New Developments in Cancer Immunotherapy Among Major Tower Cancer Research Foundation Grants To Be Announced at Gala Honoring Philanthropists Meryl & Russell Kern, Shelley and Jan Rosen, and Steven Spielberg Family Chair in Hematology Oncology at Ce
News Article | April 27, 2017
LOS ANGELES, April 27, 2017 /PRNewswire/ -- Leaders in entertainment, politics, business and medicine will gather at Tower Cancer Research Foundation's Tower of Hope Gala on Thursday, May 4, 2017 to honor Meryl and Russell Kern, Dr. Robert Figlin and Shelley and Jan Rosen for their...
Verstovsek S.,University of Houston |
Verstovsek S.,University of Pavia |
Passamonti F.,Ospedali di Circolo e Fondazione Macchi Varese |
Rambaldi A.,Hematology and Bone Marrow Transplant Unit |
And 14 more authors.
Cancer | Year: 2014
BACKGROUND Polycythemia vera (PV) is a myeloproliferative neoplasm associated with somatic gain-of-function mutations of Janus kinase-2 (JAK2). Therapeutic options are limited in patients with advanced disease. Ruxolitinib, an oral JAK1/JAK2 inhibitor, is active in preclinical models of PV. The long-term efficacy and safety of ruxolitinib in patients with advanced PV who are refractory or intolerant to hydroxyurea were studied in a phase 2 trial. METHODS Response was assessed using modified European LeukemiaNet criteria, which included a reduction in hematocrit to < 45% without phlebotomy, resolution of palpable splenomegaly, normalization of white blood cell and platelet counts, and reduction in PV-associated symptoms. RESULTS Thirty-four patients received ruxolitinib for a median of 152 weeks (range, 31 weeks-177 weeks) or 35.0 months (range, 7.1 months-40.7 months). Hematocrit < 45% without phlebotomy was achieved in 97% of patients by week 24. Only 1 patient required a phlebotomy after week 4. Among patients with palpable splenomegaly at baseline, 44% and 63%, respectively, achieved nonpalpable spleen measurements at weeks 24 and 144. Clinically meaningful improvements in pruritus, night sweats, and bone pain were observed within 4 weeks of the initiation of therapy and maintained with continued treatment. Ruxolitinib treatment also reduced elevated levels of inflammatory cytokines and granulocyte activation. Thrombocytopenia and anemia were the most common adverse events. Thrombocytopenia of ≥ grade 3 or anemia of ≥ grade 3 (according to National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0) occurred in 3 patients each (9%) (1 patient had both) and were managed with dose modification. CONCLUSIONS Ruxolitinib was generally well tolerated and provided rapid and durable clinical benefits in patients with advanced PV who were refractory or intolerant to hydroxyurea. Cancer 2014;120:513-20. © 2013 The Authors published by Wiley Periodicals, Inc. on behalf of American Cancer Society. In the current study, patients with polycythemia vera who were refractory or intolerant to hydroxyurea achieved clinically meaningful and durable benefit from treatment with ruxolitinib with respect to reductions in hematocrit, platelet and white blood cell counts, splenomegaly, and symptoms. Given the limited therapeutic options for patients with advanced polycythemia vera, these results suggest that ruxolitinib has the potential to address an important unmet medical need in this patient population. © 2013 The Authors published by Wiley Periodicals, Inc. on behalf of American Cancer Society.
Chiappori A.,H. Lee Moffitt Cancer Center and Research Institute |
Williams C.,Arlington Cancer Center |
Northfelt D.W.,Mayo Clinic Arizona |
Adams J.W.,Arlington Cancer Center |
And 6 more authors.
Journal of Thoracic Oncology | Year: 2014
INTRODUCTION: The proapoptotic small-molecule pan-Bcl-2 inhibitor obatoclax mesylate (GX15-070) may enhance the cytotoxicity of chemotherapy in relapsed/refractory non-small-cell lung cancer (NSCLC). METHODS: Obatoclax was administered with docetaxel in patients with relapsed or refractory NSCLC - docetaxel as a 1-hour infusion on day 1 and obatoclax as a 24-hour infusion on days 1 and 2 - every 3 weeks for up to eight cycles. Four dose levels were evaluated in phase 1 (level 1: docetaxel 55 mg/m × 1 and obatoclax 30 mg × 2; levels 2-4: docetaxel 75 mg/m and obatoclax 30 mg, 45 mg, or 60 mg × 2) to identify dose-limiting toxicity and a phase 2 dose. In phase 2, response and tolerability were evaluated. RESULTS: Eighteen patients were included in phase 1. Two dose-limiting toxicities occurred during cycle 1: one febrile neutropenia each at dose levels 3 and 4. Maximum tolerated dose was not reached; 32 patients (including 3 from phase 1) were treated in phase 2 with docetaxel 75 mg/m and obatoclax 60 mg (median 2 cycles). Three patients (11%) had partial responses in phase 2; two demonstrated stable disease lasting 12 weeks or more. Median duration of response was 4.8 months. Overall, median progression-free survival was 1.4 months. Neutropenia (31%), febrile neutropenia (16%), and dyspnea (19%) were the most common grade 3/4 adverse events observed. CONCLUSIONS: Combined obatoclax mesylate plus docetaxel is tolerable in patients with NSCLC, but response was minimal and neutropenia was a common adverse event. Copyright © 2013 by the International Association for the Study of Lung Cancer.
Alsina M.,University of South Florida |
Trudel S.,University of Toronto |
Furman R.R.,New York Medical College |
Rosen P.J.,Tower Cancer Research Foundation |
And 6 more authors.
Clinical Cancer Research | Year: 2012
Purpose: Carfilzomib is a next-generation, selective, proteasome inhibitor with clinical activity in relapsed and/or refractory multiple myeloma. The objectives of this phase I study were to establish the safety, tolerability, pharmacokinetic, and pharmacodynamic profiles of escalating doses of carfilzomib in patients with relapsed or refractory hematologic malignancies. Experimental design: Carfilzomib (doses ranging from 1.2-27 mg/m2) was administered i.v. on 2 consecutive days for 3 weeks of a 4-week cycle. Single-agent dose escalation (n=37) was followed by a dose-expansion phase (n = 11) that comprised 2 cohorts (carfilzomib or carfilzomib + dexamethasone). During dose expansion, carfilzomib was administered starting with 20 mg/m 2 during the first week (days 1, 2) and then escalated to 27 mg/m2 thereafter. Results: A maximum tolerated dose (MTD) was not reached during dose escalation. Dosing in the expansion cohort was well tolerated. Adverse events were manageable and primarily of grade I or II. The main hematologic adverse events of ≥ grade III were anemia and thrombocytopenia. Notably, there were no observations of grade III or more peripheral neuropathy. Carfilzomib was cleared rapidly with an elimination half-life of less than 30 minutes but still induced dose-dependent inhibition of the 20S chymotrypsin-like proteasome activity. At doses of 15 to 27 mg/m 2, there was evidence of activity among patients with multiple myeloma and with non-Hodgkin lymphoma. Conclusions: Escalated dosing of carfilzomib on a schedule of 2 consecutive days for 3 weeks of a 4-week cycle was tolerable and showed promising activity. This dose regimen has been selected for ongoing and future clinical studies, including PX-171-003A1 and the pivotal trial ASPIRE. ©2012 AACR.
Vacirca J.L.,North Shore Hematology and Oncology Associates |
Acs P.I.,Florida Cancer Specialists |
Tabbara I.A.,George Washington University |
Rosen P.J.,Providence Saint Joseph Medical Center |
And 2 more authors.
Annals of Hematology | Year: 2014
Patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) are treated with salvage regimens and may be considered for high-dose chemotherapy and autologous stem cell transplantation if disease is chemosensitive. Bendamustine is active in indolent B cell lymphomas and chronic lymphocytic leukemia but has not been extensively studied in aggressive lymphomas. This trial examines the combination of bendamustine and rituximab in patients with relapsed and refractory DLBCL. Patients received bendamustine at 90 mg/m2 (n = 2) or 120 mg/m2 (n = 57) on days 1 and 2 and rituximab at 375 mg/m2 on day 1 every 28 days for up to 6 cycles. The study evaluated objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and treatment safety. Fifty-nine patients were treated, and 48 were evaluable for response. Median age was 74; 89 % had stage III or IV disease, and 63 % had high revised International Prognostic Index scores; the median number of prior therapies was 1. Based on analysis using the intent-to-treat population, the ORR was 45.8 % (complete response, 15.3 %; partial response, 30.5 %). The median DOR was 17.3 months, and the median PFS was 3.6 months. Grade 3 or 4 hematological toxicities included neutropenia (36 %), leukopenia (29 %), thrombocytopenia (22 %), and anemia (12 %). The combination of bendamustine and rituximab showed modest activity in patients with relapsed and refractory DLBCL and has an acceptable toxicity profile. © 2013 The Author(s).
Vij R.,University of Washington |
Wang M.,University of Texas M. D. Anderson Cancer Center |
Kaufman J.L.,Emory University |
Lonial S.,Emory University |
And 21 more authors.
Blood | Year: 2012
Carfilzomib is a selective proteasome inhibitor that binds irreversibly to its target. In phase 1 studies, carfilzomib elicited promising responses and an acceptable toxicity profile in patients with relapsed and/or refractory multiple myeloma (R/R MM). In the present phase 2, multicenter, open-label study, 129 bortezomibnaive patients with R/R MM (median of 2 prior therapies) were separated into Cohort 1, scheduled to receive intravenous carfilzomib 20 mg/m2 for all treatment cycles, and Cohort 2, scheduled to receive 20 mg/m2 for cycle 1 and then 27 mg/m2 for all subsequent cycles. The primary end point was an overall response rate (≥ partial response) of 42.4% in Cohort 1 and 52.2% in Cohort 2. The clinical benefit response (overall response rate + minimal response) was 59.3% and 64.2% in Cohorts 1 and 2, respectively. Median duration of response was 13.1 months and not reached, and median time to progression was 8.3 months and not reached, respectively. The most common treatment-emergent adverse events were fatigue (62.0%) and nausea (48.8%). Single-agent carfilzomib elicited a low incidence of peripheral neuropathy - 17.1% overall (1 grade 3; no grade 4) - in these pretreated bortezomib-naive patients. The results of the present study support the use of carfilzomib in R/R MM patients. This trial is registered at www.clinicaltrials.gov as NCT00530816. © 2012 by The American Society of Hematology.
Lee P.P.,Tower Cancer Research Foundation |
Rosen P.J.,Roy and Patricia Disney Family Cancer Center
Community Oncology | Year: 2011
Radioimmunotherapy (RIT) using CD20-targeted immunoconjugates remains a viable option for patients with non-Hodgkin's lymphoma (NHL). In addition, the use of RIT as a consolidation therapy is an appealing strategy, given the short course of well-tolerated regimens. The two available RIT agents-yttrium-90 ibritumomab and iodine-131 tositumomab-have undergone extensive trials leading to specific approvals for certain categories of indolent NHL. Despite their apparent utility, these drugs have been underutilized for a variety of reasons, including the somewhat complex process of drug delivery, concerns about possible late toxicities, and economic factors. In this article, the authors review the data supporting the label indications for use of these agents and discuss potentially interesting off-label uses of these drugs as well. © 2011 Elsevier Inc. All rights reserved.
Rosen P.J.,Tower Cancer Research Foundation |
Sweeney C.J.,Indiana University |
Park D.J.,Tower Cancer Research Foundation |
Beaupre D.M.,Amgen Inc. |
And 7 more authors.
Clinical Cancer Research | Year: 2010
Purpose: This phase Ib study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of AMG 102, a fully human monoclonal antibody against hepatocyte growth factor/scatter factor (HGF/SF), in combination with bevacizumab or motesanib in patients with advanced solid tumors. Experimental Design: Patients with treatment-refractory advanced solid tumors were sequentially enrolled into four cohorts (3, 10, or 20 mg/kg AMG 102 plus 10 mg/kg bevacizumab i.v. every 2 weeks, or 3 mg/kg AMG 102 i.v. every 2 weeks plus 75 mg motesanib orally once daily). Results: Fourteen patients were enrolled and received AMG 102. The combination of AMG 102 with bevacizumab (n = 12) seemed to have acceptable toxicity. The number of patients (n = 2) who received AMG 102 plus motesanib was insufficient to adequately assess safety. No dose-limiting toxicities were reported. Enrollment in the motesanib cohort was suspended because of reports of cholecystitis in other motesanib studies. Treatment-emergent adverse events among patients receiving AMG 102 plus bevacizumab were generally mild and included fatigue (75%), nausea (58%), constipation (42%), and peripheral edema (42%). No anti-AMG 102 antibodies were detected. Bevacizumab did not seem to affect AMG 102 pharmacokinetics. Circulating total HGF/SF increased from baseline throughout the study. Eight of 10 evaluable patients had reductions in tumor dimensions, and stable disease at ≥8, ≥16, and ≥24 weeks occurred in 9, 7, and 4 patients, respectively. Progression-free survival ranged from 7.9 to 121.9 weeks. Conclusions: AMG 102 in combination with bevacizumab was well tolerated. Further evaluation of AMG 102 in combination with antiangiogenic agents is warranted. ©2010 AACR.
Weinreb N.J.,Boca Research |
Finegold D.N.,Childrens Hospital of Pittsburgh |
Feingold E.,University of Pittsburgh |
Zeng Z.,University of Pittsburgh |
And 3 more authors.
Orphanet Journal of Rare Diseases | Year: 2015
Background: GD1-DS3 is an integrated assessment of type 1 Gaucher disease (GD1) burden based on bone, hematologic and visceral domains. We investigated this disease severity scoring system (DS3) methodology for initial assessment, long-term follow-up and evaluation of treatment responses. Methods: We enrolled 133 treated adult GD1 patients. Baseline DS3 scores were calculated near the initial treatment date and patients stratified by severity as marked (DS3 6.00-19.00), moderate (DS3 3.00-5.99), mild (DS3 < 3.00). Follow-up scores were calculated annually. Minimal clinically important improvement (MCII), is defined as ΔDS3 of -3.1. Results: Patient characteristics: N370S was the most common allele (118 patients had at least one), 52 were N370S/N370S (48/52 were Ashkenazi Jews), N370S/L444P was the most common genotype among non-Jews. Median age of treatment: 45 years; median follow-up: 14 years. Baseline DS3 scores: Patients with marked disease (N = 58; median 7.84) were least likely to be N370S homozygous (19 %) and most likely to have had splenectomy (53 %), early age at diagnosis (median 18 years) and major pre-treatment bone pathology (76 %). Among patients with moderate disease (N = 53; median 4.33), 49 % were N370S/N370S, 15.1 % had splenectomy and 17 % had major bone disease. Median age at diagnosis: 32 years. No patient with mild disease (N = 22; median 2.4) had splenectomy or major skeletal disease. Median age at diagnosis: 40 years. 68 % were N370S homozygous. Response to treatment: Health-state transitions occurred primarily during the early treatment years. At Year 5, among 48 evaluable patients with marked baseline disease, eight were unchanged in severity status whereas 40 had MCII of varying degrees with 11 scored as mild. Among 42 evaluable moderate patients, none worsened, 16 remained moderate and 26 improved to mild. Among 16 evaluable mild patients, 14 remained so and 2 had DS3 scores in the low moderate range. Conclusions: DS3 is effective for assessing disease burden in GD1 and for monitoring response. ERT was associated with MCII in DS3 scores in patients with high severity. Nevertheless, despite better DS3 scores with treatment, GD1 patients especially those with splenectomy and pre-treatment bone pathology, continued to have bone complications. © 2015 Weinreb et al.
PubMed | Amgen Inc., University of Washington, University of Houston and Tower Cancer Research Foundation
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2017
41 Background: AMG 208 is a small molecule MET inhibitor that suppresses proliferation and induces apoptosis in human tumor xenografts. This first-in-human study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of AMG 208. We report data from the dose escalation part of the study.Key eligibility criteria: 18 yr, advanced solid tumors, ECOG 2, and evaluable/measurable disease. Using a modified Fibonacci design, 3-9 pts were enrolled into 1 of 7 sequential dose cohorts (25, 50, 100, 150, 200, 300, and 400 mg) of AMG 208. Pts received AMG 208 orally on days 1 and 4-28 once daily. If no dose limiting toxicity (DLT) was seen on days 1-28, pts received AMG 208 once daily starting at day 36 provided pts showed no evident disease progression. In cohorts 1-3, a standard 3+3 design was followed. In cohorts 4-7, a modified 3+3+3 design was followed.As of July 16 2012, 54 pts (25 mg [n=6], 50 mg [n=4], 100 mg [n=4], 150 mg [n=3], 200 mg [n=16], 300 mg [n=10], and 400 mg [n =11]) had received 1 dose of AMG 208. 67% were men; 19% had prostate cancer (PC). Median (range) age: 61 (39-80) yr. ECOG 0/1: 52%/48%. 6 DLTs were seen: a grade (G) 3 increased AST (200 mg), a G3 thrombocytopenia (200 mg), a G4 acute myocardial infarction (300 mg), a G3 prolonged QT (300 mg), and two G3 hypertensions (400 mg). The maximum tolerated dose was not reached. 83% of pts had tx-related adverse events (AE). Tx-related AE occurring in > 10 pts: fatigue (n=24), nausea (n=18), hypertension (n=12), and diarrhea (n=11). 24% of pts had grade 3 tx-related AE. AMG 208 was orally bioavailable with a 30-35 hr mean half-life in plasma. Exposure increased linearly with dose; accumulation at day 28 was 2.7-fold across cohorts. Of the 42 pts with available tumor response data for site reads, 1 had complete response on bone scan (PC 300 mg) while 2 had partial responses (PR; PC 400 mg and kidney cancer 200 mg; both had -33% tumor shrinkage), and 29 had stable disease (SD); 1 other PC pt had PR after data cutoff. Of the 35 pts with available tumor response data for central reads, 26 had SD. FLT and biomarker data will be presented.AMG 208 up to 400 mg daily had manageable toxicities and showed evidence of antitumor activity, especially in prostate cancer.NCT00813384.