A5054841750- Chronic Lymphocytic Leukemia Research
- Lymphoma Diagnosis and Treatment
- Chronic Myeloid Leukemia Treatments
- Acute Lymphoblastic Leukemia research
- Gastrointestinal Tumor Research and Treatment
- Immunodeficiency and Autoimmune Disorders
- Phagocytosis and Immune Regulation
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer Mechanisms and Therapy
- Monoclonal and Polyclonal Antibodies Research
- Acute Myeloid Leukemia Research
- Renal Diseases and Glomerulopathies
- Cancer therapeutics and mechanisms
- Platelet Disorders and Treatments
- Peptidase Inhibition and Analysis
- Methemoglobinemia and Tumor Lysis Syndrome
- Advanced Breast Cancer Therapies
Pharmacyclics (United States)
2015-2023
AbbVie (United States)
2015-2023
Geron (United States)
2011
CAPTIVATE (NCT02910583), a randomized phase II study, evaluates minimal residual disease (MRD)-guided treatment discontinuation following completion of first-line ibrutinib plus venetoclax in patients with chronic lymphocytic leukemia (CLL).Previously untreated CLL age < 70 years received three cycles and then 12 combined venetoclax. Patients the MRD cohort who met stringent random assignment criteria for confirmed undetectable (Confirmed uMRD) were randomly assigned 1:1 to double-blind...
CAPTIVATE (NCT02910583) is an international phase 2 study in patients aged ≤70 years with previously untreated chronic lymphocytic leukemia (CLL). Results from the cohort investigating fixed-duration (FD) treatment ibrutinib plus venetoclax are reported. Patients received 3 cycles of lead-in then 12 (oral [420 mg/d]; oral [5-week ramp-up to 400 mg/d]). The primary endpoint was complete response (CR) rate. Hypothesis testing performed for without del(17p) prespecified analyses all treated...
Summary Bleeding events have been observed among a subgroup of chronic lymphocytic leukaemia ( CLL ) patients treated with ibrutinib. We analysed data from two studies single‐agent ibrutinib to better characterize bleeding and pattern anticoagulation antiplatelet use. Among 327 ibrutinib‐treated patients, concomitant (11%) or use (34%) was common, but major infrequent (2%). were primarily grade 1, infrequently (1%) led discontinuation. 175 receiving anticoagulant agents, 5 had (3%). These...
BackgroundCertain genomic features, such as del(11q), expression of unmutated immunoglobulin heavy-chain variable region (IGHV) gene, or complex karyotype, predict poorer outcomes to chemotherapy in patients with chronic lymphocytic leukemia (CLL).Patients and MethodsWe examined the pooled long-term follow-up data from PCYC-1115 (RESONATE-2), PCYC-1112 (RESONATE), CLL3001 (HELIOS), comprising a total 1238 subjects, determine prognostic significance these markers treated ibrutinib.ResultsWith...
Abstract The efficacy of ibrutinib has been demonstrated in patients with chronic lymphocytic leukemia (CLL), including as first‐line therapy. However, outcomes after discontinuation have previously limited to higher‐risk populations relapsed/refractory (R/R) disease. objective this study was evaluate ibrutinib‐treated based on prior lines therapy, discontinuation. Data were analyzed from two multicenter phase 3 studies single‐agent ibrutinib: RESONATE (PCYC‐1112) R/R CLL and RESONATE‐2...
7501 Background: CAPTIVATE (PCYC-1142) is a multicenter phase 2 study of first-line I+V in CLL. We previously reported results from the Minimal Residual Disease (MRD) cohort wherein undetectable MRD (uMRD) was achieved over two-thirds patients (pts) with 12 cycles I+V, and 30-mo PFS rates were ≥95% irrespective subsequent randomized treatment (Wierda, ASH 2020). now present FD cohort, evaluating fixed-duration tx I+V. Methods: Pts aged ≤70 y untreated CLL/SLL received 3 I then (I 420 mg/d...
7502 Background: Ibr, a first-in-class, once-daily BTK inhibitor, is approved in the US and EU for CLL treatment, including del17p. Early studies support synergistic antitumor activity with combined ibr ven, BCL-2 inhibitor by FDA relapsed del17p CLL. Single-agent lead-in may lower tumor lysis syndrome (TLS) risk debulking prior to adding ven. PCYC-1142 (CAPTIVATE) multicenter, phase 2 study of + ven (I+V) first-line (NCT02910583) evaluating if remission undetectable minimal residual disease...
Increased absolute lymphocyte count (ALC) is a key feature of chronic lymphocytic leukemia (CLL) but also observed during treatment with B-cell receptor pathway inhibitors including ibrutinib, first-in-class inhibitor Bruton's tyrosine kinase. In patients CLL treated single-agent ibrutinib in two multicenter, open-label, randomized, phase 3 studies (RESONATE-2, NCT01722487; RESONATE, NCT01578707), lymphocytosis was 77 136 (57%) first-line and 133 195 (69%) relapsed/refractory patients. On...
Abstract Purpose: The phase II CAPTIVATE study investigated first-line treatment with ibrutinib plus venetoclax for chronic lymphocytic leukemia in two cohorts: minimal residual disease (MRD)-guided randomized discontinuation (MRD cohort) and fixed duration (FD cohort). We report tumor debulking lysis syndrome (TLS) risk category reduction three cycles of single-agent lead-in before initiation using pooled data from the MRD FD cohorts. Patients Methods: In both cohorts, patients initially...
7520 Background: Ibrutinib (ibr) is the first-in-class once daily Bruton’s tyrosine kinase inhibitor FDA approved for patients (pts) with CLL ≥ 1 prior therapy. We evaluated outcomes ibr based on lines of therapy (LoT), and following discontinuation (DC) in pts CLL. Methods: analyzed data from two phase 3 trials ibr: PCYC-1115/16 (RESONATE-2) 65 treatment naïve (TN) CLL; PCYC-1112 (RESONATE) previously treated (PT) CLL, excluding del17p a more homogenous dataset analysis. Progression-free...
Few therapies are approved for hospitalized patients with severe coronavirus disease 2019 (COVID-19). Ibrutinib, a once-daily Bruton tyrosine kinase inhibitor, may mitigate COVID-19-induced lung damage by reducing inflammatory cytokines. The multicenter, randomized, double-blind phase 2 iNSPIRE study evaluated ibrutinib prevention of respiratory failure in COVID-19. Adult COVID-19 requiring hospitalization and supplemental oxygen but without were randomized 1:1 (stratified remdesivir...
Introduction: In phase 3 studies, ibrutinib (ibr) was superior to ofatumumab in relapsed/refractory (R/R) CLL/SLL or chlorambucil treatment (tx)-naïve (TN) CLL/SLL. Ibr + bendamustine/rituximab (BR) BR R/R Clinical outcomes of pts these studies were examined determine the impact certain prognostic risk factors other than del17p. Methods: RESONATE: CLL/SLL, ibr 420 mg/d until progressive disease (PD) (≤24 wk). RESONATE-2: TN (no del17p) ≥65 y, PD (≤12 cycles). HELIOS: del17p), (≤6 cycles) ±...
Background: Ibrutinib, a first-in-class, once-daily inhibitor of Bruton's tyrosine kinase (BTK), is approved in the US and EU for treatment various B-cell malignancies. In clinical studies, BTK inhibitors have been associated with increased bleeding risk, which may result from inhibition platelets.Methods: To better understand mechanism ibrutinib events, we isolated platelet-rich plasma healthy donors (n = 8) conditions impaired platelet function or potentially risk (on hemodialysis, taking...
Abstract Background: Patients (pts) with CLL/SLL who use unmutated IGHV (u-CLL) have a less favorable outcome standard chemotherapy than pts mutated (m-CLL). Ibrutinib (ibr) inhibits B-cell receptor signaling through Bruton’s tyrosine kinase and has robust clinical activity against CLL. This integrated analysis of 3 phase studies examined the impact status on ibr- comparator (comp)-treated pts. Methods: Pooled data from ibr (420 mg/d) in (RESONATE: relapsed/refractory [R/R] pts, vs ≤ 24...
Introduction: Over two-thirds of patients (pts) in the Minimal Residual Disease (MRD) cohort CAPTIVATE (PCYC-1142; NCT02910583), a multicenter phase 2 study, achieved undetectable MRD (uMRD) with 12 cycles ibrutinib (I) + venetoclax (V). ≥95% pts were progression free at 30 mo irrespective subsequent randomized treatment (Wierda, ASH 2020). Here we present results from Fixed Duration (FD) cohort. Methods: Eligible aged ≤70 y and had not received previous for CLL/SLL. Pts 3 I then I+V (I 420...
Introduction: Younger, fit patients (pts) with CLL generally receive first-line treatment chemoimmunotherapy (CIT) regimens such as fludarabine, cyclophosphamide and rituximab (FCR), which can eliminate minimal residual disease (MRD) (Bottcher, JCO 2012; Strati, Blood 2014). MRD has emerged an important endpoint that correlates survival. MRD-negative remission FCR is less frequent, however, in pts unmutated IGHV genes del(17p) (Thompson, 2016). Ibrutinib (ibr), a first-in-class, once-daily...