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ATIM-28. PHASE 2 STUDY OF ERC1671 PLUS BEVACIZUMAB VS BEVACIZUMAB PLUS PLACEBO IN RECURRENT GBM INTERIM RESULTS AND CORRELATIONS WITH CD4+ T LYMPHOCYTE COUNTS

ABSTRACT: Abstract BACKGROUND ERC1671 is an allogeneic/autologous therapeutic glioblastoma (GBM) vaccine composed of whole, inactivated tumor cells mixed with tumor cell lysates derived from the patient and three GBM donors. Previously published compassionate use data showed an overall survival (OS) of 43 weeks (10 months) in patients with a good performance status. METHODS In this double-blinded, randomized, phase 2 study bevacizumab-naïve patients with recurrent GBM were randomized after surgery to receive either ERC1671 in combination with GM-CSF and cyclophosphamide plus bevacizumab, or placebo plus bevacizumab. The trial is registered with ClinicalTrials.gov (NCT01903330). Interim RESULTS Nine patients, with a KPS 70, were randomized and treated. At the time of further progression, these patients were unblinded, as stipulated by the protocol, which revealed that four had received vaccine, four had received placebo, and one was non-evaluable. Median OS of patients treated with ERC1671 plus bevacizumab was 12 months, with one patient surviving >2 years. In the group treated with placebo plus bevacizumab, median OS was shorter at 7.5 months, with all patients having succumbed within 1 year. Toxicity analysis showed an equal distribution of adverse events (AE) between the vaccine and placebo groups, with no grade 4 or 5 toxicities. The maximal CD4+ T lymphocyte count in the peripheral blood correlated with OS in the ERC1671 but not in the placebo group. CONCLUSIONS The addition of ERC1671/GM-CSF/cyclophosphamide to bevacizumab resulted in a potential survival benefit with minimal additional toxicity. The maximal CD4+ T lymphocyte count in the peripheral blood correlated with OS. The study is ongoing with the addition of two other sites.

SUBMITTER: Bota D

PROVIDER: S-EPMC6216140 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe current study aimed to evaluate the value of immune cell counts and neutrophil-to-lymphocyte ratio (NLR) when attempting to predict 28-day mortality.MethodsWe conducted an observational retrospective study that included consecutive septic patients. Severity scores on the first day and peripheral circulating immune cell counts (at day 1, day 3, day 5 and day 7 of admission) were collected during each patient's emergency intensive care unit stay. We assessed the associations of peripheral circulating immune cell counts and NLR with the severity of illness. The relationships between 28-day mortality and peripheral circulating immune cell counts and NLR with were evaluated using Cox proportional cause-specific hazards models.ResultsA total of 216 patients diagnosed with sepsis caused by IAI were enrolled. The lymphocyte counts (days 1, 3, 5 and 7) and monocyte counts (days 3, 5 and 7) were significantly lower in non-survivors (n = 72) than survivors (n = 144). The NLR values at each time point were significantly higher in non-survivors. The day 1 lymphocyte counts, as well as the monocyte counts, were significantly lower in the highest-scoring group, when stratified by the Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores, than in the other groups (p < 0.05). The day 1 NLR was significantly higher in the highest-scoring group than in the other groups (p < 0.05). The day 5 and day 7 lymphocyte counts, day 3 and day 7 monocyte counts and day 7 NLR were significant predictors of 28-day mortality in the Cox proportional hazards models (day 5 lymphocyte count: hazard ratio, 0.123 (95% CI, 0.055-0.279), p < 0.001; day 7 lymphocyte count: hazard ratio, 0.115 (95% CI, 0.052-0.254), p < 0.001; day 3 monocyte count: hazard ratio, 0.067 (95% CI, 0.005-0.861), p = 0.038; day 7 monocyte count: hazard ratio, 0.015 (95% CI, 0.001-0.158), p < 0.001; day 7 NLR: hazard ratio, 0.773 (95% CI, 0.659-0.905), p = 0.001).ConclusionsThe results showed that circulating lymphocytes and monocytes were dramatically decreased within 7 days in non-survivors following sepsis from an IAI. Lymphocyte counts, monocyte counts and NLR appeared to be associated with the severity of illness, and they may serve as independent predictors of 28-day mortality in septic patients with IAIs.

Project description:Tenofovir (TDF) with emtricitabine (FTC) and zidovudine (ZDV) is a recognized alternate first-line antiretroviral (ART) regimen for patients who cannot start treatment with non-nucleoside reverse transcriptase inhibitors (NNRTIs). Clinical studies comparing TDF+FTC+ZDV to other regimens are lacking.Participants in a trial of early ART in Côte d'Ivoire (Temprano ANRS 12136) started treatment with TDF/FTC plus either efavirenz (EFV) or ZDV (HIV-1+2 dually infected patients and women refusing contraception or previously treated with nevirapine). We compared rates of upper digestive serious adverse events (sAEs) between TDF/FTC+EFV and TDF/FTC+ZDV patients during the first six months of treatment. sAEs were defined as either grade 3-4 AEs or persistent grade 1-2 AEs leading to drug discontinuation.A total of 197 patients (76% women, median CD4 count 395/mm(3)) started therapy with TDF/FTC, 126 with EFV and 71 with ZDV. During the first six months of ART, 94 patients had digestive AEs (nausea/vomiting) of any grade (EFV 36/126, 29%; ZDV 58/71, 82%, p<0.0001), including 20 sAEs (EFV 3/126, 5%; ZDV 17/71, 24%, p<0.0001). In-patients on TDF/FTC+ZDV with digestive AEs, the median time to the first symptom was two days (IQR: 1-4). Plasma ZDV (Cmax) distributions and pill ZDV dosages were normal. Patients with digestive AEs had higher haemoglobin levels and tended to have higher body mass indices and more frequent past histories of cotrimoxazole (CTX) prophylaxis.We observed an unexpectedly high rate of digestive sAEs in West African adults, mostly women, who started a 3-nuc ART with TDF/FTC+ZDV in Côte d'Ivoire. These adults were participating in a trial of early ART and had much higher CD4 counts than those who currently routinely start ART in sub-Saharan Africa. They all received CTX concomitantly with ZDV. We suggest that further early prescriptions of TDF+XTC+ZDV should be carefully monitored and that whenever possible, the rate of early upper digestive adverse events should be compared to that occurring in-patients taking other drug regimens.NCT00495651.

Project description:BackgroundHIV/AIDS is a chronic disease leading to complications in infected individuals that often require surgical intervention. These patients' serum CD4 T lymphocyte (CD4) counts represent one of the most important indicators of their ability to tolerate surgical treatment. Previous studies have demonstrated that CD4 cell count (CD4-CC) < 200 cells/μl may increase the risk of surgical complications in these patients, limiting their ability to undergo surgery, which may negatively affect their quality of life. Further investigation into the surgical outcomes of patients with CD4-CC < 200 cells/μl should provide guidance in making appropriate clinical decisions for the optimal healthcare of this patient demographic.MethodsAll enrolled patients were selected from 14 prefecture-level general hospitals in Guangxi, China, and were referred to AIDS outpost hospitals for inpatient surgical therapy. A total cohort of 168 adult patients was retrospectively analyzed. Multifactorial and stratified analyses were performed to evaluate the in surgical outcome differences for patients with CD4-CC < 200 cells/μl (N = 43), using those with CD4-CC ≥ 200 cells/μl (N = 125) as controls.ResultsPoor incisional healing was used as the primary outcome indicator, and postoperative complications were used as the secondary outcome indicator. In the patient group with CD4-CC < 200 cells/μl, the risk of surgical complications was significantly increased (OR 2.379; 95% CI [1.049-5.394]) after adjustment. Adjusted stratified analysis of the CD4-CC < 200 cells/μl group revealed that individuals over 60 years (OR 27.504; 95% CI [2.297-329.317]) with erythrocyte counts below 4.00/ml for males or 3.50/ml for females (OR 3.353; 95% CI [1.079-10.419]) had a significantly higher risk of postoperative complications; this finding was statistically different from the control (CD4 ≥ 200 cells/μl) group. However, there was no significant difference between the two groups regarding the risk of poorly healed incision outcomes.ConclusionsPreliminary findings suggest that a serum CD4-CC < 200 cells/μl is not a definitive contraindication for surgical therapy and that baseline and surgical characteristics may help predict surgical outcomes in these patients. Further studies are needed to confirm these findings.

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ATIM-28. PHASE 2 STUDY OF ERC1671 PLUS BEVACIZUMAB VS BEVACIZUMAB PLUS PLACEBO IN RECURRENT GBM INTERIM RESULTS AND CORRELATIONS WITH CD4+ T LYMPHOCYTE COUNTS

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