaction, anxiety, feasibility, and acceptability. We included 183 participants (90 before; 93 after). Compared with standard care phase, the PREDICT app phase had higher post-consultation: knowledge of risks (14.3% higher; 95% confidence interval [CI], 6.5 to 22.0; P < 0.001) and satisfaction (0.8 points; 95% CI, 0.1 to 1.4; P = 0.03). Anxiety was unchanged (− 1.9%; 95% CI, − 4.2 to 0.5; P = 0.13). Acceptability was high for patients and anesthesiologists. Exposure to a patient-facing, personalized risk communication app improved knowledge of personalized risk and increased satisfaction for adults before elective inpatient surgery. www.clinicaltrials.gov (NCT03422133); registered 5 February 2018.

Engaging patients as partners in the design and execution of early-phase clinical trials offers a unique opportunity to ensure patient perspectives are considered. Here we describe our experience partnering with four individuals with lived experience of blood cancer to co-develop documents and services to support participants of an early-phase trial. Through regular team meetings, patient partners co-developed a visual informed consent document and a non-technical summary of the informed consent document to facilitate participant understanding of trial procedures. Overall, patient partners highlighted important trial components that would not have been identified without their input.

Aim Though patient engagement in clinical research is growing, recent reports suggest few clinical trials report on such activities. To address this gap, we describe our approach to patient engagement in the development of a clinical trial protocol to assess a new immunotherapy for blood cancer (chimeric antigen receptor T-cell therapy, CAR-T cell therapy). Methods Our team developed a clinical trial protocol by working with patient partners from inception. Two patient partners with lived blood cancer experience were identified through referrals from our team’s professional network and patient organization contacts. Our patient partners were onboarded to the team and engaged in several studies conducted to develop the clinical trial protocol, including a systematic review of the existing literature on the therapy, patient interviews and a survey to obtain perspectives on barriers and enablers to participating in the trial, an early economic analysis, and a retrospective cohort study. Results Engaging patient partners enhanced our research in ways that would not have otherwise occurred. By selecting patient important outcomes for data collection, our partners helped flag that quality of life and health utility measures have not been reported in previous CAR-T cell therapy trials for blood cancer. Our partners also co-developed a non-technical summary of the systematic review that summarized results in an accessible manner. Our patient partners reviewed interview and survey questions, to improve the language and appropriateness; provided recruitment suggestions; and provided a patient perspective on the results, thereby confirming the importance of findings. Input was also obtained on costs for the early economic analysis. Our patient partners identified costs that may be a burden to both patients and caregivers during a trial and helped to confirm that the overall structure of the economic model reflected the patient care pathway. Our patient partners also shared their diagnosis and treatment stories, which helped to provide the research team with insight into this experience. Conclusions Contributions by our patient partners were invaluable to each component study, as well as the overall development of the trial protocol. We plan to use this approach in the future in order to meaningfully engage patients in the development of other clinical trials; we also hope that by reporting our methods this will help other research teams to do the same. Trial registration Affiliated with the development of NCT03765177.

Aim: Though patient engagement in clinical research is growing, recent reports suggest few clinical trials report on such activities. To address this gap, we describe our approach to patient engagement in the development of a clinical trial protocol for a new immunotherapy for blood cancer (chimeric antigen receptor T-cell therapy, CAR-T cell therapy). Methods: Our team developed a clinical trial protocol by working with patient partners from inception. Two patient partners with lived blood cancer experience were identified through referrals from our team’s professional network and patient organization contacts. Our patient partners were onboarded to the team and engaged in several studies conducted to develop the clinical trial protocol, including a systematic review of the existing literature on the therapy, patient interviews and a survey to obtain perspectives on barriers and enablers to participating in the trial, an early economic analysis, and a retrospective cohort study. Results: Engaging patient partners enhanced our research in ways that would not have otherwise occurred. By selecting patient important outcomes for data collection, our partners helped flag that quality of life and health utility measures have not been reported in previous CAR-T cell therapy trials for blood cancer. Our partners also co-developed a non-technical summary of the systematic review that summarized results in an accessible manner. Our patient partners reviewed interview and survey questions, to improve the language and appropriateness; provided recruitment suggestions; and provided a patient perspective on the results, thereby confirming the importance of findings. Input was also obtained on costs for the early economic analysis. Our patient partners identified costs that may be a burden to both patients and caregivers during a trial and helped to confirm that the overall structure of the economic model reflected the patient care pathway. Our patient partners also shared their diagnosis and treatment stories, which helped to provide the research team with insight into this experience.Conclusions: Contributions by our patient partners were invaluable to each component study, as well as the overall development of the trial protocol. We plan to use this approach in the future, to meaningfully engage patients in the development of other clinical trials; we also hope that by reporting our methods this will help other research teams to do the same. Trial Registration: Affiliated with the development of NCT03765177

Aim: Though patient engagement in clinical research is growing, recent reports suggest few clinical trials report on such activities. To address this gap, we describe our approach to patient engagement in the development of a clinical trial protocol for a new immunotherapy for blood cancer (chimeric antigen receptor T-cell therapy, CAR-T cell therapy). Methods: Our team developed a clinical trial protocol by working with patient partners from inception. Two patient partners with lived blood cancer experience were identified through referrals from our team’s professional network and patient organization contacts. Our patient partners were onboarded to the team and engaged in several studies conducted to develop the clinical trial protocol, including a systematic review of the existing literature on the therapy, patient interviews and a survey to obtain perspectives on barriers and enablers to participating in the trial, an early economic analysis, and a retrospective cohort study. Results: Engaging patient partners enhanced our research in ways that would not have otherwise occurred. By selecting patient important outcomes for data collection, our partners helped flag that quality of life and health utility measures have not been reported in previous CAR-T cell therapy trials for blood cancer. Our partners also co-developed a non-technical summary of the systematic review that summarized results in an accessible manner. Our patient partners reviewed interview and survey questions, to improve the language and appropriateness; provided recruitment suggestions; and provided a patient perspective on the results, thereby confirming the importance of findings. Input was also obtained on costs for the early economic analysis. Our patient partners identified costs that may be a burden to both patients and caregivers during a trial and helped to confirm that the overall structure of the economic model reflected the patient care pathway. Our patient partners also shared their diagnosis and treatment stories, which helped to provide the research team with insight into this experience.Conclusions: Contributions by our patient partners were invaluable to each component study, as well as the overall development of the trial protocol. We plan to use this approach in the future, to meaningfully engage patients in the development of other clinical trials; we also hope that by reporting our methods this will help other research teams to do the same. Trial Registration: Affiliated with the development of NCT03765177

Patients want personalized information before surgery; most do not receive personalized risk estimates. Inadequate information contributes to poor experience and medicolegal complaints. We hypothesized that exposure to the Personalized Risk Evaluation and Decision Making in Preoperative Clinical Assessment (PREDICT) app, a personalized risk communication tool, would improve patient knowledge and satisfaction after anesthesiology consultations compared with standard care.We conducted a prospective clinical study (before-after design) and used patient-reported data to calculate personalized risks of morbidity, mortality, and expected length of stay using a locally calibrated National Surgical Quality Improvement Program risk calculator embedded in the PREDICT app. In the standard care (before) phase, the application's materials and output were not available to participants; in the PREDICT app (after) phase, personalized risks were communicated. Our primary outcome was knowledge score after the anesthesiology consultation. Secondary outcomes included patient satisfaction, anxiety, feasibility, and acceptability.We included 183 participants (90 before; 93 after). Compared with standard care phase, the PREDICT app phase had higher post-consultation: knowledge of risks (14.3% higher; 95% confidence interval [CI], 6.5 to 22.0; P0.001) and satisfaction (0.8 points; 95% CI, 0.1 to 1.4; P = 0.03). Anxiety was unchanged (- 1.9%; 95% CI, - 4.2 to 0.5; P = 0.13). Acceptability was high for patients and anesthesiologists.Exposure to a patient-facing, personalized risk communication app improved knowledge of personalized risk and increased satisfaction for adults before elective inpatient surgery.www.clinicaltrials.gov (NCT03422133); registered 5 February 2018.RéSUMé: OBJECTIF: Les patients veulent disposer d’informations personnalisées avant leur chirurgie, mais la plupart d’entre eux ne reçoivent pas d’estimations de leur risque personnalisées. Des informations inadéquates contribuent à une mauvaise expérience et à des plaintes médicolégales. Nous avons émis l’hypothèse qu’une exposition à l’application PREDICT (Personalized Risk Evaluation and Decision Making in Preoperative Clinical Assessment), un outil de communication du risque personnalisé, améliorerait les connaissances et la satisfaction des patients après leurs consultations en anesthésiologie comparativement à des soins standard. MéTHODE: Nous avons réalisé une étude clinique prospective (de type avant-après) et utilisé les données rapportées par les patients afin de calculer leur risque personnalisé de morbidité et de mortalité, ainsi que la durée de séjour anticipée à l’aide d’un calculateur de risque tiré du Programme national d’amélioration de la qualité chirurgicale que nous avons calibré localement et intégré à l’application PREDICT. Dans la phase de soins standard (avant), le contenu et les résultats de l’application n’étaient pas divulgués aux participants; dans la phase comportant l’application PREDICT (après), les risques personnalisés étaient communiqués. Notre critère d’évaluation principal était le score des connaissances des patients après la consultation en anesthésiologie. Les critères d’évaluation secondaires comprenaient la satisfaction des patients et leur niveau d’anxiété ainsi que la faisabilité et l’acceptabilité d’une telle approche. RéSULTATS: Nous avons inclus 183 participants (90 avant; 93 après). Comparativement à la phase de soins standard, la phase avec l’application PREDICT a démontré un niveau plus élevé de connaissances des risques post consultation (14,3 % plus élevé; intervalle de confiance [IC] 95 %, 6,5 à 22,0; P0,001) et de satisfaction (0,8 point; IC 95 %, 0,1 à 1,4; P = 0,03). L’anxiété est demeurée inchangée (− 1,9 %; IC 95 %, − 4,2 à 0,5; P = 0,13). L’acceptabilité était élevée, tant chez les patients que chez les anesthésiologistes. CONCLUSION: L’exposition des patients à une application de communication du risque personnalisé a amélioré leurs connaissances de leur risque personnalisé et augmenté la satisfaction des adultes avant une chirurgie non urgente et non ambulatoire. ENREGISTREMENT DE L’éTUDE: www.clinicaltrials.gov (NCT03422133); enregistrée le 5 février 2018.