scholarly journals Efficacy of Brentuximab Vedotin in Relapsed or Refractory High-CD30–Expressing Non-Hodgkin Lymphomas: Results of a Multicenter, Open-Labeled Phase II Trial

2020 ◽  
Vol 52 (2) ◽  
pp. 374-387 ◽  
Author(s):  
Seok Jin Kim ◽  
Dok Hyun Yoon ◽  
Jin Seok Kim ◽  
Hye Jin Kang ◽  
Hye Won Lee ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Disease Control ◽  
Phase Ii ◽  
Single Agent ◽  
Survival Rates ◽  
Sensory Neuropathy ◽  
Large Cell ◽  
Brentuximab Vedotin ◽  
Disease Control Rate ◽  
Wide Range

PurposeThe treatment outcome of brentuximab vedotin (BV) has not been related with CD30 expression in previous studies enrolling patients with a wide range of CD30 expression level. Thus, this study explored the efficacy of BV in high-CD30–expressing non-Hodgkin lymphoma (NHL) patients most likely to benefit.Materials and MethodsThis phase II study (Clinicaltrials.gov: NCT02280785) enrolled relapsed or refractory high-CD30–expressing NHL, with BV administered intravenously at 1.8 mg/kg every 3 weeks. The primary endpoint was > 40% disease control rate, consisting of complete response (CR), partial response (PR), or stable disease. We defined high CD30 expression as ≥ 30% tumor cells positive for CD30 by immunohistochemistry.ResultsHigh-CD30-expressing NHL patients (n=33) were enrolled except anaplastic large cell lymphoma. The disease control rate was 48.5% (16/33) including six CR and six PR; six patients (4CR, 2PR) maintained their response over 16 completed cycles. Response to BV and survival were not associated with CD30 expression levels. Over a median of 29.2 months of follow-up, the median progression-free and overall survival rates were 1.9 months and 6.1 months, respectively. The most common adverse events were fever (39%), neutropenia (30%), fatigue (24%), and peripheral sensory neuropathy (27%). In a <i>post-hoc</i> analysis for the association of multiple myeloma oncogene 1 (MUM1) on treatment outcome, MUM1- negative patients showed a higher response (55.6%, 5/9) than MUM1-positive patients (13.3%, 2/15).ConclusionBV performance as a single agent was acceptable in terms of disease control rates and toxicity profiles, especially MUM1-negative patients.

Phase II trial of oxaliplatin, pemetrexed, and bevacizumab in previously-treated advanced non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7700-7700 ◽  
Author(s):  
R. S. Heist ◽  
P. Fidias ◽  
M. Huberman ◽  
J. Temel ◽  
L. Sequist ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Sensory Neuropathy ◽  
Large Cell ◽  
Study Patient ◽  
Eligibility Criteria ◽  
Grade Iii

7700 Background: Single agent chemotherapy is standard for second and third line therapy of NSCLC. Combination therapy has to date not proven to be superior to single agents –often adding additional toxicity without any additional efficacy. We investigated whether the combination of oxaliplatin, pemetrexed, and bevacizumab was an active and tolerable regimen in the pre-treated advanced NSCLC setting. Methods: In this two-stage phase II trial, patients received pemetrexed (500 mg/m2), oxaliplatin (120 mg/m2), and bevacizumab (15 mg/kg) on day 1 of every 21 day cycle, for a total of 6 cycles or until disease progression. Eligibility criteria included PS 0–1, non-squamous histology, and at least one prior chemotherapy regimen. Patients with treated brain metastases were allowed on this trial. The primary endpoint was response rate, with secondary endpoints of TTP, PFS, and OS. Results: 36 patients were enrolled on this study. Patient characteristics for 32 for which data is available were: 16 (50%) women, 16 (50%) men, 26 (81%) adenocarcinoma, 6 (19%) large cell or NSCLC, 6 (19%) treated brain metastases. Of the 31 patients evaluable for tumor response, 0 had CR, 8 (25%) had PR, 14 (44%) had SD, and 9 (28%) had PD. One patient experienced Grade V hemoptysis after cycle 2 before restaging. Nine patients experienced a Grade III/IV serious adverse event. These Grade III/IV toxicities included: cardiac ischemia (1), sensory neuropathy (1), dyspnea (1), anemia (1), constipation (1), fatigue (1), colitis (1), face pain (1), hyperglycemia (1), elevated ALT (1). Among the 6 patients with treated brain metastases, there was 1 PR, 2 SD, 2 PD, and one patient with Grade V hemoptysis whose response could not be assessed; there were no brain hemorrhage events. Data for PFS and OS are preliminary; estimated median PFS is 5.8 months (95% CI 3.8 - 8.9 mo), and estimated OS is 10.9 mo (95% CI 6.4 - 20 mo). Updated data will be presented at the time of the meeting. Conclusions: This data suggests that the combination of pemetrexed, oxaliplatin, and bevacizumab is tolerable and has a promising response rate. Updated data will be presented at the meeting. No significant financial relationships to disclose.

scholarly journals Brentuximab Vedotin (BV) and Lenalidomide (Len) in Relapsed and Refractory (r/r) Cutaneous (CTCL) and Peripheral (PTCL) T-Cell Lymphomas; A Planned Interim Analysis of Phase II Trial

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2853-2853
Author(s):  
Basem M. William ◽  
Ying Huang ◽  
Amy Johnson ◽  
Jonathan E Brammer ◽  
John C. Reneau ◽  
...  
Keyword(s):  
T Cell ◽  
Board Of Directors ◽  
Phase Ii ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Single Agent ◽  
Large Cell ◽  
Median Number ◽  
Brentuximab Vedotin ◽  
Advisory Committees

Background: Patients with r/r tumor stage CTCL and/or PTCL have a poor prognosis. BV is currently FDA approved for CD30 positive CTCL and anaplastic large cell lymphoma (ALCL) with single agent activity in additional PTCL subtypes. Len also has single agent activity in patients with r/r CTCL/PTCL. The safety of the combination was established in a phase I trial in patients with r/r diffuse large B-cell lymphoma. Methods: We conducted a single-institution phase II trial to determine the safety and efficacy of BV+Len combination in patients with r/r CTCL/PTCL. Simon's 2-stage optimal design was followed to test the null hypothesis of overall response rate (ORR) ≤0.3 versus the alternative hypothesis of ORR≥0.5. Patients with ≥ 1 line of systemic therapy or 2 lines of skin directed therapy, at least stage IB (for CTCL), and no prior progression on BV were eligible regardless of CD30 staining. All patients were treated with BV 1.2 mg/kg IV and Len 20 mg PO daily q3 weeks for a maximum 16 cycles. After 7 patients were treated, we reduced Len to 10 mg given safety/tolerability concerns. Responses are assessed by the International Society for Cutaneous Lymphomas and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (ISCL/EORTC) Global response criteria (for CTCL) and Cheson year criteria (for PTCL). The effect of treatment on quality of life is assessed by Skindex-16. Results: As of July 1, 2019, 17 subjects were treated; 10 (59%) with mycosis fungoides (MF), 2 (12%) with Sezary syndrome (SS), 2 (12%) with CD30+ lymphoproliferative disorder, and 3 (18%) with PTCL. Median age was 60 (49-90) years and 76% were males. CD30 was completely negative (<1%) in 3 (18%) of patients and median CD30 staining (by immunohistochemistry) was 7.5% (range 1-75%). Of 12 patients with MF/SS, 5 (42%) had evidence of large cell transformation at accrual. Of 14 patients with CTCL, median baseline mSWAT was 54.5 (range 4.4-190). Median number of prior therapies was 5 (range 1-9). Grade 3 adverse events (AEs) were reported in 11/17 patients; including neutropenia (4), thrombocytopenia (1), bronchitis (1), dyspnea (1), abdominal pain (2), vertigo (1), , DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) syndrome (1), urinary tract infection (1), and tumor flare (2). Median number of cycles received was 4 (range 1-17). Best response in 14 evaluable patients were 2 (14%) complete response, 3 (21%) partial response, and 8 (57%) stable disease with ORR of 33% (95% confidence interval:12-62%). Of 17 patients, 5 (29%) remain on treatment, and 12 (71%) discontinued treatment because of disease progression (7; 58%), AEs (4; 33%), or patient preference (1; 2%). Median duration of response was 3.2 (range 2.5-13) months. Of note, 7/14 patients (50%) patients with CTCL had >50% reduction in their Skindex-16 scores after a median of 2 cycles (range 1-3). Conclusions: BV + Len is combination is safe and efficacious in a heavily pre-treated patients with T-cell lymphomas. Len doses higher than 10 mg daily are poorly tolerated and associated with excess tumor flare. Recruitment of both CTCL and PTCL patients for this trial is ongoing. Disclosures William: Guidepoint Global: Consultancy; Kyowa Kirin, Inc.: Consultancy; Defined Health: Consultancy; Techspert: Consultancy; Celgene Corporation: Consultancy. Brammer:Verastem, Inc: Research Funding; Viracta Therapeutics, Inc.: Research Funding; Bioniz Therapeutics, Inc.: Research Funding. Grantier:Pharmacyclics LLC and Janssen Oncology: Other: Advisory Board. Hoffman:Pharmacyclics LLC and Janssen Oncology: Other: Advisory Board. Baiocchi:Prelude: Consultancy. Epperla:Pharmacyclics: Honoraria; Verastem Oncology: Speakers Bureau. Christian:Triphase: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Immunomedics: Research Funding; Acerta: Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding; Cephalon: Research Funding; Merck: Research Funding; Janssen: Research Funding; Millennium Pharmaceuticals Inc: Research Funding. Maddocks:BMS: Research Funding; Merck: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Brentuximab vedotin is being used off-label for CD30 negative peripheral and cutaneous T-cell lymphoma. Lenalidomide is being used off-label for both conditions (within a phase II clinical trial)

scholarly journals Cediranib for Metastatic Alveolar Soft Part Sarcoma

2013 ◽  
Vol 31 (18) ◽  
pp. 2296-2302 ◽  
Author(s):  
Shivaani Kummar ◽  
Deborah Allen ◽  
Anne Monks ◽  
Eric C. Polley ◽  
Curtis D. Hose ◽  
...  
Keyword(s):  
Partial Response ◽  
Disease Control ◽  
Phase Ii ◽  
Stable Disease ◽  
Soft Part ◽  
Expression Profiles ◽  
Single Agent ◽  
Disease Control Rate ◽  
Alveolar Soft Part Sarcoma ◽  
Tumor Biopsies

Purpose Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor, for which no effective standard systemic treatment exists for patients with unresectable disease. Cediranib is a potent, oral small-molecule inhibitor of all three vascular endothelial growth factor receptors (VEGFRs). Patients and Methods We conducted a phase II trial of once-daily cediranib (30 mg) given in 28-day cycles for patients with metastatic, unresectable ASPS to determine the objective response rate (ORR). We also compared gene expression profiles in pre- and post-treatment tumor biopsies and evaluated the effect of cediranib on tumor proliferation and angiogenesis using positron emission tomography and dynamic contrast-enhanced magnetic resonance imaging. Results Of 46 patients enrolled, 43 were evaluable for response at the time of analysis. The ORR was 35%, with 15 of 43 patients achieving a partial response. Twenty-six patients (60%) had stable disease as the best response, with a disease control rate (partial response + stable disease) at 24 weeks of 84%. Microarray analysis with validation by quantitative real-time polymerase chain reaction on paired tumor biopsies from eight patients demonstrated downregulation of genes related to vasculogenesis. Conclusion In this largest prospective trial to date of systemic therapy for metastatic ASPS, we observed that cediranib has substantial single-agent activity, producing an ORR of 35% and a disease control rate of 84% at 24 weeks. On the basis of these results, an open-label, multicenter, randomized phase II registration trial is currently being conducted for patients with metastatic ASPS comparing cediranib with another VEGFR inhibitor, sunitinib.

Sequential Topoisomerase I (Topo I) and Topoisomerase II (Topo II) Inhibitors in Relapsed/Refractory Aggressive NHL: Results of CALGN 59906, a Phase II Study of Doxorubicin and Topotecan.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2500-2500 ◽  
Author(s):  
Sonali M. Smith ◽  
Jeffrey L. Johnson ◽  
Donna Niedzwiecki ◽  
J. Paul Eder ◽  
George P. Canellos ◽  
...  
Keyword(s):  
Phase Ii ◽  
Topoisomerase I ◽  
Phase Ii Study ◽  
Single Agent ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
Cell Transplant ◽  
Histologic Subtype ◽  
Sequential Administration ◽  
Topo Ii

Abstract Topoisomerase enzymes are critical components of genomic replication and function to minimize torsional stress on DNA. Inhibition of topoisomerase function leads to DNA strand breaks followed by apoptosis. In malignant lymphomas, topo II inhibitors (anthracyclines, epidophyllotoxins) are part of many active regimens, and topo I inhibitors (camptothecins) show modest single agent activity. Supported by preclinical data, we hypothesized that the sequential administration of a topo II inhibitor followed by a topo I inhibitor would be potentially synergistic, with enhanced cytotoxicity of the topo I inhibitor due to increased target enzyme levels following topo II inhibition. The treatment regimen consisted of doxorubicin 25 mg/m2 IV on day 1 and topotecan 1.75 mg/m2/d IV on days 3–5, repeated at 21 day intervals. The primary objective of this phase II study was to determine the overall response rate, time to progression, and toxicity in patients with relapsed/refractory aggressive NHL. Eligible patients had recurrent or refractory aggressive NHL, no prior camptothecins, and limited prior anthracycline exposure (<400 mg/m2 prior doxorubicin; <96 mg/m2 prior mitoxantrone), and an ejection fraction ≥ 45% at baseline. Results: From July 2000 to August 2003, 26 patients were registered. One registered patient did not start protocol treatment and is excluded from analysis. Of 22 patients with a known histologic subtype, 18 had diffuse large B cell lymphoma and there was one case each of Burkitt’s, follicular grade III, anaplastic large cell, and anaplastic large cell, Hodgkin’s like lymphoma. The median age was 58 (range 23–74) years. All patients were heavily pretreated with a median of 2 (range 1–5) prior regimens, including 5 patients who had a prior stem cell transplant (SCT). A median of 2 cycles (range 1–6) were administered. Five patients (20%, 95% CI 0.07, 0.42) responded with 1 (4%) complete remission (CR) and 4 (16%) partial remissions (PR); an additional 3 (12%) patients had stable disease. 12 (48%) patients progressed during or after the first cycle and 5 (20%) progressed after the second cycle. The one patient achieving a CR had Burkitt’s lymphoma, and received a total of 6 cycles; this patient remains in remission 21 months following the end of treatment. Of the PR patients, 2 remain in PR at 1.5 and 12 months following therapy, and 2 patients have progressed at 1.5 and 6 months. Interestingly, 4 of the 5 responders had prior SCT. The main toxicity was hematologic, with 14 (63%) and 9 (41%) patients having grade 3 or 4 neutropenia and thrombocytopenia, respectively. Three patients had febrile neutropenia. There were no treatment-related deaths. Seven patients remain alive and 18 patients have died. The median follow-up time for surviving patients is 14 (range 7–27) months. The median event-free survival is 1.3 months and the median overall survival is 3.6 months. The combination of doxorubicin and topotecan is well-tolerated and has modest activity in relapsed/refractory NHL, with an occasional patient having a prolonged remission.

The Telomerase Inhibitor, Imetelstat, Rapidly Reduces Myeloma Cancer Stem Cells (CSCs) in a Phase II Trial

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4898-4898 ◽  
Author(s):  
Carol Ann Huff ◽  
Quiju Wang ◽  
Ashraf Z. Badros ◽  
Richard J. Jones ◽  
Anita Reddy ◽  
...  
Keyword(s):  
Clinical Response ◽  
Disease Progression ◽  
Phase Ii ◽  
Single Agent ◽  
Stem Cell Marker ◽  
Self Renewal ◽  
Serial Measurement ◽  
Telomerase Inhibitor ◽  
Study Evaluation ◽  
Wide Range

Abstract Abstract 4898 Despite improved response rates with the use of novel agents, the vast majority of patients with multiple myeloma (MM) experience disease relapse and progression. This clinical pattern suggests the cells responsible for tumor regrowth persist following treatment, and we previously demonstrated that highly tumorigenic and self-renewing MM cells are relatively resistant to a wide range of anti-myeloma agents. These MM CSCs are present in the peripheral blood circulation and express memory B cell surface antigens (CD19 and CD27) and the stem cell marker aldehyde dehydrogenase (ALDH). We have also studied cellular mechanisms regulating self-renewal and found that MM CSCs express increased levels of telomerase activity (TA). In preclinical models, the novel telomerase inhibitor imetelstat has been found to inhibit CSCs from a wide range of tumor types, and we reported that imetelstat reduced TA in MM CSCs resulting in the loss of self-renewal and clonogenic growth potential. In an open label phase II clinical trial initiated in February 2011, previously treated MM patients (pts) (n=6) with stable but detectable disease following treatment with an iMid or proteasome inhibitor received single agent imetelstat (7.5–9.4 mg/kg IV on days 1 and 8 every 21–28 days). Additional pts (n=4) receiving lenalidomide maintenance and whose disease was stable for at least three months have also been enrolled. Pts received imetelstat therapy until evidence of disease progression or toxicity. Median age is 62.5 years (range 53–68); median number of prior therapies is 1 (range 1–4) including 4 pts with prior autologous transplant and 1 pt with prior mini-allogeneic transplant; 8 pts with prior bortezomib use; 9 pts with prior iMiD use; and 4 pts with concurrent lenalidomide use with receipt of lenalidomide for a median of 11.38 months (range 4.51–19.21 months) prior to initiation of imetelstat. As of July 30, 2012, 6 pts remain on study. Four pts were discontinued from imetelstat therapy after receiving a median of 7 doses of imetelstat either due to disease progression (n=2) or hematologic toxicity (n=2). Cytopenias were the most frequently reported toxicity with 8 of 10 pts demonstrating grade 3–4 thrombocytopenia and neutropenia during cycle 2, often requiring dose reductions or holds in subsequent cycles. The frequency of circulating MM CSCs (CD19+CD27+ALDH+) was quantified by flow cytometry. Circulating MM CSCs could be detected prior to the initiation of imetelstat (mean 10.7 × 10e3 cells/ml, range 17–53 × 10e3) in 8 of the 9 pts who have completed at least 2 cycles of treatment with imetelstat. In the single remaining patient, circulating CSCs were assessed from Cycle 2 onwards. Over the course of treatment, the frequency of MM CSCs decreased significantly, on average 2 fold every 30 days (Fig 1), in 8 of the 9 patients studied despite no upgrades in clinical response as per IWG criteria. In two pts who received 4 and 6 cycles of single agent imetelstat respectively, standard responses detected as decreasing or plateaued serum M protein or light chain levels were sustained over 4 months following discontinuation (Fig 2). Moreover, these delayed responses occurred in the absence of any additional therapy. These findings demonstrate that imetelstat rapidly decreases circulating MM CSCs. In addition, several patients experienced delayed, but sustained, clinical responses as measured by standard criteria. Therefore, imetelstat may have therapeutic implications for MM and other malignancies driven by CSCs. Figure 1. Serial measurement of CSCs in patients (n=9) treated with imetelstat Figure 1. Serial measurement of CSCs in patients (n=9) treated with imetelstat Figure 2. Clinical response in Pts 003 and 004 based on changes in paraprotein level. Dashed line represents off study evaluation. Figure 2. Clinical response in Pts 003 and 004 based on changes in paraprotein level. Dashed line represents off study evaluation. Disclosures: Huff: Celgene: Scientific Advisory Board Other; Novartis: Consultancy. Jones:Cytomedix: Royalties, Royalties Patents & Royalties. Reddy:Geron Corp.: Employment. Nishimoto:Geron Corp: Employment. Stuart:Geron Corp: Consultancy, Employment; OncoMed Pharmaceuticals: Consultancy. Kelsey:Geron Corp: Employment. Matsui:Geron Corp.: Research Funding.

A prospective multicenter phase II trial of capecitabine plus oxaliplatin (CapOx) in advanced biliary system adenocarcinomas: The final results

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4136-4136 ◽  
Author(s):  
O. Nehls ◽  
H. Oettle ◽  
J. Hartmann ◽  
R. Hofheinz ◽  
H. Hass ◽  
...  
Keyword(s):  
Disease Control ◽  
Survival Data ◽  
Sensory Neuropathy ◽  
Complete Response ◽  
Biliary System ◽  
Disease Control Rate ◽  
Eligibility Criteria ◽  
Grade 3 ◽  
Ecog Ps ◽  
Peripheral Sensory

4136 Background: To investigate the safety and efficacy of capecitabine and oxaliplatin combination therapy (CapOx) in unresectable or metastatic adenocarcinomas of the biliary system. Methods: 65 patients (pts) (27 male, and 38 female) were enrolled (median age, 61 yrs). Major eligibility criteria: histologically proven, measurable disease, age ≤ 75 yrs, ECOG PS 0–2. A total number of 364 cycles (median, 5; range, 1–16) of oxaliplatin (130 mg/m2, d1) plus capecitabine (2 g/m2, d 1–14) were administered 3 weekly for gallbladder carcinoma (GBC) (27 pts), extrahepatic (20 pts), and intrahepatic (18 pts) cholangiocarcinoma (CCC). Response rates were assessed according to WHO criteria. Clinical outcome was determined separately for pts with either GBC/extrahepatic CCC or intrahepatic CCC (mass-forming type). Results: Grade 4 toxicities (WHO): diarrhea in 1 pt (1% of cycles), thrombocytopenia in 1 pt (1%), leukocytopenia in 1 pt (1%), and fever in 2 pts (1%); grade 3 toxicities: nausea/vomiting in 1 pt (1%), diarrhea in 2 pts (1%), thrombocytopenia in 3 pts (2%), and fever in 1 pt (1%). Grade 3/4 peripheral sensory neuropathy (Lévis scale) was found in 13 pts (14% of cycles). Two pts were excluded from study because of oxaliplatin-related allergic reactions. One patient died due to sepsis and another due to cerebral insult during the first treatment cycle. The overall disease control rate in 47 pts with GBC or extrahepatic CCC was 72% (complete response (CR), n = 2 (4%); partial response (PR), n = 11 (23%); stable disease (NC), n = 21 (45%)), whereas progressive disease (PD) was found in 13 pts (28%). In 18 pts with intrahepatic mass-forming CCC, no CR or PR was observed, 5 pts (28%) had SD, and 13 pts (72%) experienced PD. Conclusions: The CapOx protocol is well tolerated and remarkably active for advanced GBC as well as extrahepatic CCC with a disease-control rate of 72%. However, activity appears to be limited in the subset of pts with intrahepatic mass-forming type tumors. Survival data will be presented at the meeting. No significant financial relationships to disclose.

FOLFIRI plus ramucirumab versus paclitaxel plus ramucirumab as second-line therapy for patients with advanced or metastatic gastroesophageal adenocarcinoma with or without prior docetaxel: Results from the phase II RAMIRIS Study of the AIO.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4514-4514 ◽  
Author(s):  
Sylvie Lorenzen ◽  
Peter C. Thuss-Patience ◽  
Claudia Pauligk ◽  
Eray Goekkurt ◽  
Thomas Jens Ettrich ◽  
...  
Keyword(s):  
Disease Control ◽  
Phase Ii ◽  
Response Rate ◽  
Objective Response ◽  
Disease Control Rate ◽  
Phase Iii ◽  
Response Analysis ◽  
Second Line ◽  
Significant Difference ◽  
Gastroesophageal Adenocarcinoma

4514 Background: Ramucirumab (Ram) as monotherapy or plus paclitaxel is a proven second-line option for advanced gastroesophageal adenocarcinoma (GEA). More and more patients (pts) are pretreated with docetaxel in the perioperative or first-line setting. These pts may benefit more from another, non-cross resistant chemotherapy backbone regimen. This trial evaluates the addition of Ram to FOLFIRI as second line treatment. Methods: This is a multicenter, randomized, investigator initiated, phase II trial. Pts with GEA who have progressed after treatment with a fluoropyrimidine/platinum-containing regimen were randomized 2:1 to either FOLFIRI plus Ram every two weeks (Arm A) or paclitaxel (days 1, 8, 15 of a 28-day cycle) plus Ram every two weeks (Arm B). Major endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), progression free survival (PFS) and toxicity. Results: 111 pts (median age 61 years, 65% of pts had prior docetaxel therapy) were enrolled and 110 analyzed within intention to treat population (ITT, Arm A, 72; Arm B, 38). In the ITT, there was no significant difference in median OS (A, 6.8 vs. B, 7.6 months, HR 0.94, p = 0.77) and median PFS (A, 4.6 vs. B, 3.6 months, HR 0.72, p = 0.12). For pts with prior docetaxel use (71/110), median PFS was A, 4.3 vs. B, 2.0 months, HR 0.49, p = 0.008 and median OS was A, 7.5 vs. B, 6.4 months, HR 0.71, p = 0.25. In 101 pts with tumor assessment and included in the response analysis, ORR and DCR was 23% and 65% in Arm A and 11% and 60% in Arm B, respectively. 67 pts assessable for response were pre-treated with docetaxel. In these pts, ORR was 24% in Arm A and 9% in Arm B. Disease control rate (DCR) was 67% and 41% for Arm A and B respectively. Both therapies were similarly tolerable, final safety results will be shown. Conclusions: The RAMIRIS trial demonstrated feasibility of the combination of FOLFIRI and Ram. With a response rate of 24% and a median PFS of 4.3 months, docetaxel pre-treated pts seemed to derive pronounced benefit from FOLFIRI-Ram, providing a rationale for a phase III trial, which is currently ongoing. Clinical trial information: NCT03081143 .

scholarly journals Ruxolitinib shows activity against Hodgkin lymphoma but not primary mediastinal large B-cell lymphoma

2019 ◽  
Author(s):  
Seok Jin Kim ◽  
Dok Hyun Yoon ◽  
Hye Jin Kang ◽  
Jung Yong Hong ◽  
Ho Sup Lee ◽  
...  
Keyword(s):  
Disease Control ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Cell Lymphoma ◽  
Single Agent ◽  
B Cell Lymphoma ◽  
Disease Control Rate ◽  
Median Response ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background The upregulated expression of the JAK/STAT pathway promotes tumor growth in Hodgkin lymphoma (HL) and primary mediastinal large B-cell lymphoma (PMBCL). Based on the hypothesis that JAK2 is a therapeutic target, we performed a prospective pilot study using ruxolitinib. Methods Relapsed or refractory patients with HL or PMBCL were eligible for this study, and JAK2 amplification was assessed by fluorescence in situ hybridization. Ruxolitinib was administered orally at a dose of 20 mg twice daily for a 28-day cycle. Treatment was continued for up to 16 cycles or until progressive disease or intolerability. The primary objective was to assess the overall disease control rate comprising complete response (CR), partial response (PR), or stable disease (SD). Results We analyzed 13 HL patients and six PMBCL patients. All responders (one CR, five PR, and one SD) had HL whereas all cases of PMBCL progressed after first or second cycle. The disease control rate for HL was 54% (7/13) with median response duration of 5.6 months. JAK2 amplification was present in six of nine patients tested (four HL, two PMBCL), and three of these HL patients showed PR (n = 2) or SD (n = 1). None of the three HL patients shown to not have JAK2 amplification responded to ruxolitinib. Most treatment-related adverse events were grade 1 or 2 and manageable. Conclusions Ruxolitinib has single-agent activity against HL but does not act against PMBCL with or without JAK2 amplification.

Front line therapy with gemcitabine(G) administered immediately prior to pemetrexed (P) for patients (pts) with advanced or metastatic non-small cell lung cancer (NSCLC): Final report of a phase II clinical trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7116-7116
Author(s):  
H. J. West ◽  
R. J. Belt ◽  
H. A. Wakelee ◽  
M. J. Monberg ◽  
L. A. Frye ◽  
...  
Keyword(s):  
Phase Ii ◽  
Single Agent ◽  
Locally Advanced ◽  
Stage Iv ◽  
Dose Intensity ◽  
Therapeutic Index ◽  
Large Cell ◽  
Stage Iiib ◽  
Final Report ◽  
Front Line

7116 Background: P and G have well demonstrated, single-agent activity in pts with locally advanced or metastatic NSCLC. This phase II study was designed to determine the activity of the combination of PG when G was administered immediately prior to P on day 8 of a 21-day cycle. Methods: Pts with Stage IIIB/IV NSCLC were enrolled. Treatment was G 1250 mg/m2 on D 1 and 8, with P 500 mg/m2 on D 8, immediately following G. Treatment was repeated every 21 days for 6 cycles. Pts received folic acid, vitamin B12 and steroid prophylaxis. Results: 54 pts (32 M/22 F) were enrolled in the study. Median age was 65.0 (range = 43 - 87) years, ECOG PS 0: 1 = 35.2%: 57.4%; Stage IIIB (9.3%), Stage IV (90.7%); Histology: adeno (61.1%) squamous (18.5%), and large cell (5.6%). Median dose intensity was 83.2% for P and 82.2% for G. Grade 3 toxicities were neutropenia (12.0%), thrombocytopenia (8.0%), dyspnea (16.0%), febrile neutropenia (10.0%), anemia (4.0%), fatigue (18.0%), nausea (10.0%), vomiting (8.0%), and rash (2.0%). Grade 4 toxicities were neutropenia (28%), thrombocytopenia (4%), dyspnea (6%), anemia (0%), fatigue (4%), nausea (0%), vomiting (0%), rash (0%). Five patients (10%) experienced Grade 1 alopecia. Median TTPD was 4.4 months and survival was 10.6 months. There were 0 CR, 16 PR (35.6%), 16 SD (35.6%), and 12 PD (26.7%), for an overall best response rate of 35.6%. Conclusions: In this study, PG had a disease control rate (ORR + SD) of 71.1% in the front-line treatment of NSCLC, suggesting that this is an active doublet. Administering P on D 8 rather than D 1 did not seem to negatively impact the therapeutic index. [Table: see text]

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