Search

Your search keyword '"Busman, Todd"' showing total 24 results
Start Over Author "Busman, Todd" Search Limiters Full Text
24 results on '"Busman, Todd"'

1. Activity of venetoclax in patients with relapsed or refractory chronic lymphocytic leukaemia: analysis of the VENICE-1 multicentre, open-label, single-arm, phase 3b trial

Author

Genetica Sectie Genoomdiagnostiek, Kater, Arnon P., Arslan, Önder, Demirkan, Fatih, Herishanu, Yair, Ferhanoglu, Burhan, Diaz, Marcos Gonzalez, Leber, Brian, Montillo, Marco, Panayiotidis, Panayiotis, Rossi, Davide, Skarbnik, Alan, Tempescul, Adrian, Turgut, Mehmet, Mellink, Clemens H., van der Kevie-Kersemaekers, Anne Marie F., Lanham, Stuart, Sale, Ben, Del Rio, Luis, Popovic, Relja, Chyla, Brenda J., Busman, Todd, Komlosi, Viktor, Wang, Xifeng, Sail, Kavita, Pena, German E., Vizkelety, Tamas, Forconi, Francesco, Genetica Sectie Genoomdiagnostiek, Kater, Arnon P., Arslan, Önder, Demirkan, Fatih, Herishanu, Yair, Ferhanoglu, Burhan, Diaz, Marcos Gonzalez, Leber, Brian, Montillo, Marco, Panayiotidis, Panayiotis, Rossi, Davide, Skarbnik, Alan, Tempescul, Adrian, Turgut, Mehmet, Mellink, Clemens H., van der Kevie-Kersemaekers, Anne Marie F., Lanham, Stuart, Sale, Ben, Del Rio, Luis, Popovic, Relja, Chyla, Brenda J., Busman, Todd, Komlosi, Viktor, Wang, Xifeng, Sail, Kavita, Pena, German E., Vizkelety, Tamas, and Forconi, Francesco

Published
2024

2. A Phase I study of the safety, pharmacokinetics and efficacy of navitoclax plus docetaxel in patients with advanced solid tumors

Author

Puglisi, Martina, primary, Molife, L Rhoda, additional, de Jonge, Maja JA, additional, Khan, Khurum H, additional, Doorn, Leni van, additional, Forster, Martin D, additional, Blanco, Montserrat, additional, Gutierrez, Martin, additional, Franklin, Catherine, additional, Busman, Todd, additional, Yang, Jianning, additional, and Eskens, Ferry ALM, additional

Published
2021
Full Text
View/download PDF

3. Comprehensive Safety Analysis of Venetoclax Monotherapy for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia

Author

Davids, Matthew S., Hallek, Michael, Wierda, William, Roberts, Andrew W., Stilgenbauer, Stephan, Jones, Jeffrey A., Gerecitano, John F., Kim, Su Young, Potluri, Jalaja, Busman, Todd, Best, Andrea, Verdugo, Maria E., Cerri, Elisa, Desai, Monali, Hillmen, Peter, Seymour, John F., Davids, Matthew S., Hallek, Michael, Wierda, William, Roberts, Andrew W., Stilgenbauer, Stephan, Jones, Jeffrey A., Gerecitano, John F., Kim, Su Young, Potluri, Jalaja, Busman, Todd, Best, Andrea, Verdugo, Maria E., Cerri, Elisa, Desai, Monali, Hillmen, Peter, and Seymour, John F.

Abstract

Purpose: The oral BCL-2 inhibitor venetoclax is an effective therapy for patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), including disease with high-risk genomic features such as chromosome 17p deletion [del (17p)] or progressive disease following B-cell receptor pathway inhibitors. Patients and Methods: We conducted a comprehensive analysis of the safety of 400 mg daily venetoclax monotherapy in 350 patients with CLL using an integrated dataset from three phase I/II studies. Results: Median age was 66 years and 60% had del(17p). Patients had received a median of three prior therapies (range: 0-15); 42% previously received ibrutinib or idelalisib. Median duration of exposure to venetoclax was 16 months (0-56). In the pooled analysis, the most common adverse events (AE) of any grade were diarrhea (41%), neutropenia (40%), nausea (39%), anemia (31%), fatigue (28%), and upper respiratory tract infection (25%). The most common grade 3/4 AEs were neutropenia (37%), anemia (17%), and thrombocytopenia (14%). With the current 5-week ramp-up dosing, the incidence of laboratory TLS was 1.4% (2/166), none had clinical sequelae, and all of these patients were able to ramp-up to a daily dose of 400 mg. Grade 3/4 neutropenia was manageable with growth factor support and dose adjustments; the incidence of serious infections in these patients was 15%. Ten percent of patients discontinued venetoclax due to AEs and 8% died while on study, with the majority of deaths in the setting of disease progression. Conclusions: Venetoclax as a long-term continuous therapy is generally well tolerated in patients with R/R CLL when initiated with the current treatment algorithm. (C) 2018 AACR.

Published
2018

4. Comprehensive Safety Analysis of Venetoclax Monotherapy for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia

Author

Davids, Matthew S., primary, Hallek, Michael, additional, Wierda, William, additional, Roberts, Andrew W., additional, Stilgenbauer, Stephan, additional, Jones, Jeffrey A., additional, Gerecitano, John F., additional, Kim, Su Young, additional, Potluri, Jalaja, additional, Busman, Todd, additional, Best, Andrea, additional, Verdugo, Maria E., additional, Cerri, Elisa, additional, Desai, Monali, additional, Hillmen, Peter, additional, and Seymour, John F., additional

Published
2018
Full Text
View/download PDF

5. Safety Profile of Venetoclax Monotherapy in Patients with Chronic Lymphocytic Leukemia

Author

Seymour, John F, primary, Davids, Matthew S., additional, Roberts, Andrew W., additional, Hallek, Michael, additional, Wierda, William G., additional, Hillmen, Peter, additional, Gerecitano, John F., additional, Cerri, Elisa, additional, Potluri, Jalaja, additional, Kim, Su Young, additional, Busman, Todd, additional, Verdugo, Maria, additional, Humerickhouse, Rod A., additional, Best, Andrea, additional, Desai, Monali, additional, and Stilgenbauer, Stephan, additional

Published
2016
Full Text
View/download PDF

6. Safety Profile of Venetoclax Monotherapy in Patients with Chronic Lymphocytic Leukemia

Author

Seymour, John F., Davids, Matthew S., Roberts, Andrew W., Hallek, Michael, Wierda, William G., Hillmen, Peter, Gerecitano, John F., Cerri, Elisa, Potluri, Jalaja, Kim, Su Young, Busman, Todd, Verdugo, Maria, Humerickhouse, Rod A., Best, Andrea, Desai, Monali, Stilgenbauer, Stephan, Seymour, John F., Davids, Matthew S., Roberts, Andrew W., Hallek, Michael, Wierda, William G., Hillmen, Peter, Gerecitano, John F., Cerri, Elisa, Potluri, Jalaja, Kim, Su Young, Busman, Todd, Verdugo, Maria, Humerickhouse, Rod A., Best, Andrea, Desai, Monali, and Stilgenbauer, Stephan

Published
2016

7. Preliminary Results of a Phase 2, Open-Label Study of Venetoclax (ABT-199/GDC-0199) Monotherapy in Patients with Chronic Lymphocytic Leukemia Relapsed after or Refractory to Ibrutinib or Idelalisib Therapy

Author

Jones, Jeffrey, primary, Mato, Anthony R., additional, Coutre, Steven, additional, Wierda, William, additional, Choi, Michael Y., additional, Davids, Matthew S., additional, Lamanna, Nicole, additional, Barr, Paul, additional, Burns, Kim, additional, Montalvo, Nicholas, additional, Zhu, Ming, additional, Busman, Todd, additional, Potluri, Jalaja, additional, Humerickhouse, Rod A., additional, and Byrd, John C., additional

Published
2015
Full Text
View/download PDF

8. Safety, Pharmacokinetics, Pharmacodynamics, and Activity of Navitoclax, a Targeted High Affinity Inhibitor of BCL-2, in Lymphoid Malignancies

Author

Wilson, Wyndham H., O’Connor, Owen A., Czuczman, Myron S., LaCasce, Ann S., Gerecitano, John F., Leonard, John P., Tulpule, Anil, Dunleavy, Kieron, Xiong, Hao, Chiu, Yi-Lin, Cui, Yue, Busman, Todd, Elmore, Steven W., Rosenberg, Saul H., Krivoshik, Andrew P., Enschede, Sari H., and Humerickhouse, Rod A.

Subjects
Blood Platelets, Dosage Forms, Sulfonamides, Aniline Compounds, Lymphoma, Maximum Tolerated Dose, T-Lymphocytes, Antineoplastic Agents, Middle Aged, Survival Analysis, Article, Drug Delivery Systems, Proto-Oncogene Proteins c-bcl-2, Humans, Aged
Abstract

Proteins of the BCL-2 family regulate clonal selection and survival of lymphocytes, and are frequently overexpressed in lymphomas. Navitoclax is a targeted high-affinity small molecule that inhibits the anti-apoptotic activity of BCL-2 and BCL-XL. We aimed to assess the safety and antitumour activity of navitoclax in patients with lymphoid tumours, and establish the drug's pharmacokinetic and pharmacodynamic profiles.In this phase 1 dose-escalation study, patients (aged ≥18 years) with relapsed or refractory lymphoid malignancies were enrolled and treated at seven sites in the USA between November, 2006, and November, 2009. A modified Fibonacci 3+3 design was used to assign patients to receive oral navitoclax once daily by one of two dosing schedules: intermittently for the first 14 days of a 21-day cycle (14/21) at doses of 10, 20, 40, 80, 110, 160, 225, 315, or 440 mg/day; or continuously for 21 days of a 21-day cycle (21/21) at doses of 200, 275, 325, or 425 mg/day. Study endpoints were safety, maximum tolerated dose, pharmacokinetic profile, pharmacodynamic effects on platelets and T cells, and antitumour activity. This trial is registered with ClinicalTrials.gov, number NCT00406809.55 patients were enrolled (median age 59 years, IQR 51-67), 38 to receive the 14/21 dosing schedule, and 17 to receive the 21/21 dosing schedule. Common toxic effects included grade 1 or 2 anaemia (41 patients), infection (39), diarrhoea (31), nausea (29), and fatigue (21); and grade 3 or 4 thrombocytopenia (29), lymphocytopenia (18), and neutropenia (18). On the intermittent 14/21 schedule, dose-limiting toxic effects were hospital admissions for bronchitis (one) and pleural effusion (one), grade 3 increase in aminotransferases (one), grade 4 thrombocytopenia (one), and grade 3 cardiac arrhythmia (one). To reduce platelet nadir associated with intermittent 14/21 dosing, we assessed a 150 mg/day lead-in dose followed by a continuous 21/21 dosing schedule. On the 21/21 dosing schedule, two patients did not complete the first cycle and were excluded from assessment of dose-limiting toxic effects; dose-limiting toxic effects were grade 4 thrombocytopenia (one), grade 3 increase in aminotransferases (one), and grade 3 gastrointestinal bleeding (one). Navitoclax showed a pharmacodynamic effect on circulating platelets and T cells. Clinical responses occurred across the range of doses and in several tumour types. Ten of 46 patients with assessable disease had a partial response, and these responders had median progression-free survival of 455 days (IQR 40-218).Navitoclax has a novel mechanism of peripheral thrombocytopenia and T-cell lymphopenia, attributable to high-affinity inhibition of BCL-XL and BCL-2, respectively. On the basis of these findings, a 150 mg 7-day lead-in dose followed by a 325 mg dose administered on a continuous 21/21 dosing schedule was selected for phase 2 study.Abbott Laboratories, Genentech, and National Cancer Institute, National Institutes of Health.

Published
2010

9. A Phase 2 Study of ABT-199 (GDC-0199) in Patients with Acute Myelogenous Leukemia (AML)

Author

Konopleva, Marina, primary, Pollyea, Daniel A., additional, Potluri, Jalaja, additional, Chyla, Brenda J., additional, Busman, Todd, additional, McKeegan, Evelyn, additional, Salem, Ahmed, additional, Zhu, Ming, additional, Ricker, Justin L., additional, Blum, William, additional, DiNardo, Courtney D., additional, Dunbar, Martin, additional, Kirby, Rachel, additional, Falotico, Nancy, additional, Leverson, Joel D., additional, Humerickhouse, Rod A., additional, Mabry, Mack, additional, Stone, Richard M., additional, Kantarjian, Hagop M., additional, and Letai, Anthony G., additional

Published
2014
Full Text
View/download PDF

10. The Single-Agent Bcl-2 Inhibitor ABT-199 (GDC-0199) In Patients With Relapsed/Refractory (R/R) Non-Hodgkin Lymphoma (NHL): Responses Observed In All Mantle Cell Lymphoma (MCL) Patients

Author

Davids, Matthew S., primary, Seymour, John F., additional, Gerecitano, John F., additional, Kahl, Brad S., additional, Pagel, John M., additional, Wierda, William G., additional, Anderson, Mary-Ann, additional, Rudersdorf, Nikita K., additional, Gressick, Lori A., additional, Montalvo, Nicholas P., additional, Yang, Jianning, additional, Busman, Todd A., additional, Dunbar, Martin, additional, Cerri, Elisa, additional, Enschede, Sari H., additional, Humerickhouse, Rod A., additional, and Roberts, Andrew W., additional

Published
2013
Full Text
View/download PDF

11. The BCL-2-Specific BH3-Mimetic ABT-199 (GDC-0199) Is Active and Well-Tolerated in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia: Interim Results of a Phase I First-in-Human Study

Author

Seymour, John F., primary, Davids, Matthew S., additional, Anderson, Mary Ann, additional, Kipps, Thomas J., additional, Wierda, William G., additional, Pagel, John M., additional, Kahl, Brad S., additional, Miller, Thomas P., additional, Darden, David E., additional, Nolan, Cathy E., additional, Gressick, Lori A., additional, Xiong, Hao, additional, Huang, David C.S., additional, Chyla, Brenda J., additional, Busman, Todd A., additional, Graham, Alison M., additional, Cerri, Elisa, additional, Enschede, Sari H., additional, Humerickhouse, Rod A., additional, and Roberts, Andrew W., additional

Published
2012
Full Text
View/download PDF

12. The BCL-2-Specific BH3-Mimetic ABT-199 (GDC-0199) Is Active and Well-Tolerated in Patients with Relapsed Non-Hodgkin Lymphoma: Interim Results of a Phase I Study

Author

Davids, Matthew S., primary, Roberts, Andrew W., additional, Anderson, Mary Ann, additional, Pagel, John M., additional, Kahl, Brad S., additional, Gerecitano, John F., additional, Darden, David E., additional, Nolan, Cathy E., additional, Gressick, Lori A., additional, Yang, Jianning, additional, Chyla, Brenda J., additional, Busman, Todd A., additional, Graham, Alison M., additional, Cerri, Elisa, additional, Enschede, Sari H., additional, Humerickhouse, Rod A., additional, and Seymour, John F., additional

Published
2012
Full Text
View/download PDF

13. Phase II Study of Single-Agent Navitoclax (ABT-263) and Biomarker Correlates in Patients with Relapsed Small Cell Lung Cancer

Author

Rudin, Charles M., primary, Hann, Christine L., additional, Garon, Edward B., additional, Ribeiro de Oliveira, Moacyr, additional, Bonomi, Philip D., additional, Camidge, D. Ross, additional, Chu, Quincy, additional, Giaccone, Giuseppe, additional, Khaira, Divis, additional, Ramalingam, Suresh S., additional, Ranson, Malcolm R., additional, Dive, Caroline, additional, McKeegan, Evelyn M., additional, Chyla, Brenda J., additional, Dowell, Barry L., additional, Chakravartty, Arunava, additional, Nolan, Cathy E., additional, Rudersdorf, Niki, additional, Busman, Todd A., additional, Mabry, Mack H., additional, Krivoshik, Andrew P., additional, Humerickhouse, Rod A., additional, Shapiro, Geoffrey I., additional, and Gandhi, Leena, additional

Published
2012
Full Text
View/download PDF

14. Navitoclax (ABT-263) Plus Fludarabine/Cyclophosphamide/Rituximab (FCR) or Bendamustine/Rituximab (BR): A Phase 1 Study in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL),

Author

Kipps, Thomas J., primary, Swinnen, Lode J., additional, Wierda, William G., additional, Jones, Jeffrey Alan, additional, Coutre, Steven E., additional, Smith, Mitchell R, additional, Yang, Jianning, additional, Cui, Yue, additional, Busman, Todd, additional, Enschede, Sari, additional, and Humerickhouse, Rod, additional

Published
2011
Full Text
View/download PDF

15. Abstract A92: A phase 1 safety and pharmacokinetic study of navitoclax in combination with docetaxel in patients with solid tumors.

Author

Eskens, Ferry ALM, primary, Gutierrez, Martin, additional, Cosgrove, David, additional, Puglisi, Martina, additional, van Doorn, Leni, additional, Blanco, Montserrat, additional, de Jonge, Maja JA, additional, Moran, Kirsty, additional, Walther, Axel, additional, Yang, Jianning, additional, Busman, Todd A., additional, Franklin, Catherine A., additional, Mabry, Mack H., additional, Humerickhouse, Rod A., additional, and Molife, Lulama Rhoda, additional

Published
2011
Full Text
View/download PDF

16. Abstract A93: Safety, efficacy and pharmacokinetics of two schedules of navitoclax (ABT-263) in combination with irinotecan: Preliminary results of an open-label phase 1 study.

Author

Tolcher, Anthony W., primary, LoRusso, Patricia, additional, Rosen, Lee, additional, de Oliveira, Moacyr Ribeiro, additional, Waring, Jeffrey F., additional, Rudersdorf, Niki, additional, Patel, Raina, additional, Brasher, Carol Ann, additional, Busman, Todd, additional, Cui, Yue, additional, Yang, Jianning, additional, and Holen, Kyle, additional

Published
2011
Full Text
View/download PDF

18. Navitoclax (ABT-263) Plus Fludarabine/Cyclophosphamide/Rituximab (FCR) or Bendamustine/Rituximab (BR): A Phase 1 Study In Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)

Author

Kipps, Thomas J., primary, Wierda, William G., additional, Jones, Jeffrey A., additional, Swinnen, Lode J., additional, Yang, Jianning, additional, Cui, Yue, additional, Busman, Todd, additional, Krivoshik, Andrew, additional, Enschede, Sari, additional, and Humerickhouse, Rod, additional

Published
2010
Full Text
View/download PDF

19. An Ongoing Phase 1/2a Study of ABT-263; Pharmacokinetics (PK), Safety and Anti-Tumor Activity in Patients (pts) with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL).

Author

Roberts, Andrew W., primary, Seymour, John F, additional, Brown, Jennifer R, additional, Wierda, William G, additional, Kipps, Thomas J., additional, Carney, Dennis, additional, Xiong, Hao, additional, Cui, Yue, additional, Busman, Todd, additional, Enschede, Sari, additional, Krivoshik, Andrew, additional, and Humerickhouse, Rod, additional

Published
2009
Full Text
View/download PDF

20. Phase 1/2a Study of ABT-263 in Relapsed or Refractory Lymphoid Malignancies.

Author

Wilson, Wyndham H, primary, O'Connor, Owen A, additional, Czuczman, Myron S, additional, LaCasce, Ann, additional, Gerecitano, John, additional, Leonard, John P., additional, Tulpule, Anil, additional, Xiong, Hao, additional, Chiu, Yi-Lin, additional, Busman, Todd, additional, Enschede, Sari, additional, Krivoshik, Andrew, additional, and Humerickhouse, Rod, additional

Published
2009
Full Text
View/download PDF

21. An Ongoing Phase 1 Study of ABT-263; Pharmacokinetics, Safety and Anti-Tumor Activity in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

Author

Roberts, Andrew W., primary, Brown, Jennifer, primary, Seymour, John F., primary, Wierda, William G., primary, Kipps, Thomas J., primary, Xiong, Hao, primary, Chiu, Yi-Lin, primary, Busman, Todd, primary, Knight, Raymond A., primary, Enschede, Sari, primary, Krivoshik, Andrew, primary, and Humerickhouse, Rod, primary

Published
2008
Full Text
View/download PDF

22. Phase 1 Study of ABT-263, a Bcl-2 Family Inhibitor, in Relapsed or Refractory Lymphoid Malignancies.

Author

Wilson, Wyndham H, primary, O’Connor, O., primary, Czuczman, Myron S., primary, LaCasce, Ann, primary, Gerecitano, J., primary, Leonard, John P., primary, Tulpule, Anil, primary, Xiong, Hao, primary, Chiu, Yi-Lin, primary, Busman, Todd, primary, Knight, Raymond A., primary, Enschede, Sari, primary, Krivoshik, Andrew, primary, and Humerickhouse, Rod, primary

Published
2008
Full Text
View/download PDF

23. Impact of Number of Prior Therapies and Bulk of Disease on Outcomes with Venetoclax (VEN) Monotherapy for Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)

Author

Wierda, William G, Seymour, John F, Roberts, Andrew W., Kim, Su Young, Lash-Fleming, L. Leanne, Maher, Johnathan, Busman, Todd, Zhou, Lang, Nielsen, Jacqueline, and Stilgenbauer, Stephan

Abstract

Background:The BCL-2 inhibitorVEN is an effective therapy for patients (pts) with relapsed/refractory (R/R) CLL, including those with 17p deletion (del[17p]), a high-risk poor prognosis group. Historic reports with chemoimmunotherapy (CIT) demonstrated that less disease bulk, fewer lines of therapy, and sensitivity to chemotherapy correlated with depth and durability of remission. Here, we conducted a pooled analysis from 3 ongoing studies of VEN monotherapy to evaluate the impact of disease bulk and number of prior therapies on responses and outcomes.

Published
2017
Full Text
View/download PDF

24. Bcl-2 Inhibitor ABT-199 (GDC-0199) Monotherapy Shows Anti-Tumor Activity Including Complete Remissions In High-Risk Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)

Author

Seymour, John F., Davids, Matthew S., Pagel, John M., Kahl, Brad S., Wierda, William G., Miller, Thomas P., Gerecitano, John F., Kipps, Thomas J., Anderson, Mary-Ann, Huang, David C.S., Rudersdorf, Nikita K., Gressick, Lori A., Montalvo, Nicholas P., Yang, Jianning, Busman, Todd A., Dunbar, Martin, Cerri, Elisa, Enschede, Sari H., Humerickhouse, Rod A., and Roberts, Andrew W.

Abstract

Novel agents are needed for CLL/SLL patients (pts) R/R to standard therapies. The intrinsic apoptotic pathway is often dysregulated in relapsed CLL/SLL due to a deficiency in pro-apoptotic proteins such as TP53 and overexpression of anti-apoptotic proteins such as Bcl-2. ABT-199 is a selective, potent, orally bioavailable, small molecule Bcl-2 inhibitor that can trigger apoptosis in vitro, even in del(17p) CLL cells, making it a promising agent for the treatment of pts with CLL/SLL.The primary objectives of this phase I, dose-escalation study were to evaluate the safety, pharmacokinetics (PK), determine a maximum tolerated dose, and a recommended phase 2 dose of ABT-199. Secondary objectives were to assess efficacy and to explore biomarkers for response. Pts received a single dose of ABT-199 on Week1 Day -3 or -7 (W1D-3, W1D-7), followed by continuous once-daily dosing from W1D1, until disease progression or unacceptable toxicity. Modifications were made to the dose escalation scheme and tumor lysis syndrome (TLS) prophylaxis and monitoring schedule after TLS was observed in some pts. Evaluations included adverse events (AE; NCI-CTCAE-V4), Cairo-Bishop definitions of laboratory and clinical TLS, PK parameters and response.As of July 4, 2013, 56 pts were enrolled in cohorts at doses from 150 to 1200 mg, with a median time on study of 10.0 months (range 0-21.0). 17 (38%) pts had del(17p) and 18 (32%) had fludarabine (F)-refractory disease. 12 of 27 (44%) pts had beta-2 microglobulin levels >3 mg/L and 20 of 24 (83%) had IGVH unmutated status. 22 pts discontinued (D/C) ABT-199: 8 due to AEs, 12 due to progressive disease, 2 for other reasons (1 had a pulmonary embolus requiring Coumadin and 1 went to transplant in response). The most common AEs (All grades, ≥25% pts) were diarrhea (46%), neutropenia (43%), fatigue (34%), upper respiratory tract infection (29%), and cough (25%). Grade (G) 3/4 AEs occurring in ≥4 pts were neutropenia (41%), TLS (11%), thrombocytopenia (10%), hyperglycemia (10%), anemia (7%), and febrile neutropenia (7%). 7 DLTs have occurred to date: 5 TLS (1 G3 laboratory at 50 mg; 1 G4 clinical at 50 mg; 1 G3 laboratory at 100 mg and 2 at 200 mg); 1 G4 neutropenia (600 mg); and sudden death (1200 mg) in the setting of G4 (clinical) TLS. After a single dose of ABT-199 with food, Tmax and T1/2 values were approximately 6 and 17 hrs, respectively, supporting daily dosing. Preliminary efficacy data are summarized in the table below. In pts achieving CR/CRi, minimal residual disease (MRD) was quantified with 4 color flow cytometry using local lab methods (aiming to analyze >200,000 nucleated cells) and interpretation. 8 pts have evaluable results with no detectable MRD in 4 (2 with suboptimal cells analyzed) and low level MRD was found in 4 (0.05, 0.7, 0.75%; quantification pending in 1). Of the pts who had no detectable MRD, 1 pt was F-refractory and del(17p) and 2 pts were F-refractory.ABT-199 showed activity in pts with R/R CLL with a response rate of 84% for the study population, including 20% CR/CRi. Pts with high-risk CLL showed similar efficacy with a response rate of 82% in del(17p) and 78% in F-refractory disease. Notably, 3 of the 4 pts who had no detectable MRD and achieved a CR/CRi were high-risk disease pts. This study is continuing enrollment using a revised dosing schedule designed to reduce the identified risk of TLS. A phase 2 monotherapy study in pts with relapsed del(17p) CLL has commenced as well as combination studies with either rituximab or obinutuzumab in pts with relapsed CLL.Seymour Genentech: Consultancy, Membership on an entity’s Board of Directors or advisory committees. Kahl:AbbVie, Inc.: Research Funding; Genentech: Consultancy, Research Funding. Wierda:AbbVie, Inc.: Research Funding; Genentech: Consultancy, Research Funding, Speakers Bureau. Gerecitano:AbbVie: Research Funding; Genentech: Research Funding. Kipps:AbbVie, Inc.: Consultancy, Research Funding. Anderson:AbbVie, Inc.: Research Funding; Genentech: Research Funding; Walter and Eliza Hall Institute of Medical Research: Employee, which recieves commercial income related to ABT-199, Employee, which recieves commercial income related to ABT-199 Other. Huang:AbbVie, Inc.: Research Funding; Genentech: Research Funding; Walter and Eliza Hall Institute of Medical Research: Employee, recieves commercial income related to ABT-199, Employee, recieves commercial income related to ABT-199 Other, Employment. Rudersdorf:AbbVie, Inc.: Employment, Stock Other. Gressick:AbbVie, Inc: Employment, Stock Other. Montalvo:AbbVie, Inc.: Employment, Stock Other. Yang:AbbVie, Inc.: Employment, Stock Other. Busman:AbbVie, Inc.: Employment, Stock Other. Dunbar:AbbVie, Inc.: Employment, Stock Other. Cerri:AbbVie, Inc.: Employment, Stock Other. Enschede:AbbVie, Inc.: Employment, Stock Other. Humerickhouse:AbbVie, Inc.: Employment, Stock Other. Roberts:AbbVie, Inc.: Research Funding; Genentech: Research Funding; Walter and Eliza Hall Institute of Medical Research: Employee, recieves commercial income related to ABT-199, Employee, recieves commercial income related to ABT-199 Other, Employment.

Published
2013
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results