scholarly journals 542 Randomized trial of tumor lysate particle only vaccine vs. tumor lysate particle-loaded, dendritic cell vaccine to prevent recurrence of resected stage III/IV melanoma: 36-month analysis

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A571-A571
Author(s):  
Elizabth Carpenter ◽  
Lexy Adams ◽  
Robert Chick ◽  
Guy Clifton ◽  
Timothy Vreeland ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Dendritic Cell ◽  
Adverse Events ◽  
Stage Iii ◽  
Phase 2 ◽  
Tumor Lysate ◽  
Phase 2 Trial ◽  
Kaplan Meier ◽  
Resected Stage ◽  
To Receive

BackgroundThe tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is an autologous tumor vaccine that decreased recurrence in stage III/IV melanoma when granulocyte-colony stimulating factor (G-CSF) was not used to harvest the dendritic cells in a randomized phase 2B adjuvant trial.1The tumor lysate (TL) particle only (TLPO) vaccine utilizes a similar mechanism, but with autologous TL-loaded yeast cell wall particles; this eliminates the need for dendritic cell (DC) collection and ex-vivo loading and reduces production costs and time. The TLPO vaccine was compared to TLPLDC in an embedded bridging portion of the trial. Here, we examine 36-month outcomes of the ongoing randomized, double-blind phase 2 trial in patients (pts) with resected stage III/IV melanoma.MethodsPts were randomized 2:1 to receive TLPO or TLPLDC as a continuation of a previously established clinical trial comparing TLPLDC versus placebo. The TLPLDC group was analyzed separately based on use (or not) of G-CSF for collection of DC. Safety was measured by the Common Terminology Criteria for Adverse Events (CTCAE). Kaplan-Meier and log-rank analysis was used to compare 36-month disease-free survival (DFS) and overall survival (OS) in the intention-to-treat (ITT) main arms as well as pre-specified subgroups.ResultsA total of 187 pts were randomized with 41, 47, 56, and 43 pts enrolled in the placebo, TLPLDC without G-CSF (TLPLDC), TLPLDC with G-CSF (TLPLDC+G), and TLPO arm, respectively. Pts randomized to the TLPO arm were more likely to have stage IV melanoma (22.0% for placebo, 20.4% for TLPLDC and TLPLDC+G, and 44.2% for TLPO; p = 0.002) and to receive prior immunotherapy (36.6% for placebo, 39.8% for both TLPLDC and TLPLDC+G, and 83.7% for TLPO; p < 0.001). Grade 3+ adverse events were not significantly different between arms. In the ITT analysis, 36-month DFS was 30.0% for placebo, 55.8% for TLPLDC, 24.4% for TLPLDC+G, and 64.0% for TLPO (p < 0.001). OS at 36 months was 70.9% for placebo, 94.2% for TLPLDC, 69.8%% for TLPLDC+G, and 94.8% for TLPO (p = 0.011) (figure 1).Abstract 542 Figure 1Kaplan-Meier curves demonstrating DFS (A) and OS (B) between Placebo (n=41), TLPLDC (n=47), TLPLDC+G (n=56), and TLPO (n=43)ConclusionsThe TLPO and TLPLDC (without G-CSF) vaccines improved 36-month DFS and OS in this randomized phase 2 trial. The efficacy of the TLPO and TLPLDC vaccines will be confirmed in a phase III trial in resected Stage III/IV melanoma pts.Trial RegistrationNIH, clinicaltrials.gov, NCT02301611ReferencesO’Shea AE, Chick RC, Clifton GT, et al. The effect of pretreatment with G-CSF prior to dendritic cell collection during the phase IIb trial of an autologous DC-based vaccine for advanced, resectable melanoma. Presented at: Society for Immunotherapy of Cancer 35th Anniversary Annual Meeting & Preconference Programs (SITC 2020); November 11–14, 2020. Abstract 310. J Immunother Cancer. 2020;8(Suppl 3):A656–A959.Ethics ApprovalThe clinical trial protocol was approved by the Western Institutional Review Board (2014–1932). All participants provided informed consent prior to enrollment in the trial.

scholarly journals 431 Prospective, randomized trial of the tumor lysate, particle only vaccine compared to the tumor lysate, particle-loaded, dendritic cell vaccine to prevent recurrence for resected stage III/IV melanoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A456-A457
Author(s):  
Patrick McCarthy ◽  
Lexy Adams ◽  
Robert Chick ◽  
Guy Clifton ◽  
Timothy Vreeland ◽  
...  
Keyword(s):  
Overall Survival ◽  
Dendritic Cell ◽  
Ex Vivo ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Tumor Lysate ◽  
Free Survival ◽  
Resected Stage ◽  
Disease Free

BackgroundThe autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is safe and effective in improving 24 and 36-month disease-free survival (DFS) in patients (pts) with resected stage III/IV melanoma who completed the primary vaccine series. The tumor lysate, particle only (TLPO) vaccine has been developed to accelerate production by omitting DC isolation and ex vivo loading in favor of in vivo phagocytosis of the TL-loaded particles. We are currently conducting a randomized and double-blind trial of the TLPO vs TLPLDC to improve DFS and overall survival (OS) in patients with resected late stage melanoma.MethodsPatients with stage III/IV melanoma who were clinically disease-free after standard of care therapies were randomized to receive TLPO vs TLPLDC (2:1) as a continuation of the phase IIb trial comparing TLPLDC vs placebo (2:1). For the TLPLDC vaccine, autologous TL was loaded into yeast cell wall particles (YCWP) which were then phagocytized by isolated autologous DC ex vivo. For the placebo DC were loaded with empty YCWP. For TLPO, the autologous TL-loaded YCWP were coated with a chemoattractant and injected intradermally for in vivo phagocytosis. Some patients in the TLPLDC arm received G-CSF prior to DC harvest to minimize blood draw (60 mL instead of 120 mL without G-CSF). For all arms, six vaccine/placebo doses were administered intradermally at 0, 1, 2, 6, 12, and 18 mos. Data was analyzed by an intention-to-treat (ITT) analysis for DFS and OS by the Kaplan-Meier method and compared by log-rank test.Results63 pts were randomized to TLPO (n=43) vs TLPLDC (n=20). The TLPO cohort contained more females and received less chemotherapy (0% vs 10%), but otherwise were comparable. There were no differences in DFS (p=0.948) or OS (p=0.779) between the two vaccines (figures 1&2). Comparing the TLPO pts to all other pts in the phase IIb trial [TLPLDC+G-CSF (n=57), TLPLDC-G-CSF (n=46), and placebo (n=41)] the TLPO arm had improved DFS compared to placebo (p=0.019) and TLPLDC+G-CSF (p=0.001), but roughly equivalent to the TLPLDC-G-CSF arm (p=0.276) (figure 3). A similar trend was seen in OS analysis, though differences were not statistically significant (figure 4).Abstract 431 Figure 1TLPO vs TLPLDC (n=20) DFS. Disease-free survival of TLPO patients compared to similar TLPLDC patients (n=20)Abstract 431 Figure 2TLPO vs TLPLDC (n=20) OS. Overall survival of TLPO patients compared to similar TLPLDC patients (n=20)Abstract 431 Figure 3TLPO vs TLPLDC subsets vs Placebo DFS. Disease-free survival of TLPO patients compared to placebo and all TLPLDC patients (n=103) stratified by use of G-CSFAbstract 431 Figure 4TLPO vs TLPLDC subsets vs Placebo OS. Disease-free survival of TLPO patients compared to placebo and all TLPLDC patients (n=103) stratified by use of G-CSFConclusionsTLPO and TLPLDC vaccines (without the use of G-CSF) improve DFS in patients with resected stage III/IV melanoma compared to placebo. The TLPO vaccine may offer advantages via reduced cost and vaccine production time. TLPO should be closely considered for further clinical trials.Trial RegistrationNCT02301611: Phase IIB TL + YWCP + DC in MelanomaTLPLDC IND#16101TLPO IND#17274Ethics ApprovalThis study was approved by WIRB; protocol #20141932

scholarly journals Plant Formulation ATRICOV 452 in Improving the Level of COVID-19 Specific Inflammatory Markers in Patients

2021 ◽  
Author(s):  
Latha Damle ◽  
Hrishikesh Damle ◽  
Bharath BR
Keyword(s):  
Health Care ◽  
Clinical Trial ◽  
Inflammatory Markers ◽  
Phase 1 ◽  
Health Care Facilities ◽  
Phase 2 ◽  
Primary Analysis ◽  
Phase 2 Trial ◽  
Organ Systems ◽  
To Receive

Due to the huge demand for health care facilities, there is a need for safe therapeutic intervention which can reduce the need for extensive health care support. In that regard, the current study was aimed at performing Phase 1 clinical trial to determine the safety of plant formulation in 24 healthy volunteers and Phase 2 trials in 100 COVID-19 patients to determine the tolerability and impact on the level of COVID 19 specific inflammatory markers. The outcomes of the Phase 1study have suggested the safe usage of plant formulation in humans and encouraged to conduct Phase 2 clinical trial. In the Phase 2 trial, the plant formulation was evaluated in 100 COVID-19 patients along with the standard of care. In Phase 1 single dose of 500 mg plant formulation capsule was used as an intervention, while 1gm thrice a day of plant formulation for 14 days was the testing dose for Phase 2. During the Phase 1 trial, no adverse event was observed and all organ systems were normal in function. During the Phase 2 trial, 100 patients underwent randomization, 50 were assigned to receive plant formulation, and 50 to receive placebo. Three patients in the placebo and two patients in the plant formulation group had dropped out from the study. Hence, the primary analysis population included 95 patients (48 allocated to plant formulation and 47 to placebo). The COVID 19 specific inflammatory markers improved faster and became normal in the plant formulation treatment group. In conclusion, the plant formulation (ATRICOV 452) has been found to be safe in phases 1 and 2.

scholarly journals 300 Final analysis of a prospective, randomized, double-blind, placebo-controlled phase IIb trial of tumor lysate, particle-loaded, dendritic cell vaccine in stage III/IV melanoma: 36-month analysis

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A327-A327
Author(s):  
Lexy Adams ◽  
Robert Chick ◽  
Guy Clifton ◽  
Timothy Vreeland ◽  
Patrick McCarthy ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Stage Iv ◽  
Standard Of Care ◽  
Stage Iii ◽  
Tumor Lysate ◽  
Double Blind ◽  
Free Survival ◽  
Resected Stage ◽  
Disease Free ◽  
Stage Iv Melanoma

BackgroundThe tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is created ex vivo by loading autologous dendritic cells (DC) with yeast cell wall particles (YCWP) containing autologous tumor lysate, thus delivering tumor antigens to the DC cytoplasm via phagocytosis. TLPLDC then activates a robust T cell response against the unique antigens for each patient. The primary analysis of the prospective, randomized, multi-center, double-blind, placebo-controlled phase IIb trial in patients with resected stage III/IV melanoma showed TLPLDC improved 24-month disease-free survival (DFS) in the per-treatment (PT) analysis (patients completing the 6-month primary vaccine series). Here, we examine the secondary endpoint of 36-month DFS and overall survival (OS).MethodsPatients with resected stage III/IV melanoma were randomized 2:1 to TLPLDC vaccine or placebo (autologous DC loaded with empty YCWP). Treatments were given at 0, 1, 2, 6, 12 and 18 months. The protocol was amended to include patients receiving concurrent checkpoint inhibitors (CPIs) to follow changes in standard of care. The co-primary endpoints were 24-month DFS by intention-to-treat (IT) analysis and per-treatment (PT) analysis, with secondary endpoints including 36-month DFS and OS by ITT and PT analysis, pre-specified analysis by stage, and safety as measured by CTCAE v4.03.ResultsOverall, 103 patients received TLPLDC and 41 placebo. In PT analysis, 65 patients received TLPLDC and 32 placebo. Total adverse events (AEs), grade 3+ AEs, and serious AEs (SAEs) were similar in placebo vs TLPLDC groups, with one related SAE per treatment arm. By ITT analysis, 36-month OS was 76.2% for TLPLDC vs 70.3% for placebo (HR 0.72, p=0.437) and 36-month DFS was 35.6% vs 27.1% (HR 0.95, p=0.841). By PT analysis, 36-month DFS was improved with TLPLDC (57.5% vs 35.0%; HR 0.50, p=0.025, figure 1). This effect was even more dramatic in resected stage IV patients (36-month DFS: 60.9% vs 0%; HR 0.12, p=0.001, figure 2).ConclusionsThis phase IIb trial again demonstrates the safety of the TLPLDC vaccine, and an improved 36-month DFS in patients with resected stage III/IV melanoma who complete the primary vaccine series, particularly in the stage IV subgroup. Next, a phase III trial will evaluate the efficacy of TLPLDC vaccine as adjuvant treatment for resected stage IV melanoma, with patients randomized to receive standard of care PD-1 inhibitors + TLPLDC versus PD-1 inhibitors + placebo.Abstract 300 Figure 136-month disease free survival for patients receiving TLPLDC vs placebo by PT analysisAbstract 300 Figure 236-month disease free survival for subset of stage IV melanoma patients receiving TLPLDC vs placebo by PT analysisTrial RegistrationThis is a phase IIb clinical trial registered under NCT02301611Ethics ApprovalThis study was approved by Western IRB, protocol 20141932.

scholarly journals Completely resected stage III melanoma controversy - 15 years of national tertiary centre experience

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Barbara Peric ◽  
Sara Milicevic ◽  
Andraz Perhavec ◽  
Marko Hocevar ◽  
Janez Zgajnar
Keyword(s):  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Rapid Development ◽  
Primary Tumour ◽  
Stage Iii ◽  
Unknown Primary ◽  
Tertiary Centre ◽  
Kaplan Meier ◽  
Stage Iii Melanoma ◽  
Resected Stage

AbstractBackgroundTwo prospective randomized studies analysing cutaneous melanoma (CM) patients with sentinel lymph node (SLN) metastases and rapid development of systemic adjuvant therapy have changed our approach to stage III CM treatment. The aim of this study was to compare results of retrospective survival analysis of stage III CM patients’ treatment from Slovenian national CM register to leading international clinical guidelines.Patients and methodsSince 2000, all Slovenian CM patients with primary tumour ≥ TIb are treated at the Institute of Oncology Ljubljana and data are prospectively collected into a national CM registry. A retrospective analysis of 2426 sentinel lymph node (SLN) biopsies and 789 lymphadenectomies performed until 2015 was conducted using Kaplan-Meier survival curves and log-rank tests.ResultsPositive SLN was found in 519/2426 (21.4%) of patients and completion dissection (CLND) was performed in 455 patients. The 5-year overall survival (OS) of CLND group was 58% vs. 47% of metachronous metastases group (MLNM) (p = 0.003). The 5-year OS of patients with lymph node (LN) metastases and unknown primary site (UPM) was 45% vs. 21% of patients with synchronous LN metastasis. Patients with SLN tumour burden < 0.3 mm had 5-year OS similar to SLN negative patients (86% vs. 85%; p = 0.926). The 5-year OS of patients with burden > 1.0 mm was similar to the MLNM group (49% vs. 47%; p = 0.280).ConclusionsStage III melanoma patients is a heterogeneous group with significant OS differences. CLND after positive SLNB might still remain a method of treatment for selected patients with stage III.

scholarly journals ATIM-13. ALLOGENEIC TUMOR LYSATE/AUTOLOGOUS DENDRITIC CELL VACCINES IN NEWLY DIAGNOSED GLIOBLASTOMA: RESULTS OF CLINICAL TRIAL MC1272

2017 ◽  
Vol 19 (suppl_6) ◽  
pp. vi28-vi29 ◽  
Author(s):  
Ian F Parney ◽  
Michael P Gustafson ◽  
Timothy Peterson ◽  
Susan M Steinmetz ◽  
Allan B Dietz
Keyword(s):  
Clinical Trial ◽  
Dendritic Cell ◽  
Newly Diagnosed ◽  
Autologous Dendritic Cell ◽  
Tumor Lysate ◽  
Allogeneic Tumor ◽  
Dendritic Cell Vaccines ◽  
Newly Diagnosed Glioblastoma

Randomized Clinical Trial of Adjuvant Mitomycin Plus Tegafur in Patients With Resected Stage III Gastric Cancer

1999 ◽  
Vol 17 (12) ◽  
pp. 3810-3815 ◽  
Author(s):  
Lluís Cirera ◽  
Anna Balil ◽  
Eduard Batiste-Alentorn ◽  
Ignasi Tusquets ◽  
Teresa Cardona ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinical Trial ◽  
Overall Survival ◽  
Survival Rate ◽  
Adjuvant Chemotherapy ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Free Survival ◽  
Resected Stage ◽  
Disease Free

PURPOSE: The efficacy of adjuvant chemotherapy in gastric cancer is controversial. We conducted a phase III, randomized, multicentric clinical trial with the goal of assessing the efficacy of the combination of mitomycin plus tegafur in prolonging the disease-free survival and overall survival of patients with resected stage III gastric cancer. PATIENTS AND METHODS: Patients with resected stage III gastric adenocarcinoma were randomly assigned, using sealed envelopes, to receive either chemotherapy or no further treatment. Chemotherapy was started within 28 days after surgery according to the following schedule: mitomycin 20 mg/m2 intravenously (bolus) at day 1 of chemotherapy; 30 days later, oral tegafur at 400 mg bid daily for 3 months. Disease-free survival and overall survival were estimated using the Kaplan-Meier analysis and the Cox proportional hazards model. RESULTS: Between January 1988 and September 1994, 148 patients from 10 hospitals in Catalonia, Spain, were included in the study. The median follow-up period was 37 months. The tolerability of the treatment was excellent. The overall survival and disease-free survival were higher in the group of patients treated with chemotherapy (P = .04 for survival and P = .01 for disease-free survival in the log-rank test). The overall 5-year survival rate and the 5-year disease-free survival rate were, respectively, 56% and 51% in the treatment group and 36% and 31% in the control group. CONCLUSION: Our positive results are consistent with the results of recent studies; which conclude that there is a potential benefit from adjuvant chemotherapy in resected gastric cancer.

scholarly journals Immune-related Adverse Events of Dendritic Cell Vaccination Correlate With Immunologic and Clinical Outcome in Stage III and IV Melanoma Patients

2016 ◽  
Vol 39 (6) ◽  
pp. 241-248 ◽  
Author(s):  
Steve Boudewijns ◽  
Harm Westdorp ◽  
Rutger H.T. Koornstra ◽  
Erik H.J.G. Aarntzen ◽  
Gerty Schreibelt ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Clinical Outcome ◽  
Adverse Events ◽  
Stage Iii ◽  
Dendritic Cell Vaccination ◽  
Melanoma Patients

Updated Survival Analyses after Prolonged Follow-Up of the Phase 2, Multicenter CREST Study of Bortezomib in Relapsed or Refractory Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2717-2717 ◽  
Author(s):  
Sundar Jagannath ◽  
Bart Barlogie ◽  
James R. Berenson ◽  
David Siegel ◽  
D. Irwin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase 2 ◽  
Initial Report ◽  
Refractory Multiple Myeloma ◽  
Kaplan Meier ◽  
Phase 2 Study ◽  
The Difference ◽  
Dose Levels ◽  
To Receive

Abstract Background: The initial report of the CREST phase 2 study (Br J Haematol2004;127:165–72) demonstrated the substantial activity of bortezomib (VELCADE®, Vc) at two different dose levels in patients with relapsed or refractory multiple myeloma (MM). Here, we provide an updated analysis of overall survival (OS) after prolonged follow-up (median >5 years). Methods: 54 patients were enrolled to receive Vc 1.0 mg/m2 (n=28) or 1.3 mg/m2 (n=26) on days 1, 4, 8, and 11 of a 21-day cycle, for up to 8 cycles. Dexamethasone (dex) 20 mg on the day of and day after each Vc dose was added for 16 (57%) patients in the 1.0 mg/m2 group and 12 (46%) patients in the 1.3 mg/m2 group, upon suboptimal response to Vc alone. A total of 17 (31%) patients continued to receive Vc ± dex in an extension study, 12 (43%) from the 1.0 mg/m2 and 5 (19%) from the 1.3 mg/m2 groups. Patients received a median of 3 (range, 1–7) prior regimens. Median time from diagnosis to first Vc dose was 2 years. In the 1.0 and 1.3 mg/m2 groups, respectively, mean age was 64 vs 60 years, 50% vs 35% of patients were male, 54% vs 65% had IgG MM, 58% vs 48% had β2-microglobulin ≥4 mg/L, and 29% vs 48% had abnormal cytogenetics. Response rate (CR+PR, EBMT criteria) to Vc alone was 30% vs 38%, and to Vc ± dex was 37% vs 50% in the 1.0 and 1.3 mg/m2 groups. OS from first dose of Vc in each dose group was analyzed using the Kaplan-Meier method. Results: Median OS in the 1.0 and 1.3 mg/m2 groups was 26.8 months and 60.0 months, after median follow-up of 61 and 65 months, respectively (Figure). In the 1.0 mg/m2 group, 21 (75%) patients have died; the 1- and 2-year OS rates were 82% and 54%, respectively. In the 1.3 mg/m2 group, only 14/26 (54%) patients have died; 1- and 2-year OS rates were 81% and 69%, respectively. Conclusions: Vc ± dex was active in relapsed or refractory MM at both the 1.0 mg/m2 and 1.3 mg/m2 dose levels and was associated with notable OS, particularly in patients treated with the approved Vc dose of 1.3 mg/m2. The difference in OS between dose groups suggests that the higher dose of Vc is more active. Figure. Kaplan-Meier analyses of OS in patients who received Vc 1.0 mg/m2 (n=28) or 1.3 mg/m2 (n=26). Figure Figure

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