Search results for "Refractory"
showing 10 items of 253 documents
An open-label phase II study of ibrutinib in patients with refractory follicular lymphoma
2013
TPS8614^ Background: Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL) and comprises approximately 22% of all NHL cases. Most patients treated eventually relapse and subsequent responses and duration of responses become shorter. Patients ultimately become resistant to chemoimmunotherapy and repeated treatment-related toxicity commonly outweighs the benefit of treatment. Ibrutinib is a potent inhibitor of BTK (downstream of the B-cell receptor, BCR) that binds covalently to Cys-481 in the active site, abrogating intrinsic survival pathways (eg, ERK1/2, NF-kB, AKT) as well as survival signals from the microenvironment (eg, TNF family members: BAFF, CD40L; cytokine…
The mTOR Inhibitor Temsirolimus Added to Rituximab Combined With Dexamethasone, Cytarabine, and Cisplatinum (R-DHAP) for the Treatment of Patients Wi…
2021
There is a high need for novel treatment options in relapsed and refractory diffuse large B-cell lymphoma. Single agent mammalian target of rapamycin (mTOR) inhibitor treatment has shown promising efficacy in this entity. Here, we report on the results of the mTOR-inhibitor temsirolimus combined to standard rituximab-DHAP salvage regimen in a prospective, multicenter, phase II, open-label study. The STORM regimen consisted of rituximab 375 mg/m(2) (day 2) and DHAP (dexamethasone 40 mg day 3-6, cisplatinum 100 mg/m(2) day 3, cytarabine 2 × 2 g/m(2) day 4) with temsirolimus added on day 1 and 8 of a 21-day cycle, with 2 to 4 cycles planned. In part I, dose levels of 25, 50, 75, and 100 mg fo…
Durability of complete response after blinatumomab therapy for refractory/relapsed aggressive B-cell non-Hodgkin lymphoma.
2019
e19041 Background: Achieving durable response in patients (pts) with relapsed/refractory (R/R) aggressive B-cell lymphoma (B-NHL) is challenging. Blinatumomab, a bispecific T-cell engager (BiTE) immunotherapy targeting CD19-expressing cancer cells, has shown promising efficacy in pts with R/R aggressive B-NHL. We report the durability of complete response (DOCR) in pts treated with blinatumomab. Methods: The DOCR in pts with R/R aggressive B-NHL responding to blinatumomab was assessed using data from two phase 2 studies (study 1 [N = 25], NCT01741792; study 2 [N = 41], NCT02910063) in pts with R/R aggressive B-NHL. CR was assessed using Cheson (study 1) and Lugano (study 2) criteria. Time-…
Updated results from BELLINI, a phase III study of venetoclax or placebo in combination with bortezomib and dexamethasone in relapsed/refractory mult…
2020
8509 Background: Venetoclax (Ven) is a selective, potent, oral BCL-2 inhibitor. In the Phase 3 BELLINI trial, addition of Ven to bortezomib (B) + dexamethasone (d) significantly improved response rates and progression-free survival (PFS) vs placebo (Pbo) and showed significant efficacy in patients (pts) with either t(11;14) or BCL2high gene expression. Here we present updated safety and efficacy data from the prespecified second interim overall survival (OS) analysis. Methods: In this multicenter, randomized, double-blind study (NCT02755597), pts with relapsed/refractory multiple myeloma (RRMM) with 1-3 prior lines of therapy were randomized 2:1 to Ven (800 mg) or Pbo in combination with B…
Ofatumumab retreatment and maintenance in patients with fludarabine-refractory CLL.
2012
6584 Background: In Study 406, the anti-CD20 monoclonal antibody ofatumumab (ofa), given as monotherapy over 6 months, showed 47% overall response rate (ORR) in patients (pts) with chronic lymphocytic leukemia (CLL) refractory to fludarabine and alemtuzumab (FA-ref), or to fludarabine with bulky (>5cm) lymphadenopathy (BF-ref). The effects of ofa retreatment (retx) and maintenance (mt) are unknown. Methods: Pts who responded to ofa and then progressed or had stable disease (SD) in Study 406, were offered retx in Study 416 (NCT00802737; GSK/Genmab) with ofa 1 x 300 mg + 7 x 2000 mg weekly followed by mt with ofa 2000 mg monthly for up to 2 years (if SD or better). Primary endpoint was OR…
Associations of ofatumumab exposure and treatment outcomes in patients with untreated CLL receiving chemoimmunotherapy
2016
Relationships between patient characteristics, ofatumumab pharmacokinetics, and treatment outcomes were investigated in this phase 2 trial of ofatumumab plus fludarabine and cyclophosphamide (FC) in untreated chronic lymphocytic leukemia. Patients were randomized 1:1 to receive 500 or 1000 mg ofatumumab (Cycle 1; 300 mg) plus FC every 4 weeks for six cycles. Median C(max) and C(trough) values were similar at Cycle 1 regardless of the ultimate clinical outcome. At later doses, these values were higher for patients with complete response (CR) than for other patients. Higher C(max) and C(trough) values at Cycles 3 and 6 were significantly associated with an increased likelihood of CR, whereas …
FCGR polymorphisms and cetuximab efficacy in chemorefractory metastatic colorectal cancer: an international consortium study
2015
OBJECTIVE: We aimed to better clarify the role of germline variants of the FCG2 receptor, FCGR2A-H131R and FCGR3A-V158F, on the therapeutic efficacy of cetuximab in metastatic colorectal cancer (mCRC). A large cohort with sufficient statistical power was assembled.DESIGN: To show a HR advantage of 0.6 in progression-free survival (PFS) for FCGR2A-HH versus the rest and FCGR3A-VV versus the rest, with an 80% power, 80 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) wild-type (KRAS-WT) and 52 KRAS-WT patients are required, respectively. This leads to a total sample size of 952 and 619 patients, respectively. Samples were collected from 1123 mCRC patients from 15 European centres treated wit…
Oral chemotherapy in hormone-refractory prostate carcinoma patients unwilling to be admitted to hospital.
2008
<i>Objectives:</i> To investigate the safety and efficacy in terms of PSA response of a low-dose oral combination of estramustine phosphate (EMP) and etoposide (VP16) in hormone- refractory prostate cancer (HRPC) patients. Well-tolerated outpatient chemotherapy regimens for patients unfit and/or unwilling to be admitted to hospital are needed. <i>Methods:</i> Fifty-six HRPC patients with metastatic disease (median age 75 years) were randomized between arm A (daily oral EMP 10 mg/kg, in 3 doses) and arm B (28-day cycle with low-dose EMP 3 mg/kg once daily plus VP16 25 mg/m<sup>2</sup> once daily on days 1 through 14). Baseline characteristics between the t…
PSA and second-line therapy of hormone refractory prostate carcinoma
2001
The aim of the present study was to correlate PSA response with subjective response (bone pain and performance status), in patients treated for hormone refractory carcinoma of the prostate. Twenty-four patients were introduced into the study. Median PSA was 198 ng/ml. Symptom score, performance status and PSA were monitored monthly for 3 months and then 3-monthly. Sixteen patients (66%) showed a PSA response (median value 10 ng/ml). In 8 patients (33%) PSA was 4 ng/ml. In conclusion, PSA response is not always related to subjective improvement and does not always implicate a beneficial effect of the therapy for the patient. Copyright © 2001 S. Karger AG, Basel.
Safety of ninety-minute daratumumab infusion.
2020
Purpose Daratumumab is the first anti-CD38 monoclonal antibody of the class approved for recurrent and refractory multiple myeloma. Grade 3 and 4 Infusion-Related Reactions (IRRs) are frequent during the first and second infusions. Due to the risks associated with severe IRRs, daratumumab is systematically administered over a period of 3.5 hours. The main objective of this study was to evaluate the safety of a 90-minute daratumumab infusion from the third infusion. Patients and methods All patients who had received two or more doses of daratumumab in monotherapy or in combination with standard infusion rates were included. We excluded patients enrolled in clinical trials. For the rapid infu…