JULIANA PEREIRA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
14 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 14
- Association between bortezomib dose intensity and overall survival in mantle cell lymphoma patients on frontline VR-CAP in the phase 3 LYM-3002 study(*)(2019) ROBAK, Tadeusz; HUANG, Huiqiang; JIN, Jie; ZHU, Jun; LIU, Ting; SAMOILOVA, Olga; PYLYPENKO, Halyna; VERHOEF, Gregor; SIRITANARATKUL, Noppadol; OSMANOV, Evgenii; PEREIRA, Juliana; MAYER, Jiri; HONG, Xiaonan; OKAMOTO, Rumiko; PEI, Lixia; ROONEY, Brendan; VELDE, Helgi van de; CAVALLI, FrancoThe pivotal LYM-3002 study compared frontline rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) with bortezomib, rituximab, cyclophosphamide, doxorubicin and prednisone (VR-CAP) in newly diagnosed mantle cell lymphoma (MCL) patients for whom stem cell transplantation was not an option. This post hoc subanalysis of the VR-CAP data from LYM-3002 evaluated the effect of bortezomib dose intensity on OS in patients who completed >= 6 cycles of treatment. From the end of cycle 6, patients receiving >= 4.6 mg/m(2)/cycle of bortezomib had significantly longer OS (but not PFS) compared with those receiving <4.6 mg/m(2)/cycle by univariate analysis (HR 0.43 [95% CI: 0.23-0.80]; p = .0059). This association remained significant in multivariate analysis adjusting for baseline patient and disease characteristics (HR 0.40 [95% CI: 0.20-0.79]; p = .008]. Higher bortezomib dose intensity was the strongest predictor of OS in newly diagnosed MCL patients receiving VR-CAP. Clinicaltrials.gov identifier: NCT00722137.
- Bortezomib-Based Therapy for Newly Diagnosed Mantle-Cell Lymphoma(2015) ROBAK, Tadeusz; HUANG, Huiqiang; JIN, Jie; ZHU, Jun; LIU, Ting; SAMOILOVA, Olga; PYLYPENKO, Halyna; VERHOEF, Gregor; SIRITANARATKUL, Noppadol; OSMANOV, Evgenii; ALEXEEVA, Julia; PEREIRA, Juliana; DRACH, Johannes; MAYER, Jiri; HONG, Xiaonan; OKAMOTO, Rumiko; PEI, Lixia; ROONEY, Brendan; VELDE, Helgi van de; CAVALLI, FrancoBACKGROUND The proteasome inhibitor bortezomib was initially approved for the treatment of relapsed mantle-cell lymphoma. We investigated whether substituting bortezomib for vincristine in frontline therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) could improve outcomes in patients with newly diagnosed mantle-cell lymphoma. METHODS In this phase 3 trial, we randomly assigned 487 adults with newly diagnosed mantle-cell lymphoma who were ineligible or not considered for stem-cell transplantation to receive six to eight 21-day cycles of R-CHOP intravenously on day 1 (with prednisone administered orally on days 1 to 5) or VR-CAP (R-CHOP regimen, but replacing vincristine with bortezomib at a dose of 1.3 mg per square meter of body-surface area on days 1, 4, 8, and 11). The primary end point was progression-free survival. RESULTS After a median follow-up of 40 months, median progression-free survival (according to independent radiologic review) was 14.4 months in the R-CHOP group versus 24.7 months in the VR-CAP group (hazard ratio favoring the VR-CAP group, 0.63; P<0.001), a relative improvement of 59%. On the basis of investigator assessment, the median durations of progression-free survival were 16.1 months and 30.7 months, respectively (hazard ratio, 0.51; P<0.001), a relative improvement of 96%. Secondary end points were consistently improved in the VR-CAP group, including the complete response rate (42% vs. 53%), the median duration of complete response (18.0 months vs. 42.1 months), the median treatment-free interval (20.5 months vs. 40.6 months), and the 4-year overall survival rate (54% vs. 64%). Rates of neutropenia and thrombocytopenia were higher in the VR-CAP group. CONCLUSIONS VR-CAP was more effective than R-CHOP in patients with newly diagnosed mantle-cell lymphoma but at the cost of increased hematologic toxicity. (Funded by Janssen Research and Development and Millennium Pharmaceuticals; LYM-3002 ClinicalTrials.gov number, NCT00722137.)
- Mogamulizumab versus investigator's choice of chemotherapy regimen in relapsed/refractory adult T-cell leukemia/lymphoma(2019) PHILLIPS, Adrienne A.; FIELDS, Paul A.; HERMINE, Olivier; RAMOS, Juan C.; BELTRAN, Brady E.; PEREIRA, Juliana; WANDROO, Farooq; FELDMAN, Tatyana; TAYLOR, Graham P.; SAWAS, Ahmed; HUMPHREY, Jeffrey; KURMAN, Michael; MORIYA, Junji; DWYER, Karen; LEONI, Mollie; CONLON, Kevin; COOK, Lucy; GONSKY, Jason; HORWITZ, Steven M.Mogamulizumab, a humanized defucosylated anti-C-C chemokine receptor 4 monoclonal antibody, has been approved in Japan for the treatment of C-C chemokine receptor 4-positive adult T-cell leukemia/lymphoma (ATL). This phase II study evaluated efficacy and safety of mogamulizumab in ATL patients with acute, lymphoma, and chronic subtypes with relapsed/refractory, aggressive disease in the US, Europe, and Latin America. With stratification by subtype, patients were randomized 2: 1 to intravenous mogamulizumab 1.0 mg/kg once weekly for 4 weeks and biweekly thereafter (n=47) or investigator's choice of chemotherapy (n=24). The primary end point was confirmed overall response rate (cORR) confirmed on a subsequent assessment at 8 weeks by blinded independent review. ORR was 11% (95% CI: 4-23%) and 0% (95% CI: 0-14%) in the mogamulizumab and chemotherapy arms, respectively. Best response was 28% and 8% in the respective arms. The observed hazard ratio for progression-free survival was 0.71 (95% CI: 0.41-1.21) and, after post hoc adjustment for performance status imbalance, 0.57 (95% CI: 0.337-0.983). The most frequent treatment-related adverse (grade >= 3) events with mogamulizumab were infusion-related reaction and thrombocytopenia (each 9%). Relapsed/refractory ATL is an aggressive, poor prognosis disease with a high unmet need. Investigator's choice chemotherapy did not result in tumor response in this trial; however, mogamulizumab treatment resulted in 11% cORR, with a tolerable safety profile.
- Randomized Phase III Study of Alisertib or Investigator's Choice (Selected Single Agent) in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma(2019) O'CONNOR, Owen A.; OZCAN, Muhit; JACOBSEN, Eric D.; RONCERO, Josep M.; TROTMAN, Judith; DEMETER, Judit; MASSZI, Tamas; PEREIRA, Juliana; RAMCHANDREN, Radhakrishnan; BEAVEN, Anne; CABALLERO, Dolores; HORWITZ, Steven M.; LENNARD, Anne; TURGUT, Mehmet; HAMERSCHLAK, Nelson; D'AMORE, Francesco A.; FOSS, Francine; KIM, Won-Seog; LEONARD, John P.; ZINZANI, Pier Luigi; CHIATTONE, Carlos S.; HSI, Eric D.; TRUEMPER, Lorenz; LIU, Hua; SHELDON-WANIGA, Emily; ULLMANN, Claudio Dansky; VENKATAKRISHNAN, Karthik; LEONARD, E. Jane; SHUSTOV, Andrei R.PURPOSEThe aim of this open-label, first-in-setting, randomized phase III trial was to evaluate the efficacy of alisertib, an investigational Aurora A kinase inhibitor, in patients with relapsed/refractory peripheral T-cell lymphoma (PTCL).PATIENTS AND METHODSAdult patients with relapsed/refractory PTCLone or more prior therapywere randomly assigned 1:1 to receive oral alisertib 50 mg two times per day (days 1 to 7; 21-day cycle) or investigator-selected single-agent comparator, including intravenous pralatrexate 30 mg/m(2) (once per week for 6 weeks; 7-week cycle), or intravenous gemcitabine 1,000 mg/m(2) or intravenous romidepsin 14 mg/m(2) (days 1, 8, and 15; 28-day cycle). Tumor tissue (disease subtype) and imaging were assessed by independent central review. Primary outcomes were overall response rate and progression-free survival (PFS). Two interim analyses and one final analysis were planned.RESULTSBetween May 2012 and October 2014, 271 patients were randomly assigned (alisertib, n = 138; comparator, n = 133). Enrollment was stopped early on the recommendation of the independent data monitoring committee as a result of the low probability of alisertib achieving PFS superiority with full enrollment. Centrally assessed overall response rate was 33% for alisertib and 45% for the comparator arm (odds ratio, 0.60; 95% CI, 0.33 to 1.08). Median PFS was 115 days for alisertib and 104 days for the comparator arm (hazard ratio, 0.87; 95% CI, 0.637 to 1.178). The most common adverse events were anemia (53% of alisertib-treated patients v 34% of comparator-treated patients) and neutropenia (47% v 31%, respectively). A lower percentage of patients who received alisertib (9%) compared with the comparator (14%) experienced events that led to study drug discontinuation. Of 26 on-study deaths, five were considered treatment related (alisertib, n = 3 of 11; comparator, n = 2 of 15). Two-year overall survival was 35% for each arm.CONCLUSIONIn patients with relapsed/refractory PTCL, alisertib was not statistically significantly superior to the comparator arm.
conferenceObject Final Results of the BP22333 Study Demonstrate Non-Inferior Pharmacokinetics (PK) and Safety of Subcutaneous (SC) Administration of Rituximab Compared with Intravenous (IV) Administration As Maintenance Therapy in Patients with Follicular Lymphoma (FL)(2012) SALAR, Antonio; AVIVI, Irit; LAROUCHE, Jean-Francois; JANIKOVA, Andrea; PEREIRA, Juliana; BREWSTER, Mike; CATALANI, Olivier; MCINTYRE, Christine; SAYYED, Pakeeza; HAYNES, AndrewRituximab has proven efficacy and tolerability for treating B-cell malignancies. IV rituximab administration can take several hours, consuming considerable healthcare resources. A SC rituximab formulation has been developed which may shorten administration time, increase patient (pt) convenience, and potentially reduce IV administration-associated costs. Rituximab efficacy depends on CD20 binding, and Ctrough rituximab levels reflect rituximab exposure throughout the therapy cycle; therefore, achieving a non-inferior Ctrough level with SC dosing is expected to provide comparable efficacy to IV dosing. BP22333 (NCT00930514) is a two-stage phase Ib study assessing PK and tolerability of SC vs IV maintenance rituximab in pts with first-line or relapsed FL. Stage 1 dose-finding results (Salar et al, ASH 2010, abstract 2858; Salar et al, EHA 2012, abstract 0794) identified a fixed dose of 1400 mg for formal Ctrough non-inferiority testing in Stage 2. We report Stage 2 data. The Stage 2 objective was to demonstrate non-inferiority of simulated Ctrough of rituximab SC and IV, using a non-inferiority test with a lower boundary of 0.8 for the 90% confidence interval (CI). Secondary endpoints include SC vs IV rituximab safety and area under the serum concentration-time curve. Eligible pts (N = 157) were aged ≥18 years with an ECOG performance status of ≤ 2, and histologically confirmed CD20-positive grade 1, 2, or 3a FL requiring treatment. Eligible pts must have achieved a complete or partial response following IV rituximab-based induction therapy for FL and have received ≥1 cycle of IV rituximab maintenance within 16 weeks of completing induction. Pts (N = 154) were randomized 1:1 to receive SC rituximab (1400 mg) or IV rituximab (375 mg/m2) for their remaining maintenance cycles, stratified by 2-monthly (q2m) vs 3-monthly (q3m) regimen. Study arms were balanced for age, sex, body surface area, FL grade at diagnosis, induction therapy and number of maintenance doses prior to study entry. As of May 11, 2012, 13 SC pts had withdrawn (7 for progressive disease [PD], 4 for AEs, 1 at investigator's decision, 1 for ineligibility) and 17 IV pts had withdrawn (10 for PD, 4 for AEs, 3 for ineligibility). Median treatment duration on-study was 14.8 months (range, 0–19) in the SC arm and 13.8 months (range, 0–19) in the IV arm. The primary endpoint of the study was met. Geometric mean Ctrough,SC:Ctrough,IV ratios were 1.24 and 1.12, respectively, for q2m and q3m, and lower limits of the two-sided 90% CI (1.02 and 0.86, respectively) exceeded the protocol-specified non-inferiority limit (Ctrough,SC:Ctrough,IV ratio of 0.8). Therefore, 1400 mg SC rituximab was concluded to be non-inferior to 375 mg/m2 IV rituximab administration. AE incidence and intensity were generally balanced; 79% of pts in each arm experienced AEs. Serious AEs were observed in 12% and 14% of pts in the SC and IV arms, respectively; none occurred in > 1 pt in either arm. Grade 3/4 AEs occurred in 18% and 17% of pts in the SC and IV arms, respectively; the only grade 3/4 AEs occurring in > 1 pt in either arm were neutropenia (2 pts in each arm) and arthralgia (2 pts in the IV arm). Administration-related reactions (ARRs) were the most frequent AE and had a higher incidence in the SC arm (reported in 31% of SC vs 4% of IV pts). ARRs were mostly local reactions; the most common in the SC arm were: erythema (13%), injection site erythema (5%), and myalgia (5%). Further safety data will be presented. PK data for SC and IV rituximab administration demonstrate non-inferiority of 1400 mg rituximab SC administration to that of the approved IV rituximab maintenance regimen for both q2m and q3m schedules. The overall AE profiles were similar for SC and IV rituximab administration, with the exception of local ARRs, which had a higher incidence in the SC arm compared with the IV arm, reflecting the expected change in the ARR profile with SC administration. Induction and maintenance therapy using the 1400 mg SC rituximab dose is being assessed in the phase III BO22334 study.conferenceObject Final overall survival results of frontline bortezomib plus rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) vs R-CHOP in transplantation-ineligible patients (pts) with newly diagnosed mantle-cell lymphoma (MCL): A randomized, open-label, phase III (LYM-3002) study(2018) CAVALLI, F.; JIN, J.; PYLYPENKO, H.; VERHOEF, G.; SIRITANARATKUL, N.; DRACH, J.; RADERER, M.; MAYER, J.; PEREIRA, J.; TUMYAN, G.; OKAMOTO, R.; NAKAHARA, S.; HU, P.; APPIANI, C.; NEMAT, S.; ROBAK, T.conferenceObject Bortezomib (Btz) Dose Intensity Is the Strongest Predictor for Overall Survival (OS) in Mantle Cell Lymphoma (MCL) Patients (Pts) Not Considered for Transplantation, Receiving Frontline Btz Plus Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (VR-CAP) Therapy in the Phase 3 LYM-3002 Study(2014) ROBAK, Tadeusz; HUANG, Huiqiang; JIN, Jie; ZHU, Jun; LIU, Ting; SAMOILOVA, Olga S.; PYLYPENKO, Halyna; VERHOEF, Gregor; SIRITANARATKUL, Noppadol; OSMANOV, Evgenii A.; ALEXEEVA, Julia; PEREIRA, Juliana; MAYER, Jiri; HONG, Xiaonan; MAEDA, Yoshiharu; PEI, Lixia; ROONEY, Brendan; VELDE, Helgi van de; CAVALLI, Franco- Protocol for qRT-PCR analysis from formalin fixed paraffin embedded tissue sections from diffuse large b-cell lymphoma: Validation of the six-gene predictor score(2016) TEKIN, Nilgun; OMIDVAR, Nader; MORRIS, Tim Peter; CONGET, Paulette; BRUNA, Flavia; TIMAR, Botond; GAGYI, Eva; BASAK, Ranjan; NAIK, Omkar; AUEWARKUL, Chirayu; SRITANA, Narongrit; LEVY, Debora; CERCI, Juliano Julio; BYDLOWSKI, Sergio Paulo; PEREIRA, Juliana; DIMAMAY, Mark Pierre; NATIVIDAD, Filipinas; CHUNG, June-Key; BELDER, Nevin; KUZU, Isinsu; PAEZ, Diana; DONDI, Maurizio; CARR, Robert; OZDAG, Hilal; PADUA, Rose AnnAs a part of an international study on the molecular analysis of Diffuse Large B-cell Lymphoma (DLBCL), a robust protocol for gene expression analysis from RNA extraction to qRT-PCR using Formalin Fixed Paraffin Embedded tissues was developed. Here a study was conducted to define a strategy to validate the previously reported 6-gene (LMO2, BCL6, FN1, CCND2, SCYA3 and BCL2) model as predictor of prognosis in DLBCL. To avoid variation, all samples were tested in a single centre and single platform. This study comprised 8 countries (Brazil, Chile, Hungary, India, Philippines, S. Korea, Thailand and Turkey). Using the Kaplan-Meier and log rank test on patients (n=162) and two mortality risk groups (with those above and below the mean representing high and low risk groups) confirmed that the 6-gene predictor score correlates significantly with overall survival (OS, p< 0.01) but not with event free survival (EFS, p= 0.18). Adding the International Prognostic Index (IPI) shows that the 6-gene predictor score correlates significantly with high IPI scores for OS (p< 0.05), whereas those with low IPI scores show a trend not reaching significance (p= 0.08). This study defined an effective and economical qRT-PCR strategy and validated the 6-gene score as a predictor of OS in an international setting.
conferenceObject A Prospective, Multicenter, Randomized Study of Anti-CCR4 Monoclonal Antibody Mogamulizumab Versus Investigator's Choice in the Treatment of Patients with Relapsed/Refractory Adult T-Cell Leukemia-Lymphoma: Overall Response Rate, Progression-Free Survival, and Overall Survival(2016) PHILLIPS, Adrienne; FIELDS, Paul; HERMINE, Olivier; RAMOS, Juan Carlos; BELTRAN, Brady E.; PEREIRA, Juliana; BRITES, Carlos; WANDROO, Farooq Ahmad; LILL, Michael; FELDMAN, Tatyana A.; CASANOVA, Luis; JANAKIRAM, Murali; MENIANE, Jean-Come; SAWAS, Ahmed; COOK, Lucy B.; KURMAN, Michael R.; GEORGE, Joyce; DWYER, Karen; LEONI, Mollie; CONLON, Kevin; TAYLOR, Graham P.; GONSKY, Jason; HORWITZ, Steven M.- Comparison of Subcutaneous Versus Intravenous Administration of Rituximab As Maintenance Treatment for Follicular Lymphoma: Results From a Two-Stage, Phase IB Study(2014) SALAR, Antonio; AVIVI, Irit; BITTNER, Beate; BOUABDALLAH, Reda; BREWSTER, Mike; CATALANI, Olivier; FOLLOWS, George; HAYNES, Andrew; HOURCADE-POTELLERET, Florence; JANIKOVA, Andrea; LAROUCHE, Jean-Francois; MCINTYRE, Christine; PEDERSEN, Michael; PEREIRA, Juliana; SAYYED, Pakeeza; SHPILBERG, Ofer; TUMYAN, GayanePurpose This two-stage phase IB study investigated the pharmacokinetics and safety of subcutaneous (SC) versus intravenous (IV) administration of rituximab as maintenance therapy in follicular lymphoma. Patients and Methods In stage 1 (dose finding), 124 patients who responded to rituximab induction were randomly assigned to SC rituximab (375 mg/m(2), 625 mg/m(2), or an additional group at 800 mg/m(2)) or IV rituximab (375 mg/m(2)). The objective was to determine an SC dose that would yield a rituximab serum trough concentration (C-trough) in the same range as that of IV rituximab. In stage 2, 154 additional patients were randomly assigned (1: 1) to SC rituximab (1,400 mg) or IV rituximab (375 mg/m(2)) given at 2-or 3-month intervals. The objective was to demonstrate noninferior rituximab C-trough of SC rituximab relative to IV rituximab 375 mg/m(2). Results Stage 1 data predicted that a fixed dose of 1,400 mg SC rituximab would result in a serum C-trough in the range of that of IV rituximab. Noninferiority (ie, meeting the prespecified 90% CI lower limit of 0.8) was then confirmed in stage 2, with geometric mean C-trough (SC): C-trough (IV) ratios for the 2-and 3-month regimens of 1.24 (90% CI, 1.02 to 1.51) and 1.12 (90% CI, 0.86 to 1.45), respectively. Overall safety profiles were similar between formulations (in stage 2, 79% of patients experienced one or more adverse events in each group). Local administration-related reactions (mainly mild to moderate) occurred more frequently after SC administration. Conclusion The fixed dose of 1,400 mg SC rituximab predicted by using stage 1 results was confirmed to have noninferior C-trough levels relative to IV rituximab 375 mg/m(2) dosing during maintenance, with a comparable safety profile. Additional investigation will be required to determine whether the SC route of administration for rituximab provides equivalent efficacy compared with that of IV administration. (C) 2014 by American Society of Clinical Oncology