A global phase III multicenter, randomized, double-arm, open label trial of ASP-1929 photoimmunotherapy versus physician’s choice standard of care for the treatment of patients with locoregional, recurrent head and neck squamous cell carcinoma (rHNSCC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS6094-TPS6094 ◽  
Author(s):  
Merrill A. Biel ◽  
Ann M. Gillenwater ◽  
David M. Cognetti ◽  
Jennifer Maria Johnson ◽  
Athanassios Argiris ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Controlled Trial ◽  
Standard Of Care ◽  
Light Treatment ◽  
Phase Iii ◽  
Tumor Cell Death ◽  
Open Label ◽  
Combination Drug ◽  
Phase 3 ◽  
Curative Therapy

TPS6094 Background: rHNSCC commonly affects local or regional sites and is associated with considerable morbidity and mortality. Outcomes of these patients remain poor with limited curative treatment options and low response rates. New modalities that are targeted, minimally invasive, and provide improved tumor response and control while having limited systemic side effects are needed. Photoimmunotherapy (PIT) is a new cancer-targeted platform technology. It is a combination drug and device treatment that utilizes monoclonal antibodies conjugated to a dye (IRDye 700DX) that is photoactivated using nonthermal red light to induce rapid and selective tumor cell death. The objective of this phase 3 study is to evaluate the efficacy and safety of ASP-1929 (EGFR-directed antibody cetuximab-IR700 conjugate) PIT treatment as a monotherapy in patients with locoregional rHNSCC. Methods: A global, multicenter phase 3, randomized, double-arm, open-label, controlled trial of ASP-1929 PIT vs physician’s choice standard of care (SOC) for the treatment of locoregional, rHNSCC in patients who have failed or progressed on or after at least two lines of therapy, of which at least one line must be systemic therapy, is currently underway. Primary endpoints of the study are PFS and OS and the key secondary endpoint is ORR. Key inclusion criteria include: disease not amenable to curative therapy; tumor(s) accessible for PIT light treatment and measurable by CT or MRI; male or female ≥ 18 yrs old with life expectancy > 6 months; ECOG score of 0 to 1. Key exclusion criteria include: history of ≥ Grade 3 cetuximab infusion reaction; distant metastatic disease; tumors invading a major blood vessel unless embolized. The study will include ~275 subjects in a 2:1 randomization (ASP-1929 PIT: Physician’s choice SOC). The physician’s choice SOC arm includes cetuximab, methotrexate, or docetaxel. Tumor(s) are illuminated with 690 nm PIT light treatment 24 hrs following completion of ASP-1929 infusion (640 mg/m²). Clinical trial sites will be in the USA, EU and Asia. Clinical trial information: NCT03769506.

scholarly journals Unfractionated heparin in acute chest syndrome: a pilot feasibility randomized controlled trial of unfractionated heparin vs. standard of care in acute chest syndrome

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Craig D. Seaman ◽  
Enrico Novelli ◽  
Laura De Castro ◽  
Margaret V. Ragni
Keyword(s):  
Unfractionated Heparin ◽  
Large Scale ◽  
Controlled Trial ◽  
Standard Of Care ◽  
Phase Iii ◽  
Therapeutic Modality ◽  
Red Blood Cell Transfusion ◽  
Acute Chest Syndrome ◽  
Open Label ◽  
Randomized Controlled

Abstract Background Acute chest syndrome (ACS) is the leading cause of mortality in sickle cell disease (SCD). The pathogenesis of ACS is complex and not entirely understood with multiple etiologies likely contributing simultaneously. One particular etiology is pulmonary vascular occlusion due to thrombosis. Thus, anticoagulation is an attractive therapeutic modality. Methods This was a single-center, randomized controlled, open-label, pilot study to determine the feasibility of performing a larger multicenter phase III trial to assess the effects of unfractionated heparin (UFH) in ACS. Subjects were randomized within 24 h of diagnosis of ACS to one of two treatment arms, UFH, and standard of care (SOC), or no UFH and SOC. UFH was given intravenously for 7 days, or until discharge, if discharge was shorter than 7 days. SOC consisted of intravenous fluids, antibiotics, supplemental oxygen, analgesia, red blood cell transfusion, and exchange transfusion. Results From July 2014 to June 2018, a total of 7 patients underwent randomization (four patients received UFH in addition to SOC and 3 patients received SOC only). Two of the prespecified feasibility criteria were not met: the capacity to consent eligible individuals and the timely notification of hospitalized patients with ACS necessary to permit randomization within 24 h of diagnosis; thus, as a result of poor enrollment, the study was terminated early. The duration of hospitalization was 279.43 (SD 267.98) and 127.31 (SD 137.70) h in the UFH and SOC arms, respectively. The duration of hypoxemia, leukocytosis, fever, and moderate to severe pain was 117.52 (SD 60.52), 24.90 (SD 29.69), 117.52 (SD 60.52), and 117.52 (SD 60.52) h, respectively, in the UFH group, and 51.49 (SD 44.79), 0, 53.11 (SD 25.06), and 88.68 (SD 72.77) h, respectively, in the SOC group. No major bleeding was noted in either group. Conclusions Our study did not achieve prespecified feasibility criteria, resulting in poor enrollment and early termination, and serves to highlight some of the pitfalls experienced in clinical research in SCD. It did show the use of UFH without any major adverse events in 7 subjects. No future large-scale study is planned. Trials registration Registered at ClinicalTrials.gov (NCT #02098993) on March 28, 2014.

Bortezomib, lenalidomide, and dexamethasone (VRd) ± daratumumab (DARA) in patients (pts) with transplant-eligible (TE) newly diagnosed multiple myeloma (NDMM): A multicenter, randomized, phase III study (PERSEUS).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS8055-TPS8055 ◽  
Author(s):  
Pieter Sonneveld ◽  
Annemiek Broijl ◽  
Francesca Gay ◽  
Mario Boccadoro ◽  
Hermann Einsele ◽  
...  
Keyword(s):  
Stem Cell ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Open Label ◽  
Phase 3 ◽  
Related Quality ◽  
Duration Of Response ◽  
Line Of Therapy

TPS8055 Background: DARA, a human, CD38-targeting, IgGκ monoclonal antibody, is approved in many countries for use as monotherapy in relapsed/refractory MM (RRMM), and in combination with standard-of-care regimens in RRMM and transplant-ineligible NDMM. Given the initial safety and efficacy observed with DARA plus VRd (D-VRd) in the safety run-in cohort of the ongoing phase 2 GRIFFIN study in TE NDMM pts, the phase 3 PERSEUS study will evaluate the efficacy and safety of D-VRd versus VRd alone in TE NDMM. Methods: This is an ongoing multicenter, open-label, randomized phase 3 study of D-VRd versus VRd alone in TE NDMM pts. Approximately 690 pts across Europe will be stratified by ISS stage and cytogenetic risk (high risk defined as presence of del17p, t[4;14], or t[14;16]) and randomized in a 1:1 ratio. All pts will receive VRd (V: 1.3 mg/m2 SC Days 1, 4, 8, 11; R: 25 mg PO Days 1-21; d: 40 mg PO Days 1-4, 9-12) for 4 pre-transplant induction and 2 post-transplant consolidation cycles (all 28-d cycles), followed by R (10 mg PO Days 1-28) maintenance until progressive disease (PD). Pts in the DARA group will also receive subcutaneous DARA (1,800 mg co-formulated with recombinant human hyaluronidase PH20 [rHuPH20; Halozyme]) QW in Cycles 1-2, Q2W in Cycles 3-6, and Q4W in maintenance Cycles 7+ until PD. After induction, pts will undergo melphalan 200 mg/m2 conditioning and autologous stem cell transplantation (ASCT). Pts in the DARA group who achieve sustained minimal residual disease (MRD) negativity (10–5 threshold; assessed by NGS) for 12 months after ≥24 months of maintenance will stop DARA but continue R maintenance until PD; upon loss of CR or MRD-negative status, pts will restart DARA treatment. All pts will receive preinfusion medications. The primary endpoint is progression-free survival (PFS). Secondary endpoints include MRD-negative rate, overall response rate, PFS on next line of therapy, overall survival, time to and duration of response, health-related quality of life, pharmacokinetics, immunogenicity, stem cell yield after mobilization, time to engraftment post-ASCT, and safety. Clinical trial information: NCT03710603.

scholarly journals Evaluation of convalescent plasma versus standard of care for the treatment of COVID-19 in hospitalized patients: study protocol for a phase 2 randomized, open-label, controlled, multicenter trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Elena Diago-Sempere ◽  
José Luis Bueno ◽  
Aránzazu Sancho-López ◽  
Elena Múñez Rubio ◽  
Ferrán Torres ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Respiratory Infections ◽  
Controlled Trial ◽  
Standard Of Care ◽  
Viral Disease ◽  
Multicenter Trial ◽  
Adult Patients ◽  
Ordinal Scale ◽  
Efficacy And Safety ◽  
Open Label

Abstract Background COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. At the time this clinical trial was planned, there were no available vaccine or therapeutic agents with proven efficacy, but the severity of the condition prompted the use of several pharmacological and non-pharmacological interventions. It has long been hypothesized that the use of convalescent plasma (CP) from infected patients who have developed an effective immune response is likely to be an option for the treatment of patients with a variety of severe acute respiratory infections (SARI) of viral etiology. The aim of this study is to assess the efficacy and safety of convalescent plasma in adult patients with severe COVID-19 pneumonia. Methods/design The ConPlas-19 study is a multicenter, randomized, open-label controlled trial. The study has been planned to include 278 adult patients hospitalized with severe COVID-19 infection not requiring mechanical ventilation (invasive or non-invasive). Subjects are randomly assigned in a 1:1 ratio (139 per treatment arm), stratified by center, to receive intravenously administered CP (single infusion) plus SOC or SOC alone, and are to be followed for 30 days. The primary endpoint of the study is the proportion of patients that progress to category 5, 6, or 7 (on the 7-point ordinal scale proposed by the WHO) at day 15. Interim analyses for efficacy and/or futility will be conducted once 20%, 40%, and 60% of the planned sample size are enrolled and complete D15 assessment. Discussion This clinical trial is designed to evaluate the efficacy and safety of passive immunotherapy with convalescent plasma for the treatment of adult patients hospitalized with COVID-19. The results of this study are expected to contribute to establishing the potential place of CP in the therapeutics for a new viral disease. Trial registration ClinicalTrials.gov NCT04345523. Registered on 30 March, 2020. First posted date: April 14, 2020.

scholarly journals Randomized controlled trial of convalescent plasma therapy against standard therapy in patients with severe COVID-19 disease

2020 ◽  
Author(s):  
Manaf AlQahtani ◽  
Abdulkarim Abdulrahman ◽  
Abdulrahman Almadani ◽  
Salman Yousif Alali ◽  
Alaa Mahmood Al Zamrooni ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Standard Therapy ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Severe Disease ◽  
Pilot Trial ◽  
Secondary Outcome ◽  
Open Label ◽  
Phase 3 ◽  
Plasma Therapy

AbstractBackgroundConvalescent plasma (CP) therapy in COVID-19 disease has been suggested to improve clinical outcome in severe disease. This pilot study was designed to inform the design of a definitive phase 3 clinical trial.MethodsThis was a prospective, interventional and randomized open label pilot trial involving 40 patients with COVID-19 who were requiring oxygen therapy and who had radiological evidence of pneumonia. Twenty COVID-19 patients received two 200ml transfusions of convalescent patient CP over 24 hours were compared with 20 patients who received routine care alone. The primary outcome was the requirement for ventilation. The secondary outcomes were white blood cell count, lactate dehydrogenase (LDH), C-reactive protein (CRP), Troponin, Ferritin, D-Dimer, procalcitonin, mortality rate at 28 days.ResultsThe CP group were a higher risk group with higher ferritin levels (p<0.05) though respiratory indices did not differ. The primary outcome measure – ventilation – was required in 6 controls and 4 patients on CP (risk ratio 0.67 95% CI 0.22 – 2.0, p=0.72); mean time on ventilation was 10.5 days in the control against 8.2 days in patients on CP (p=0.81). There were no differences in secondary measures at the end of the study. Two patients died in the control and one patient in the CP arm.ConclusionThere were no significant differences in the primary or secondary outcome measures between CP and standard therapy though fewer patients required ventilation and for a shorter period of time. The study showed that CP therapy appears to be safe and it is feasible to perform a definitive phase 3 clinical trial using this study protocol.

scholarly journals Direct antivirals working against the novel coronavirus: azithromycin (DAWn-AZITHRO), a randomized, multicenter, open-label, adaptive, proof-of-concept clinical trial of new antivirals working against SARS-CoV-2—azithromycin trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Iwein Gyselinck ◽  
◽  
Laurens Liesenborghs ◽  
Ewout Landeloos ◽  
Ann Belmans ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Standard Of Care ◽  
Ordinal Scale ◽  
Cytokine Signaling ◽  
Nasopharyngeal Swab ◽  
The Novel ◽  
Proof Of Concept ◽  
Open Label ◽  
Novel Coronavirus

Abstract Background The rapid emergence and the high disease burden of the novel coronavirus SARS-CoV-2 have created a medical need for readily available drugs that can decrease viral replication or blunt the hyperinflammatory state leading to severe COVID-19 disease. Azithromycin is a macrolide antibiotic, known for its immunomodulatory properties. It has shown antiviral effect specifically against SARS-CoV-2 in vitro and acts on cytokine signaling pathways that have been implicated in COVID-19. Methods DAWn-AZITHRO is a randomized, open-label, phase 2 proof-of-concept, multicenter clinical trial, evaluating the safety and efficacy of azithromycin for treating hospitalized patients with COVID-19. It is part of a series of trials testing promising interventions for COVID-19, running in parallel and grouped under the name DAWn-studies. Patients hospitalized on dedicated COVID wards are eligible for study inclusion when they are symptomatic (i.e., clinical or radiological signs) and have been diagnosed with COVID-19 within the last 72 h through PCR (nasopharyngeal swab or bronchoalveolar lavage) or chest CT scan showing typical features of COVID-19 and without alternate diagnosis. Patients are block-randomized (9 patients) with a 2:1 allocation to receive azithromycin plus standard of care versus standard of care alone. Standard of care is mostly supportive, but may comprise hydroxychloroquine, up to the treating physician’s discretion and depending on local policy and national health regulations. The treatment group receives azithromycin qd 500 mg during the first 5 consecutive days after inclusion. The trial will include 284 patients and recruits from 15 centers across Belgium. The primary outcome is time from admission (day 0) to life discharge or to sustained clinical improvement, defined as an improvement of two points on the WHO 7-category ordinal scale sustained for at least 3 days. Discussion The trial investigates the urgent and still unmet global need for drugs that may impact the disease course of COVID-19. It will either provide support or else justify the discouragement of the current widespread, uncontrolled use of azithromycin in patients with COVID-19. The analogous design of other parallel trials of the DAWN consortium will amplify the chance of identifying successful treatment strategies and allow comparison of treatment effects within an identical clinical context. Trial registration EU Clinical trials register EudraCT Nb 2020-001614-38. Registered on 22 April 2020

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