Phase II Trials of Clofarabine in Relapsed or Refractory Pediatric Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 684-684 ◽  
Author(s):  
Sima Jeha ◽  
Bassem I. Razzouk ◽  
Michael E. Rytting ◽  
Paul S. Gaynon ◽  
Richard Kadota ◽  
...  
Keyword(s):  
Median Survival ◽  
Phase Ii ◽  
Median Duration ◽  
Single Agent ◽  
Median Number ◽  
Phase Ii Trials ◽  
Open Label ◽  
Two Phase ◽  
Pediatric Leukemia ◽  
Phase Ii Studies

Abstract Background: Clofarabine, a next generation nucleoside analogue, was well tolerated and demonstrated activity in adult and pediatric Phase I trials conducted in heavily pretreated leukemia patients. Multicenter Phase II studies in pediatric leukemia have completed accrual in the US and are reported here. Methods: Two Phase 2, multicenter, open-label studies were conducted with clofarabine in children with refractory or relapsed ALL or AML. Clofarabine was administered intravenously over 2 hours at 52 mg/m2/day for 5 consecutive days. Cycles were repeated every 2 to 6 weeks based on response and toxicity. Results: The studies enrolled 100 patients (60 ALL and 40 AML). Currently, data are available for 84 patients (49 ALL, 35 AML). Median age is 12 years (range 1 to 22 years) and median number of prior regimens is 3 (range 1 to 6). Thirty-nine percent had received prior bone marrow transplant (BMT). As determined by independent review, preliminary data indicate overall response rates of 31% in ALL (6 CR, 4 CRp, and 5 PR) and 26% in AML (1 CRp and 8 PR). Median duration of remission for ALL is 9.7 weeks (range 1.0 to 28.6) and for AML is 16.2 weeks (range 1.7 to 56.6+). Thirteen of 24 responding patients (54%) proceeded to BMT. Median survival was 42 weeks (range 7.0 to 63.1+) for responding ALL patients (CR+CRp+PR) and 39 weeks (range 7.7 to 93.6+) for responding AML patients (CRp+PR). Patients who failed treatment or were non-evaluable had shorter median survival; 7.4 weeks (range 0.9 to 40.1+) and 12.4 weeks (range 1.6 to 84.9+) for ALL and AML, respectively. Among the patients who were refractory to the last prior chemotherapy, 7/30 (23%) with ALL and 4/22 (18%) with AML achieved a response with clofarabine. Median duration of remission in these patients is 4.6 weeks (range 2.3 to 24.4+) for ALL and 20 weeks (range 1.7 to 56.6+) for AML. Most drug-related adverse events were transient including febrile neutropenia, diarrhea, nausea/vomiting, fever, skin rash, headache, elevation in liver enzymes and bilirubin, and infusion-related flushing and anxiety. Conclusions: Clofarabine is active as a single agent in pediatric ALL and AML that are refractory to intensive salvage regimens. The overall safety profile is similar to that reported in other pediatric salvage studies. Clofarabine in combination with standard chemotherapy is currently under investigation in children.

Impact of gender on multikinase inhibitors (MKIs) toxicity in patients (pts) with advanced pancreatic and gastrointestinal neuroendocrine tumors (NETs): A pooled analysis of two phase II trials with pazopanib and lenvatinib.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4109-4109
Author(s):  
Jorge Hernando-Cubero ◽  
Enrique Grande ◽  
Daniel E. Castellano ◽  
Toni Ibrahim ◽  
Nicola Fazio ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Phase Ii ◽  
Liver Toxicity ◽  
Task Force ◽  
Pooled Analysis ◽  
Phase Ii Trials ◽  
Open Label ◽  
Two Phase ◽  
Phase Ii Studies ◽  
Grade 3

4109 Background: Retrospective data in some cancer types suggested a possible different toxicity profile with chemotherapy and targeted therapies according to gender. However, data from prospective studies are still very limited, especially in infrequent tumors such as NETs. Methods: Pts with advanced pancreatic and gastrointestinal NETs treated with pazopanib or lenvatinib in the multicenter open-label phase II studies PAZONET and TALENT respectively, were included in the analysis. Both studies were performed by Spanish Task Force Group for Neuroendocrine Tumors (GETNE). All toxicity grades with an incidence higher than 5% were considered for univariate review. Additionally, all grade 3-4 toxicities were analyzed separately. Results: 155 pts (47.7% female) with 1213 adverse events (AEs) (20% G3-4) divided in 121 categories were included. In female patients, liver toxicity, headache, pyrexia, nausea/vomiting, hair/skin disorders and dizziness were significantly more common (table). The only toxicity with higher incidence in men was dysphonia (OR 0.42, 95% CI 0.2-0.9, p 0.02). There were no gender differences in grade 3-4 toxicities. Conclusions: We observed significant differences in toxicity AEs by gender in two prospective phase II studies with MKIs in NETs patients. Potential different approach to manage toxicity may be adopted based on gender. [Table: see text]

Phase II trial of panobinostat (LBH589) in patients (pts) with refractory metastatic colorectal cancer (MCRC).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 582-582 ◽  
Author(s):  
Philip Jordan Gold ◽  
David A. Smith ◽  
Desiree Iriarte ◽  
Barry Boatman ◽  
Henry G. Kaplan
Keyword(s):  
Median Survival ◽  
Phase Ii ◽  
Performance Status ◽  
Single Agent ◽  
Median Number ◽  
Open Label ◽  
Ecog Performance Status ◽  
Treatment Regimes ◽  
Open Label Phase ◽  
Secondary Endpoints

582 Background: LBH589 is a novel histone deacetylase inhibitor (HDACi) which induces apoptosis of tumor cells. LBH589 has been shown to cause regression of colon cancer in animal models and phase I trials have shown the agent to be well tolerated, providing rationale for studying this agent in pts with MCRC. Methods: This was a multicenter, open-label phase II study of single agent LBH589 in patients with MCRC who failed at least 2 prior regimens for metastatic disease. Measurable disease, adequate organ function and ECOG performance status of 0-2 were required. Pts received LBH589 30mg po on M/W/F until disease progression. Pts were evaluated for toxicity every 2 weeks and for response every 8 weeks. The primary endpoint was overall survival. Secondary endpoints included response rate, time to progression (TTP), and toxicity. Results: 29 pts were enrolled (16 male, 13 female). The median age was 59 (range 41-76). The median number of prior treatment regimes was 3 (2-11). The median survival was 5.1 months (range 1-24+). There were no objective responses. 3 pts had SD at 8 weeks. The median TTP was 7.7 weeks (range 1-38.). Six pts had grade 4 thrombocytopenia requiring platelet transfusion. Nine pts required dose reductions for toxicity. Conclusions: Single-agent LBH589 was not associated with objective tumor responses in this heavily pre-treated pt population. However, the median survival was comparable to that seen in other trials of single agent targeted therapy in the treatment of refractory MCRC. Thrombocytopenia was significant, and may complicate potential trials of combination therapy.

scholarly journals Phase II Study of Temsirolimus in Women With Recurrent or Metastatic Endometrial Cancer: A Trial of the NCIC Clinical Trials Group

2011 ◽  
Vol 29 (24) ◽  
pp. 3278-3285 ◽  
Author(s):  
Amit M. Oza ◽  
Laurie Elit ◽  
Ming-Sound Tsao ◽  
Suzanne Kamel-Reid ◽  
Jim Biagi ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Partial Response ◽  
Phase Ii ◽  
Median Duration ◽  
Stable Disease ◽  
Mutational Analysis ◽  
Single Agent ◽  
Protein Translation ◽  
Mtor Inhibition ◽  
Phase Ii Studies

Purpose Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene, and loss of function mutations are common and appear to be important in the pathogenesis of endometrial carcinomas. Loss of PTEN causes deregulated phosphatidylinositol-3 kinase/serine-threonine kinase/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling which may provide neoplastic cells with a selective survival advantage by enhancing angiogenesis, protein translation, and cell cycle progression. Temsirolimus, an ester derivative of rapamycin that inhibits mTOR, was evaluated in this setting. Patients and Methods Sequential phase II studies evaluated single-agent activity of temsirolimus in women with recurrent or metastatic chemotherapy-naive or chemotherapy-treated endometrial cancer. Temsirolimus 25 mg intravenously was administered weekly in 4-week cycles. Results In the chemotherapy-naive group, 33 patients received a median of four cycles (range, one to 23 cycles). Of the 29 patients evaluable for response, four (14%) had an independently confirmed partial response and 20 (69%) had stable disease as best response, with a median duration of 5.1 months (range, 3.7 to 18.4 months) and 9.7 months (range, 2.1 to 14.6 months). Only five patients (18%) had progressive disease. In the chemotherapy-treated group, 27 patients received a median of three cycles (range, one to six cycles). Of the 25 patients evaluable for response, one (4%) had an independently confirmed partial response, and 12 patients (48%) had stable disease, with a median duration of 4.3 months (range, 3.6 to 4.9 months) and 3.7 months (range, 2.4 to 23.2 months). PTEN loss (immunohistochemistry and mutational analysis) and molecular markers of PI3K/Akt/mTOR pathway did not correlate with the clinical outcome. Conclusion mTOR inhibition with temsirolimus has encouraging single-agent activity in endometrial cancer which is higher in chemotherapy-naive patients than in chemotherapy-treated patients and is independent of PTEN status. The difference in activity according to prior therapy should be factored into future clinical trial designs.

Phase II trial of sorafenib (bay 43–9006) in patients with advanced anaplastic carcinoma of the thyroid (ATC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6058-6058 ◽  
Author(s):  
G. Nagaiah ◽  
P. Fu ◽  
J. K. Wasman ◽  
M. M. Cooney ◽  
C. Mooney ◽  
...  
Keyword(s):  
Median Time ◽  
Phase Ii ◽  
Median Duration ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Median Number ◽  
Anaplastic Carcinoma ◽  
Open Label ◽  
Open Label Phase ◽  
Number Of Cycles

6058 Background: Sorafenib (bay 43–9006) is an oral, small molecule tyrosine kinase inhibitor of the raf-1 protein kinase receptor, VEGFR2 and PDGFR-β with antiangiogenic properties. We are conducting an open label, phase II study of sorafenib in patients with biopsy-proven ATC to evaluate if its objective response rate is >20% and to further characterize its safety profile. Methods: Patients with progressive ATC, after cytotoxic chemotherapy with or without radiation were given sorafenib, on a fixed dosing schedule of 400 mg PO bid on 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or patient refusal. Response was evaluated every 8 weeks with body scans using RECIST criteria. We employed a 2-stage study design: if none of the first 18 patients respond the study is terminated, otherwise accrual is continued to a total of 36 patients at which point if ≤3 of the patients respond, the treatment option is rejected. Results: To date 16 patients (10 male) have enrolled in the study. Median age is 55 years; with (range 28–79). Median time on study is 2 months. Median number of cycles given is 2 (range 1–27). Two of 15 evaluable patients (13%) have partial response (PR) and 4 patients (27%) have stable disease (SD). Median duration of PR/SD is 5.1 months (range 1–24.7months). Median time to progression is 1.5 months. Median duration of survival is 3.5 months (range 1–26 months). All patients at time of reporting are deceased. Most common toxicities are lymphopenia (81%) and fatigue (62%). Grade 3 toxicities include lymphopenia (25%), rash with desquamation, weight loss, and chest pain (all 12%). Grade 4 toxicities include dyspnea (6%) and lymphopenia (6%). There has been no significant cardiovascular toxicity. One patient died on study with rapidly progressive disease. Conclusions: Sorafenib demonstrates objective tumor response in the first 15 evaluable and pretreated patients with advanced ATC. This trial is ongoing and supported in part by NIH grant nos. CA62502. [Table: see text]

Nonpegylated liposome-encapsulated doxorubicin (NPLED) and cyclophosphamide in the treatment of platinum-resistant ovarian cancer: Final results of a phase II study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15544-e15544
Author(s):  
Daniela Sambataro ◽  
Melania Caruso ◽  
Concetta Di Blasi ◽  
Giuseppe Lavenia ◽  
Salvatore Asero ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Single Agent ◽  
Progression Free Survival ◽  
Median Number ◽  
Open Label ◽  
Open Label Study ◽  
Free Survival ◽  
Resistant Refractory ◽  
Platinum Resistant

e15544 Background: Platinum resistant-refractory ovarian cancer (PRROC) patients have a poor outcome; single-agent therapy is still the gold standard, with overall response rate lesser than 20% and progression-free-survival is not higher than 4 months. Methods: We tested safety and activity of a two-drugs-regimen containing NPLED and cyclophosphamide in a phase II open label study. From October 2007 to October 2011 thirty-two patients with platinum-resistant/refractory disease were enrolled. Enrolled patients were pretreated with a median number of 2 lines of chemotherapy, ranging from 1 to 5. NPLED and cyclophosphamide were administered at the dose of 60 mg. and 600 mg p.s.m. respectively. Results: Patients received a median number of three cycles of chemotherapy. A total of 145 cycles were administered: as G3 toxicities we registered emesis (6%), diaorrhea (3%), asthenia, and alopecia. No grade 4 adverse events occurred. Among the 30 patients evaluable for response we observed 5 (17%) partial responses and 10 (33%) stable diseases. The median progression-free-survival was 13 weeks and the median survival was 46 weeks. Conclusions: These results are similar to other data reported in literature. In conclusion we may affirm that the association of NPLED and cyclophosphamide is active and safe when administered in PRROC, but it don’t modify the prognosis of this subset of patients.

Phase II Study of Clofarabine in Pediatric Patients With Refractory or Relapsed Acute Lymphoblastic Leukemia

2006 ◽  
Vol 24 (12) ◽  
pp. 1917-1923 ◽  
Author(s):  
Sima Jeha ◽  
Paul S. Gaynon ◽  
Bassem I. Razzouk ◽  
Janet Franklin ◽  
Richard Kadota ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Phase Ii ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Single Agent ◽  
Median Number ◽  
Open Label ◽  
Hematopoietic Stem ◽  
Platelet Recovery ◽  
Heavily Pretreated

Purpose To evaluate the efficacy and safety of clofarabine, a novel deoxyadenosine analog, in pediatric patients with refractory or relapsed acute lymphoblastic leukemia (ALL). Patients and Methods In a phase II, open-label, multicenter study, 61 pediatric patients with refractory or relapsed ALL received clofarabine 52 mg/m2 intravenously over 2 hours daily for 5 days, every 2 to 6 weeks. The median age was 12 years (range, 1 to 20 years), and the median number of prior regimens was three (range, two to six regimens). Results The response rate was 30%, consisting of seven complete remissions (CR), five CRs without platelet recovery (CRp), and six partial remissions. Remissions were durable enough to allow patients to proceed to hematopoietic stem-cell transplantation (HSCT) after clofarabine. Median CR duration in patients who did not receive HSCT was 6 weeks, with four patients maintaining CR or CRp for 8 weeks or more (8+, 12, 37+, and 48 weeks) on clofarabine therapy alone. The most common adverse events of grade ≥ 3 were febrile neutropenia, anorexia, hypotension, and nausea. Conclusion Clofarabine is active as a single agent in pediatric patients with multiple relapsed or refractory ALL. The toxicity profile is as expected in this heavily pretreated patient population. Studies exploring rational combinations of clofarabine with other agents are ongoing in an effort to maximize clinical benefit.

Trabectedin (T) in relapsed advanced ovarian cancer (ROC): A pooled analysis of three phase II studies

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5579-5579 ◽  
Author(s):  
S. McMeekin ◽  
J. M. del Campo ◽  
N. Colombo ◽  
C. Krasner ◽  
A. Roszak ◽  
...  
Keyword(s):  
Phase Ii ◽  
Single Agent ◽  
Advanced Ovarian Cancer ◽  
Dose Intensity ◽  
Pooled Analysis ◽  
Phase Iii ◽  
Clinical Activity ◽  
Weekly Schedule ◽  
Phase Ii Trials ◽  
Phase Ii Studies

5579 Introduction: Trabectedin is a DNA minor groove binding drug with a distinct MoA under development in sarcoma, prostate, breast and ROC. We have performed a pooled analysis of efficacy and tolerability of all phase II trials with T as 2nd - 3rd line in ROC. Methods: Three Trabectedin schedules were investigated: two every 3weeks (q3w; A: 1.3 mg/m2 3-h or B: 1.5 mg/m2 24-h) and one weekly (C: 0.58 mg/m2 3-h ×3 q4w). Endpoints were response rate (RR), time to progression (TTP), response duration (RD) and safety. 294 patients from 3 phase II (one randomized A vs B) trials were included: 108 were resistant (R) and 186 sensitive (S) to last platinum, based on progression-free interval <6 months or longer.Results: Overall RR and median TTP were 8% and 2.1mo in R and 34% and 5.8 mo in S patients. Median RD was 5.8 m. Schedules A & B q3w showed significant better RR (33% vs 16%, p=<0.0001) and median TTP (5.8 vs 2.8 m, p=0.0001) than the weekly schedule C. No efficacy difference was seen between 3-h and 24-h q3wk. In patients with = 2 prior platinum-based regimens, RR (R:7% and S:37%) and median TTP (R: 2.5 m and S:6.3 m) were similar than patients with only 1 prior platinum [RR (R:9%; S:33%) and TTP (R: 2 m; S: 5.5 m)]. 1,404 cycles were delivered [median A: 5(1–23), B: 5(1–19), C: 3(1–22)], with similar dose intensity (mg/m2/wk) across regimens (0.38, 0.42, 0.39). Most common drug-related AEs of any grade by cycle were (A, B, C) fatigue: 38, 35, 63% and vomiting: 16, 27, 21%. Grade 3/4 lab abnormalities were non-cumulative neutropenia: 21, 28, 1% and ALT increase: 32, 26, 3%. Low incidence of febrile neutropenia, neurotoxicity, stomatitis and alopecia was seen regardless of schedule. Conclusions: Trabectedin as single agent has shown clinical activity in both R and, particularly in S ROC. Activity was fully retained in patients with =2 prior platinum lines. Trabectedin q3w schedules (with no difference between 3 and 24-h) showed higher efficacy than T weekly. Toxicities were manageable and non-cumulative. Trabectedin is a promising new drug for the treatment of ROC and is under evaluation in a phase III trial. No significant financial relationships to disclose.

Biomodulation of capecitabine by weekly paclitaxel and carboplatin in patients with advanced solid tumor malignancies: A dose-escalating phase I study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2569-2569
Author(s):  
M. B. Lustberg ◽  
J. Nuovo ◽  
J. P. Thomas ◽  
P. J. Monk ◽  
S. Kim ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Phase I Study ◽  
Dihydropyrimidine Dehydrogenase ◽  
Weekly Paclitaxel ◽  
Unknown Primary ◽  
Cancer Tissue ◽  
Phase Ii Trials ◽  
Two Phase ◽  
Phase Ii Studies

2569 Background: A principal determinant of the therapeutic index with capecitabine-based treatment is the grade of thymidine phosphorylase (TP) activity in malignant tissue. The beneficial interactions of paclitaxel and carboplatin in upregulation of TP promise to make capecitabine more tumor specific and to provide the expected synergy. On the basis of the time-dependency and transiency for this upregulation we performed a phase I study of capecitabine in combination with weekly paclitaxel and carboplatin (CTX). Methods: Patients with advanced solid tumors received carboplatin on day 1, paclitaxel on days 1, 8, 15 and capecitabine orally twice a day on days 8–21, every 4 weeks. There were 5 planned dose levels (DL 1–5). Paclitaxel was escalated from 60 mg/m2 to 80 mg/m2 (DL 4) then 100 mg/m2 (DL 5). Capecitabine from 500 mg/m2 bid to 750 mg/2 bid (DL 2) then 1000 mg/m2 bid (DL 3–5). Carboplatin dose was fixed at AUC 6. Paraffin-embedded tissue was evaluated for expression of TP, thymidylate synthase and dihydropyrimidine dehydrogenase by immunohistochemistry. Results: 32 patients from Ohio State University (OSU) were enrolled. 84% had prior therapy. The most common grade 3/4 toxicities were neutropenia (59%), leukopenia (56%), and fatigue (16%). DLTs included neutropenic fever (1), prolonged neutropenia or thrombocytopenia (2) and diarrhea (1). The MTD was at DL 2. There were 10 confirmed responses [4 CR (esophagus, stomach, unknown primary and ampullary); 6 PRs (Pancreas (3), unknown primary, anal and esophagus] and stabilization of disease > 3 months in 12 patients. In normal tissue, there was no difference in expression levels of both TS and TP. On the other hand, in cancer tissue, TP levels seem to correlate with response whereas TS did not. Conclusions: CTX demonstrates acceptable tolerability. The recommended doses for phase II studies are capecitabine 750 mg/m2 bid, paclitaxel 60 mg/m2/week and carboplatin AUC=6. The acceptable toxicity profile in this dose schedule, and the promising antitumor activity observed warrant further evaluation of this regimen. Two phase II trials are already underway at OSU using this regimen for patients with pancreatic cancer and adenocarcinomas of unknown primary, the latter already actively enrolling patients. Pretreatment tumoral TP levels may help predict patients that are more likely to respond to CTX. Correlation of IHC data with responses will be presented at the meeting. [Table: see text]

The Efficacy and Safety of Lenalidomide Oral Monotherapy in Patients with Mantle Cell Lymphoma Previously Treated with Bortezomib: Pooled Data from Two Phase II Studies (NHL-002 and NHL-003).

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1560-1560 ◽  
Author(s):  
Craig B. Reeder ◽  
T.E. Witzig ◽  
Julie M. Vose ◽  
Pier Luigi Zinzani ◽  
Rena Buckstein ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Phase Ii ◽  
Cell Lymphoma ◽  
Single Agent ◽  
B Cell Lymphoma ◽  
Prior Treatment ◽  
Cell Transplant ◽  
Phase Ii Trials ◽  
Phase Ii Studies ◽  
Mantle Cell

Abstract Introduction: Mantle-cell lymphoma (MCL) is an aggressive B-cell lymphoma that if not cured with aggressive chemoimmunotherapy and stem cell transplant is usually fatal. The intravenous proteasome inhibitor bortezomib produces an overall response rate (ORR) of 33% in patients with relapsed MCL (J Clin Oncol2006;24(30):4867–74). Unfortunately, most patients eventually relapse and new agents are needed for this disease. Two recently conducted phase II trials (NHL-002 and NHL-003) tested single-agent lenalidomide for patients with relapsed MCL. Fifty-four patients with MCL were enrolled into the two studies; 26% (14/54) had received prior bortezomib and they are the subject of this report. Methods: Patients with relapsed or refractory MCL and measurable disease 2 cm after at least one prior treatment regimen including prior bortezomib were eligible. Patients received 25 mg of lenalidomide orally once daily on days 1–21 of every 28-day cycle. Therapy was continued as tolerated or until disease progression. The 1999 IWLRC methodology was used to assess response and progression. Results: The 14 patients in this study were heavily pretreated with a median of 4 (2–6) prior treatments (including bortezomib) and 50% were bortezomib-refractory. Median age was 66 (45–84) years and 6 (43%) patients were female. Median time from diagnosis to lenalidomide treatment was 3.3 (0.7–7.6) years. The ORR with lenalidomide was 57% (8/14), including 21% (3/14) complete response (CR)/unconfirmed CR and 36% (5/14) partial responses. One (7%) patient had stable disease. The most common grade 3 or 4 adverse events were neutropenia (50%), thrombocytopenia (43%), anemia (21%), fatigue (21%), and leukopenia (21%). Neutropenic fever occurred in 7% of patients. Conclusion: These results demonstrate that lenalidomide oral monotherapy is very effective with manageable side effects in patients with relapsed or refractory MCL who had received prior treatment with bortezomib.

Safety summary of panitumumab (pmab) in combination with chemotherapy (ctx) from four clinical trials in patients (pts) with metastatic colorectal cancer (mCRC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15005-e15005
Author(s):  
T. J. Price ◽  
M. Peeters ◽  
J. Douillard ◽  
E. Mitchell ◽  
A. Cohn ◽  
...  
Keyword(s):  
Phase Ii ◽  
Safety Data ◽  
Data Monitoring Committee ◽  
Phase Iii ◽  
Phase Ii Trials ◽  
Two Phase ◽  
Phase Ii Studies ◽  
Study Results ◽  
Phase Iii Trials ◽  
Phase Iii Studies

e15005 Background: Pmab is a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody approved in the US and EU (wild-type KRAS) as monotherapy for pts with mCRC. Safety data from 4 studies (Siena et al ASCO 2008; Peeters et al ASCO 2008; Cohn et al ASCO 2008; Mitchell et al WORLD GI 2008) of pmab in combination with ctx are summarized. Methods: Two studies are single-arm, phase II trials and two are randomized, phase III trials with pooled, blinded safety data that include ctx-controls. All studies were multicenter. Common pt eligibility criteria included: diagnosis of mCRC with measurable disease per modified RECIST criteria, age ≥ 18 years, and adequate hematologic, renal, hepatic, and metabolic function. All studies required pts to receive FOLFOX, FOLFIRI, or irinotecan ctx in combination with pmab. Pts received pmab 6.0 mg/kg Q2W with FOLFOX Q2W or FOLFIRI Q2W, or pmab 9.0 mg/kg Q3W with irinotecan Q3W. Results from planned interim analyses are available for 3 studies, and results from the final analysis are available for one study. Results: Among the 4-study safety data, 1213 pts received pmab + ctx; 703 pts received pmab + FOLFIRI, 455 pts received pmab + FOLFOX, and 55 pts received pmab + irinotecan. Approximately 1,200 pts were enrolled in each phase III study, and data are available from 1,003 pts who received pmab + ctx and 997 pts who received ctx alone. All pts in the phase III studies, regardless of treatment group, were included in the pooled, blinded interim analysis sets monitored by the data monitoring committee for each study. Safety results for the two phase II studies of pmab + ctx and two phase III studies of pmab ± ctx are summarized (Table). Conclusions: Phase II data are consistent with expectations, and phase III trials are ongoing. A consistent safety profile was observed across studies. [Table: see text] [Table: see text]

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