Evaluation of the Impact of the Presence of Neutralizing L-Asparaginase Antibodies on the Efficacy and Safety of Graspa in Phase 3 Randomized Trial Versus Native L-Asparaginase in Patients with Relapsed Acute Lymphoblastic Leukemia (NCT01518517)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3734-3734 ◽  
Author(s):  
Yves Bertrand ◽  
Andre Baruchel ◽  
Xavier Thomas ◽  
Nicolas Blin ◽  
Emmanuelle Tavernier ◽  
...  
Keyword(s):  
Lymphoblastic Leukemia ◽  
Clinical Signs ◽  
Phase Iii ◽  
Disease Rate ◽  
Clinical Activity ◽  
Induction Phase ◽  
Hypersensitivity Reactions ◽  
Phase 3 ◽  
The Mean ◽  
The Impact

Abstract Background Asparaginase is a cornerstone in the treatment of ALL, but its utility is limited by toxicities including hypersensitivity. Clinical allergy is associated with inactivation of asparaginase by antibodies, which can also neutralize asparaginase without any clinical signs of hypersensitivity (silent inactivation). GRASPA (eryaspase - proposed INN) is an L-asparaginase encapsulated into the red blood cells. In a recent Phase III trial, it has shown to prolong the asparaginase activity and significantly reduce the incidence of allergic reactions in pts with relapsed ALL. Methods This open, randomized international Phase 3 study enrolled pts with relapsed ALL. The co-primary endpoints were the mean duration of asparaginase (ASPA) activity > 100 IU/L and incidence of hypersensitivity reactions during induction phase. Key secondary endpoints were safety, tolerability, complete remission and minimal residual disease rate, PK, and anti-ASPA antibodies (A-Abs) at baseline. Pts (n=80), aged 1-55 years without prior hypersensitivity were randomized to GRASPA (150 IU/kg, n=26, Arm A) or native L-asparaginase (L-ASP, 10,000 IU/m², n=28, Arm B). Additionally, 26 pts with prior hypersensitivity were treated with GRASPA in a single stratum (Arm C). All pts received COOPRALL protocol as a backbone chemotherapy. Here we report the impact of A-Abs on safety and efficacy of GRASPA. Assessments were performed at Day 4, 13, 18, and 27 (F1/F2 block), Day 6, 15, and 27 (VANDA block), and Day 6, 12 (R2/R1 block). Results At baseline, 23%, 25%, and 58% of pts had +ve A-Abs status in Arms A, B, and C, respectively. The mean duration of total ASPA activity (Days) adjusted for baseline antibody status is presented below, and shows that activity slightly differed with positive status; however, GRASPA maintained higher activity compared to L-ASP: Table 1. GRASPA L-ASP GRASPA L-ASP GRASPA (Arm C) Antibody status Negative Positive Negative Positive N 20 21 6 7 11 15 Mean (SD) 22.4 (3.6) 10.31 (8.1) 14.17 (5.1) 6.5 (4.0) 18.9 (6.8) 18.4 (6.2) Median 22.4 8.3 12.2 7.0 21.8 21.7 Min; Max 10.2; 30.7 0.0; 25.0 9.8; 21.8 1.9; 14.0 9.1; 27.9 6.9; 25.0 The incidence of hypersensitivity reactions were 0%, 7/21 (33%), and 2/11 (18%) in pts with negative A-Abs, compared to 0%, 6/7 (85.7%), and 1/15 (7%) in pts with positive A-Abs, in arms A, B and C, respectively. The CR rate during induction was 75%, 48%, and 64% in pts with negative A-Abs, compared to 33%, 14% and 48% in pts with positive A-Abs, in arms A, B and C, respectively. Conclusion These results show that about one third of pts without evidence of prior hypersensitivity have silent A-Abs activation. Positive A-Abs appeared to attenuate the clinical activity in all treatments arms. GRASPA consistently demonstrated activity and improved hypersensitivity regardless of A-Abs status, and therefore, GRASPA is a suitable option for patients with relapsed ALL. Disclosures Bertrand: ERYTECH Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Thomas:ERYTECH Pharma: Consultancy. Vey:Celgene: Honoraria; Roche: Honoraria; Janssen: Honoraria. Bonin:ERYTECH Pharma: Employment. Godfrin:ERYTECH Pharma: Employment. El Hariry:ERYTECH Pharma: Employment.

Pharmacokinetic and Pharmacodynamic Characterization of Graspa Versus Native L-Asparaginase in Combination with Cooprall Chemotherapy in a Phase 3 Randomized Trial for the Treatment of Patients with Relapsed Acute Lymphoblastic Leukemia (NCT01518517)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2492-2492 ◽  
Author(s):  
Xavier Thomas ◽  
Yves Bertrand ◽  
Andre Baruchel ◽  
Nicolas Blin ◽  
Emmanuelle Tavernier ◽  
...  
Keyword(s):  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Clinical Signs ◽  
Phase Iii ◽  
Disease Rate ◽  
P Value ◽  
Induction Phase ◽  
Phase 3 ◽  
Logrank Test ◽  
Asparaginase Activity

Abstract Background Asparaginase is a cornerstone in the treatment of ALL, but its utility is limited by toxicities including hypersensitivity. Clinical allergy is associated with inactivation of asparaginase by antibodies, which can also neutralize asparaginase without any clinical signs of hypersensitivity (silent inactivation). GRASPA (eryaspase - proposed INN) is an L-asparaginase encapsulated into the red blood cells. In a recent Phase III trial, it has shown to prolong the asparaginase activity and significantly reduce the incidence of allergic reactions in pts with relapsed ALL. Methods This open, randomized international Phase 3 study enrolled pts with relapsed ALL. The co-primary endpoints were the mean duration of asparaginase (ASPA) activity > 100 IU/L and incidence of hypersensitivity reactions during induction phase. Key secondary endpoints were safety, tolerability, complete remission and minimal residual disease rate, pharmacokinetic (PK), pharmacodynamics (PD) and anti-ASPA antibodies at baseline. Pts (n=80), aged 1-55 years without prior hypersensitivity were randomized to GRASPA (150 IU/kg, n=26, Arm A) or native L-asparaginase (L-ASP, 10,000 IU/m², n= 28, Arm B). Additionally, 26 pts with prior hypersensitivity were treated with GRASPA in a single stratum (Arm C, GRASPA-s). All pts received COOPRALL protocol as a backbone chemotherapy. Here we report the report the PK of asparaginase activity, and PD effects. Results A total of 80 pts enrolled into the trial. A total 100% and 96% of patients had at least one day with asparaginase level >100 IU/L during induction, with GRASPA and L-ASP, respectively. Only one patient in L-Asp group did not reach this threshold. All patients in Arm C have also achieved total blood asparaginase level > 100 IU/L during induction. Prolonged ASPA activity was maintained across several key subpopulations as follows: Table 1. GRASPA L-ASP GRASPA L-ASP Age group Children Adults  N 21 21 5 7  Mean (SD) 20.8 (5.3) 11.4 (7.3) 19.3 (5.5) 3.2 (2.8)  Median 22.0 8.3 22.1 2.3 Risk Score S1/S2 S3/S4  N 16 15 10 13  Mean (SD) 20.2 (6.0) 12.0 (8.6) 20.9 (3.9) 6.3 (4.4)  Median 22.4 9.0 22.0 6.2 F1-F2/VANDA F1-F2 VANDA  N 16 15 10 13  Mean (SD) 19.5 ± 6.5 11.5 (9.0) 22.0 (0.2) 6.9 (4.2)  Median 22.9 8.8 22.0 6.9 The total ASPA activity >100 IU/L until the loss of that activity demonstrated that the activity was retained in the majority of pts in the GRASPA arm (89%) compared to only 26% in the L-ASP arm. The median times from first assessment of activity > 100 IU/L to loss of activity was not reached in the GRASPA arm by Day 28, but was 15 days in the L-ASP arm. The difference was statistically significant (table below). Similar trend was also observed with GRASPA-s. Table 2. Time from first assessment showing ASPA activity > 100 IU/L until loss of ASPA activity > 100 IU/L Number (%) of events Median [95% CI] Hazard ratio 95% CI Logrank test: p-value for superiority L-ASPN= 28 27 (96.4) 15[11; 21] 0.14 0.07, 0.28 <0.001 GRASPAN= 26 26 (100) NR* NR: not reached Additional information correlating ASPA with asparagine depletion and other amino acid changes (aspartate, glutamic acid, and glutamate) will be provided at the meeting. Conclusion GRASPA consistently demonstrated activity compared to L-ASP for the treatment of pts with relapsed ALL, and is therefore a suitable option for patients with relapsed ALL. Disclosures Thomas: ERYTECH Pharma: Consultancy. Bertrand:ERYTECH Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Vey:Celgene: Honoraria; Roche: Honoraria; Janssen: Honoraria. Bonin:ERYTECH Pharma: Employment. Godfrin:ERYTECH Pharma: Employment. El Hariry:ERYTECH Pharma: Employment.

scholarly journals Updated Clinical Activity of Graspa Versus Native l-Asparaginase in Combination with Cooprall Regimen in Phase 3 Randomized Trial in Patients with Relapsed Acute Lymphoblastic Leukemia (NCT01518517)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3723-3723 ◽  
Author(s):  
Andre Baruchel ◽  
Yves Bertrand ◽  
Xavier Thomas ◽  
Nicolas Blin ◽  
Emmanuelle Tavernier ◽  
...  
Keyword(s):  
Relapse Rate ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Clinical Signs ◽  
Phase Iii ◽  
Induction Treatment ◽  
Clinical Activity ◽  
P Value ◽  
Phase 3 ◽  
Alternative Treatment Option

Abstract Background Asparaginase is a cornerstone in the treatment of ALL, but its utility is limited by toxicities including hypersensitivity. Clinical allergy is associated with inactivation of asparaginase by antibodies, which can also neutralize asparaginase without any clinical signs of hypersensitivity (silent inactivation). GRASPA (proposed eryaspase, E-Coli L-Asparaginase encapsulated into red blood cells) improves pharmacokinetics, tolerability and maintain circulating asparaginase (ASPA) activity due to the protective barrier of the erythrocyte membrane. In a recent Phase III trial, it has shown to prolong the asparaginase activity and significantly reduce the incidence of allergic reactions in pts with relapsed ALL. In the non-allergic pts, GRASPA significantly reduced the incidence of hypersensitivity (0% vs 46%; p<0.001). ASPA activity >100 IU/l was 21 ± 5 vs 9 ± 7 days in GRASPA and L-ASP, respectively (p<0.001). Methods This open, randomized international Phase 3 study enrolled pts with relapsed ALL. The co-primary endpoints were the duration of ASPA activity > 100IU/L and the incidence of hypersensitivity during induction. Key secondary endpoints were complete remission, minimal residual disease, relapse rate, event free survival (EFS) and overall survival (OS). Pts (n=80), aged 1-55 years without prior hypersensitivity were randomized to GRASPA (150 IU/kg, n=26, Arm A) or native L-asparaginase (L-ASP, 10,000 IU/m², n= 28, Arm B). Additionally, 26 pts with prior hypersensitivity were treated with GRASPA in a single stratum (Arm C). All pts received COOPRALL protocol as a backbone chemotherapy. Results A total of 80 pts with relapsed and or refractory ALL were enrolled into the trial. There were a greater proportion of pts who completed the induction treatment in GRASPA arm (65%) than in the L-ASP arm (46%). The main reasons for treatment discontinuation were: target levels of asparagine depletion not reached (64%) in GRASPA arm, and adverse events (58%) in the L-ASP arm. In addition, in the L-ASP arm, 5 (19%) pts prematurely discontinued treatment due to disease progression. As of the cut-off date (28th August 2014), the majority of pts (63%) still continued in the study and followed-up for survival. The relapse rate at 6 and 12 mo was low, and accounted for 3 (13%; 95% CI: 2.6; 32.4) and 5 (26%; 95% CI: 9.1; 51.2) in the GRASPA arm, compared to 1 pt (5%) and 3 (17%; 95% CI: 3.6; 41.4) in the L-ASP arm, respectively. Except for L-ASP, and adult patients, the median EFS and OS were not reached for GRASPA in the entire set or in children, either at 12 months. Overall, there was a trend across all groups with lower EFS and OS event rates with GRASPA compared to L-ASP, as presented in table below. The 2-year follow up will be additionally provided at the meeting Table 1. GRASPA vs L-ASP All patients GRASPA = 26 L-ASP = 28 Children GRASPA = 21 L-ASP = 21 Adults GRASPA = 5 L-ASP = 7 12 mo EFS Median (mo) NR vs 11.6 NR 4.6 vs 1.6 Events 30.8% vs 50.0% 19.1% vs 38.1% 80% vs 85.7% HR 0.54 0.47 0.69 95% CI 0.23; 1.26 0.15; 1.47 0.20; 2.44 P Value* 0.153 0.196 0.569 12 mo OS Median (mo) NR NR 10 vs 8.2 Events 23.1% vs 32.1% 4.8% vs 14.3% 20% vs 42.8% HR 0.63 0.34 0.39 95% CI 023; 1.74 0.05; 2.42 0.05; 2.81 P Value* 0.377 0.424 0.705 *P value in all subsets is not statistically significant Conclusion GRASPA has demonstrated both safety and activity in pts with relapsed ALL, and provides an alternative treatment option for those patients. Disclosures Bertrand: ERYTECH Pharma: Consultancy. Thomas:ERYTECH Pharma: Consultancy. Vey:Roche: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Bonin:ERYTECH Pharma: Employment. El Hariry:ERYTECH Pharma: Employment.

scholarly journals The ‘Vero Cell’ COVID-19 vaccine rollout in Nepal: What we know about the Chinese vaccine development and access?

2021 ◽  
Vol 8 (1) ◽  
pp. 1-8
Author(s):  
Jay Narayan Shah
Keyword(s):  
Clinical Trial ◽  
United Arab Emirates ◽  
Science And Technology ◽  
Modern Science ◽  
Phase Iii ◽  
Phase 3 ◽  
Pharmaceutical Group ◽  
Fda Approval ◽  
The Usa ◽  
The Impact

The world has changed dramatically from the impact of the COVID-19. It has impacted the normality of daily life, highlighting the failure of rich and poor nations alike, which is evident from the high number of human lives lost in rich and powerful countries like the USA with total deaths of 32,735,704 and Europe with 43,708,958 until April 24, 2021, as per Worldometer. The COVID-19 pandemic has shown that all of us ‘have and have-not’, no one can escape from the effects of the lockdowns, disruption of normal life including education, businesses, etc. reminding all of us that equitable access to vaccines is the best possible choice not to further exacerbate the challenges because ‘no country is safe until every country is safe’. It is a remarkable scientific achievement that within a year of the identification of the virus, we have COVID-19 vaccines, albeit available mostly in rich countries. The benefit of research is possible only with solidarity, by sharing the available resources, vaccine included, for the control of the ongoing COVID-19 pandemic. Modern science and technology, including the development and marketing of COVID-19 vaccines, have been focused in the USA and Europe. China joined this club of elites of science following the Chinese FDA approval of Sinopharm (the subsidiary of state-owned China National Pharmaceutical Group- CNPG), first COVID-19 vaccine (inactivated Sars-Cov-2) based on the results of the phase-3 clinical trial in UAE and Bahrain showing up to 86% efficacy of the vaccine in preventing COVID-19. Detail of trials of Sinopharm inactivated COVID-19 vaccines (Vero Cells) available on two early trials in China (Phase I/II ChiCTR2000031809, enrollment 1,456) and later 4 trials outside China (phase III, NCT04510207 Bahrain, Egypt, Jordan, United Arab Emirates- enrollment of 45,000; ChiCTR2000034780 United Arab Emirates, enrollment of 15,000; NCT04612972 Peru, enrollment of 6,000) show the progress of research and approval in China and UAE. Modern science and technology, including the development and marketing of COVID-19 vaccines, have been focused in the USA and Europe. China joined this club of elites of science following the Chinese FDA approval of Sinopharm (the subsidiary of state-owned China National Pharmaceutical Group- CNPG) first COVID-19 vaccine (inactivated Sars-Cov-2) based on the results of the phase-3 clinical trial in UAE and Bahrain showing up to 86% efficacy of the vaccine in preventing COVID-19.3

Impact of PSMA PET/CT on SRT planning: Preliminary results from the randomized phase III trial NCT03582774.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 30-30
Author(s):  
Jeremie Calais ◽  
Wesley R Armstrong ◽  
Amar Upadhyaya Kishan ◽  
Kiara M Booker ◽  
David Elashoff ◽  
...  
Keyword(s):  
Success Rate ◽  
Phase Iii ◽  
Open Label ◽  
Phase 3 ◽  
Preliminary Results ◽  
Volume Delineation ◽  
Psma Pet ◽  
Pet Ct ◽  
The Impact

30 Background: The purpose of this trial is to evaluate the success rate of salvage radiation therapy (SRT) for recurrence of prostate cancer (PCa) after radical prostatectomy with and without planning based on prostate specific membrane antigen (PSMA) positron emission tomography (PET). Methods: This is a multicenter, prospective, randomized, controlled, open-label, Phase 3 clinical imaging trial powered for clinical outcome at 5 years. UCLA is the leading central site in which PSMA PET, clinical follow-up and data management are being done. UCSF was a participating site in which PSMA PET imaging can be done. SRT can be performed anywhere, patients are followed remotely by the UCLA investigators. Patients scheduled for SRT for recurrence after primary prostatectomy and with PSA ≥ 0.1ng/ml at time of enrollment were eligible. Patients were randomized to proceed with standard SRT allowing for any conventional imaging aside from PSMA PET/CT (control arm) or undergo a 68Ga-PSMA-11 PET/CT scan prior to SRT planning (investigational arm). The primary endpoint is the success rate of SRT at 5 years in patients who undergo SRT. We report here the preliminary results of a secondary endpoint: the impact of PSMA PET on SRT planning by comparing the pre-randomization RT plans prospectively obtained on surveys before randomization to the actually delivered RT plans obtained after follow-up. Results: Enrollment of the trial was complete. 193 patients were enrolled from 09.06.2018 to 08.17.2020. 7/90 patients (9%) in the control arm dropped-out the study because they underwent a PSMA PET at another institution, while 1/103 (1%) patients of the intervention arm dropped-out due to COVID-19 related complications. After a median follow-up of 13.3 months (last follow-up date 09/01/2020), delivered RT plans were obtained in 60/83 (72%) and 70/102 (69%) of patients of the control and the PSMA arms, respectively. Median PSA at enrollment was 0.32 ng/ml (IQR 0.17-1.35) and 0.22 ng/ml (IQR 0.14-0.50) in the control and PSMA arms, respectively. There was a change between the intended pre-randomization RT plan and the actually delivered RT plan in 17/60 (28%) and 40/70 (57%) of the patients in the control and PSMA arms, respectively (p = 0.002). SRT was aborted in favor of systemic therapy and/or metastasis directed RT for extra-pelvic M1 disease in 2/60 (3%) and 12/70 (17%) of the control and PSMA arms, respectively (p = 0.17). Dose prescription and/or target volume delineation was changed in 2/60 (3%) and 1/70 (26%) in the control and PSMA arms, respectively (p = 0.001). Conclusions: In this prospective randomized phase 3 study, PSMA PET had an impact on the SRT plan in more than half of the patients. Long-term follow-up will show if the impact of PSMA PET on SRT planning translates into improved outcome or not. Clinical trial information: NCT03582774.

Financial sustainability of NHS Foundation Trusts in England five years after the enactment of the Health and Social Care Act of 2012

2019 ◽  
Vol 25 (6) ◽  
pp. 1-9
Author(s):  
Rachael S Coates ◽  
Reza Mofidi
Keyword(s):  
Structural Changes ◽  
Social Care ◽  
Clinical Activity ◽  
Financial Indicators ◽  
Financial Position ◽  
Total Capital ◽  
Health And Social Care ◽  
The Mean ◽  
Foundation Trusts ◽  
The Impact

Background/Aims The enactment of the Health and Social Care Act (2012) led to significant structural changes in how hospital services are commissioned and has introduced direct competition with the private sector. The aim of this study was to assess the impact of the act on the financial position of the Shelford Group of NHS Trusts, 5 years after the act's enactment. Methods The levels of clinical activity, annual accounts and statements of financial position produced by the 10 Trusts for the financial years 2010/2011 to 2017/2018 were examined. Findings The key financial indicators for each organisation were collected. Key financial indicators for the period just before the Act were compared with the corresponding values for the period of 5 years after the enactment of the Act. The Shelford group of NHS Trusts provided 15 047 304 patient care episodes in 2017/2018, which represented a rise of 6.34% over 5 years. This was a significant slowdown in clinical, which had grown by 18.57% in the 4 years immediately before the act. There were no significant differences in the mean operating surplus returned by the Shelford Group in the 5 years after the Act, compared to before its implementation. The median cost of finance for each organisation increased by 35.4% from £18 245 000 to £24 703 000. The total capital employed remained static over the 5 years following enactment of the Act. There were no significant differences in levels of liquidity and leverage of the Shelford Group in the 5 years after the Act compared to before. Conclusions The financial position of the Shelford Group of Trusts has not been adversely affected by the Health and Social Care Act (2012) , although there was some evidence that the operational finances of these NHS Trusts were less robust in the 5 years following the Act.

MRD-Detection by Multiparametric Flow Cytometry in Childhood Precursor B-Cell All:Predictive Impact of Early Blast Reduction Kinetics in Peripheral Blood (PB) on MRD-Level in Bone Marrow (BM) at Day 33 of the All-BFM2000 Potocol.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 987-987
Author(s):  
Richard Ratei ◽  
Mathilde Martin ◽  
Guiseppe Basso ◽  
Guiseppe Gaipa ◽  
Martin Schrappe ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Phase I ◽  
Correlation Coefficient ◽  
Induction Therapy ◽  
Lymphoblastic Leukemia ◽  
Induction Phase ◽  
Spearman Correlation ◽  
Multiparametric Flow Cytometry ◽  
Cell Counts ◽  
The Impact

Abstract Detection of minimal residual disease in childhood acute lymphoblastic leukemia (ALL) has been proven to be of crucial importance for relapse prediction. However, MRD assessment, usually performed at postinduction time points, does not allow early stratification of induction therapy. Here, we address the predictive impact of early blast reduction in pB on BM MRD-levels at the end of induction therapy phase I (d33), quantified by multiparametric flow cytometry (MFC-MRD). Absolute blast cell counts (BCC, blasts/μl) in pB at diagnosis and day 8 as well as MRD-levels in BM and pB at day 15 and 33 were determined in a series of 77 consecutive patients (pts.) enrolled in the AIEOP-BFM-FCM-MRD pilot study (BM d33:MRD+ n=29, MRD- n=48). Blast cells were detected using a two platform method and a 4-color antibody panel with three follow-up tubes:1) CD20-FITC/CD10-PE/CD34-PC5/CD19-PC7, 2) CD58-FITC/CD10-PE/ CD34-PC5/CD19-PC7, 3) CD10-FITC/CD11a-PE/CD45-PC5/CD19-PC7. Additionally, staining with the cell permeant live-cell nucleic acid fluorochrome SYTO 16 combined with CD19 or CD3 and CD45 were used to exclude residual non-nucleated erythroid cells, platelets or debris from absolute blast calculations. We found that BCC in BM and pB at d15 but not at diagnosis and after prednisone prephase at day 8 correlated with MRD-levels in BM at d33 (Spearman correlation coefficient rs=0.41, p<0.001 and rs=0,30, p<0,01). In order to further investigate the impact of early blast reduction between day 0 and day 8 we calculated the relative blast reduction rate on day 8 (BRRd8 = 1-BCCd8/BCCd0). In the group of MRD-negative patients the mean values of BRRd8 were found to be significantly higher than in the group of MRD-positive pts. (98,9% vs. 88,0%, p< 0,05). Moreover, the BRRd8 correlated with MRD-levels in BM at day 33 (Spearman correlation coefficient rs=−0.25, p<0.05). In the current series of pts. maximally selected log-rank statistics were performed for the BRRd8 and the MRD-level in BM at d33 and provided a cut-off value of 97% separating MRD-positive and MRD-negative pts. In conclusion, the assessment of the dynamics of early blast reduction with the parameter of BRRd8 is highly predictive for the outcome of induction phase I of the ALL-BFM2000 protocol.

Hospitalization for patients in the United States (US) and European Union (EU) treated with inotuzumab ozogamicin (InO) vs standard of care (SOC) for relapsed/refractory acute lymphoblastic leukemia (R/R ALL) in a global phase 3 trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18500-e18500 ◽  
Author(s):  
Yun Su ◽  
Ilse van Oostrum ◽  
Erik Vandendries ◽  
Verna Welch ◽  
Fausto Rodriguez Loberiza
Keyword(s):  
Treatment Period ◽  
Lymphoblastic Leukemia ◽  
The United States ◽  
Cost Driver ◽  
Clinical Activity ◽  
Phase 3 ◽  
Entire Treatment Period ◽  
Patient Reported ◽  
The Us ◽  
The Eu

e18500 Background: InO, an anti-CD22 antibody-calicheamicin conjugate, with its once a week, 1-hour infusion schedule, has demonstrated lower hospital utilization in association with superior clinical activity, favorable patient-reported outcomes (PROs), and a generally manageable safety profile versus SOC (intensive chemotherapy) for R/R ALL in the phase 3 INO-VATE trial. Here, regional-specific hospitalizations in the trial are presented. Methods: Patients receiving study treatment and recruited from the US and the EU were included in the analyses. The total number of days hospitalized for each patient was calculated. Hospital days prior to randomization and those after the end of study treatment were excluded. Due to different treatment durations for InO and SOC (median 1 vs 3 cycles), calculations were reported for cycle 1 treatment period (randomization to end of cycle 1) and for the entire treatment period (all cycles - randomization to end of treatment). Results: A total of 281 patients were available for the analyses. 154 were from the US and 127 from 11 of the EU countries. The median and mean hospitalization days were shorter for patients in the InO arm compared to the SOC arm across both regions (Table). The difference between the two treatment arms appear to be greater in the US compared to the EU. Hospitalizations in the US appear to be shorter than in the EU, particularly for patients receiving InO. Conclusions: InO treatment in R/R ALL is associated with less hospitalization across both the US and EU compared to SOC, consistent with InO’s better efficacy, tolerability, PRO and dosing schedule. The finding that US has lower hospitalization than the EU might be explained by different patient care practices in the two regions. Given that hospitalization is the biggest cost driver in cancer care, the discrepancy may lead to greater cost-savings in healthcare systems where hospitalizations are strictly managed. Clinical trial information: NCT01564784. [Table: see text]

Analysis of racial distribution amongst patients in phase III cancer clinical trials.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6588-6588 ◽  
Author(s):  
Swathi Gopishetty ◽  
Shruti Gupta ◽  
Vamsi Kota ◽  
Achuta Kumar Guddati
Keyword(s):  
Clinical Trials ◽  
Lymphoblastic Leukemia ◽  
Geographical Location ◽  
Racial Diversity ◽  
B Cell Lymphoma ◽  
Phase Iii ◽  
Cancer Clinical Trials ◽  
Phase 3 ◽  
Asian Patients ◽  
Organ Specific

6588 Background: Minority races are often under-represented in cancer clinical trials as enrollment often occurs in large centers. Racial diversity may vary by geographical location and socio-economically backward areas may have a very different racial mix. This study explores the representation of different races in phase 3 clinical trials conducted in the past 10 years. Methods: Details about adult patients involved in phase 3 trials was extracted from the clinical trials.gov for 3 common solid organs and 3 hematological malignancies [breast, colon, lung, diffuse large B-cell lymphoma (DLBCL), acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL)]. The racial distribution of the patient population in these trials was analyzed. Results: African American and Asian patients are under-represented in all phase 3 cancer clinical trials. The table shows the average racial distribution in clinical trials for each organ specific malignancy. Conclusions: Most phase 3 clinical trials except for lung cancer, predominantly consisted of Caucasian patients. Applying the results of these trails to patients of other races should be done with caution. This study highlights the disparity of race in patients enrolled in clinical trials when compared to diverse and different populations that are encountered in practice. [Table: see text]

A phase III study (COSMIC-313) of cabozantinib (C) in combination with nivolumab (N) and ipilimumab (I) in patients (pts) with previously untreated advanced renal cell carcinoma (aRCC) of intermediate or poor risk.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. TPS767-TPS767 ◽  
Author(s):  
Toni K. Choueiri ◽  
Laurence Albiges ◽  
Thomas Powles ◽  
Christian Scheffold ◽  
Fong Wang ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Prognostic Score ◽  
Geographic Region ◽  
Phase Iii ◽  
Clinical Activity ◽  
Phase 3 ◽  
Double Blind ◽  
Poor Risk ◽  
Recist 1.1 ◽  
Flat Dose

TPS767 Background: C inhibits tyrosine kinases involved in tumor growth, angiogenesis, and immune regulation, including MET, VEGFR, and TAM kinases (Tyro3, AXL, MER), and may promote an immune-permissive tumor environment, resulting in enhanced response to immune checkpoint inhibitors. C has shown preliminary clinical activity and tolerability in combination with the PD-1 inhibitor N and as part of a triplet combination with N and the CTLA-4 inhibitor I in pts with aRCC (Nadal et al. ASCO 2018). C is approved for pts with aRCC, and N+I is approved as a combination therapy in pts with previously untreated aRCC of intermediate or poor risk. We present the study design of a phase 3 trial of C+N+I vs N+I in previously untreated pts with aRCC of IMDC intermediate or poor risk (NCT03937219). Methods: This randomized, double-blind, controlled phase 3 study evaluates the efficacy and safety of C+N+I vs N+I in previously untreated pts with IMDC intermediate or poor risk aRCC. Eligible pts are randomized 1:1 to receive C+N+I or N+I in combination with placebo, stratified by IMDC prognostic score and geographic region. Pts receive C (40 mg oral QD) + N (3 mg/kg IV Q3W) x 4 doses + I (1 mg/kg IV Q3W) x 4 doses, followed by C (40 mg oral QD) + N (480 mg IV flat dose Q4W). Control pts receive C-matched placebo and the same treatment regimen for N+I as the experimental arm. N will be administered for a maximum of 2 years. Eligibility criteria include histologically confirmed metastatic or aRCC with a clear cell component, intermediate or poor risk RCC per IMDC criteria, measurable disease per RECIST 1.1, KPS ≥70%, adequate organ and marrow function and age ≥18 years. Exclusion criteria include prior systemic therapy for aRCC and uncontrolled significant illnesses. The primary endpoint is PFS per RECIST 1.1 by BICR; the secondary endpoint is OS. Additional endpoints include ORR, safety, correlation of biomarkers with outcomes, and pharmacokinetics of C in combination with N+I. The first patient was enrolled in June 2019 and enrollment is ongoing. Clinical trial information: NCT03937219.

A phase III study of futibatinib (TAS-120) versus gemcitabine-cisplatin (gem-cis) chemotherapy as first-line (1L) treatment for patients (pts) with advanced (adv) cholangiocarcinoma (CCA) harboring fibroblast growth factor receptor 2 (FGFR2) gene rearrangements (FOENIX-CCA3).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS600-TPS600 ◽  
Author(s):  
Mitesh J. Borad ◽  
John A. Bridgewater ◽  
Chigusa Morizane ◽  
Rachna T. Shroff ◽  
Do-Youn Oh ◽  
...  
Keyword(s):  
Disease Progression ◽  
Performance Status ◽  
Objective Response ◽  
Phase Iii ◽  
Clinical Activity ◽  
Gene Rearrangements ◽  
Open Label ◽  
Phase 3 ◽  
Fgfr2 Gene ◽  
Ectopic Mineralization

TPS600 Background: Pts with adv CCA have poor survival outcomes, and chemotherapy offers limited survival benefit (5-year survival rates, 5–10%; median overall survival [OS], 8–12 months). FGFR2 gene rearrangements are known to be early drivers of oncogenesis in ~15% of pts with intrahepatic (i) CCA. Futibatinib, an oral, highly selective, irreversible FGFR1-4 inhibitor has shown antitumor activity against a broad spectrum of FGFR-deregulated tumors in preclinical studies. In a previous study, futibatinib demonstrated clinical activity and tolerability in heavily pretreated pts with adv CCA harboring FGFR2 gene rearrangements. This phase 3 trial (FOENIX-CCA3) is designed to evaluate futibatinib vs gem-cis as 1L therapy for pts with adv iCCA harboring FGFR2 rearrangements. Methods: FOENIX-CCA3 is a multicenter, open-label, randomized phase 3 study that will be conducted in pts with metastatic or unresectable iCCA harboring FGFR2 rearrangements (assessed at screening by a central laboratory). Pts must have an ECOG performance status of 0 or 1 and should not have received previous systemic anticancer therapy for adv disease (adjuvant/neoadjuvant therapy ≥6 mo prior to randomization is permissible). Pts with clinically-significant alterations in calcium-phosphorus homeostasis or ectopic mineralization/calcification will be excluded. Approximately 216 pts will be randomized (1:1 ratio) to receive 20 mg futibatinib once daily until disease progression or other discontinuation criteria are met or gem-cis (on days 1 and 8 of a 21-day cycle) for 8 cycles or until disease progression, whichever occurs first. Pts will be stratified by prior surgical excision (yes vs no), geographic region, and locally adv vs metastatic disease. The primary endpoint is progression-free survival (PFS) assessed by independent central review (ICR). Secondary endpoints include objective response rate and disease control rate based on ICR, OS, PFS per investigator assessment, and safety. The anticipated start date is in April, 2020.

Sign in / Sign up

Export Citation Format

Share Document