An update on gemcitabine, rituximab, and oxaliplatin in combination for relapsed/refractory non-Hodgkin lymphomas.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8084-8084
Author(s):  
Robert M. Crescentini ◽  
Kendra Lynn Sweet ◽  
Jijun Liu ◽  
Idalia Liboy ◽  
Samir Dalia ◽  
...  
Keyword(s):  
B Cell ◽  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Cell Transplant ◽  
Ecog Performance Status ◽  
Salvage Regimen ◽  
Bulky Disease ◽  
Grade 3 ◽  
Large B Cell

8084 Background: Relapsed/refractory non-Hodgkin lymphomas (NHL) have no standard of care. A variety of salvage chemotherapy options are available. We previously reported results of our phase II trial using gemcitabine, rituximab and oxaliplatin (GROC) in the salvage setting for relapsed/refractory NHL in which we observed an overall response rate of 58% with an incidence of grade 3-4 thrombocytopenia of 9% and neutropenic fever of 3.5%, but no grade 3-4 non-hematologic toxicities. Here we update progression free survival (PFS) and overall survival (OS) data. Methods: This phase II, single-arm, multicenter study evaluated safety and efficacy of GROC in patients with relapsed/refractory NHL. Patients were treated on a 14 day cycle. On day 1, patients with CD20+ NHL received rituximab (375 mg/m2). On day 2, patients received gemcitabine (1000 mg/m2) and oxaliplatin (100 mg/m2). Granulocyte colony stimulating factor was given. Stem cell transplant (SCT) was considered after a minimum of 6 cycles. Results: A total of 58 patients were enrolled from the H. Lee Moffitt and the Auxilio Mutuo Cancer Centers. Ages ranged from 24 to 88 years (median 72 years). The majority of patients had an ECOG performance status of 0-1 (89%). Lymphoid neoplasms included large B-cell (79%), follicular (7%), lymphoblastic (1.8%), Burkitt (1.8%), primary mediastinal large B-cell (3.5%), and peripheral T-cell lymphoma (7%). Eighty-one percent of patients had stage III-IV disease, median IPI was 3, 40% had B-symptoms, 43% had bulky disease and 74% had an elevated LDH. Anthracycline-based therapy had been used in 91% of patients and 66% had received rituximab. Median PFS was 134 days (95% CI 115-153) and median OS was 296 days (95% CI 164-428). No difference in response was observed based on age >60, IPI, LDH or albumin levels. Prior therapy with rituximab (p=0.02) and initial response to front-line therapy (p=0.04) appear to correlate with improved outcomes. Nine patients went on for SCT. Conclusions: GROC is a useful salvage regimen for relapsed/refractory NHL with minimal toxicities and good clinical efficacy. Several patients were able to be successfully mobilized, collected and transplanted post GROC therapy.

Treatment of Diffuse Large B-Cell Lymphoma with Rituximab, Intensive Induction and High-Dose Consolidation: The Final Analysis of the Czech Lymphoma Study Group (CLSG) R-MegaCHOP-ESHAP-BEAM (R-MEB) Trial.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 21-21
Author(s):  
Marek Trneny ◽  
Robert Pytlik ◽  
David Belada ◽  
Katerina Kubackova ◽  
Ingrid Vasova ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Performance Status ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background. Combined immunochemotherapy with CHOP and rituximab have improved the outcome of patients with diffuse large B-cell lymphoma (DLBCL). and related diseases. However, the cure rate of patients with IPI 3–5 or aaIPI 3 is still only about 50% with this regimen. Given the feasibility of previous CLSG regimens based on high-dose CHOP-ESHAP induction and BEAM consolidation, we have conducted a phase II trial combining this approach with rituximab immunotherapy. Patients and methods. Patients aged 18–65 years with DLBCL and age-adjusted IPI (aaIPI) 2–3 were treated with three cycles of high-dose CHOP (MegaCHOP - cyclophosphamide, 3 g/m2, vincristine 2 mg, adriamycin, 75 mg/m2, and prednisone, 300 mg/m2) with G-CSF every 3 weeks, followed by three cycles of ESHAP (etoposide, 240 mg/m2, cisplatin, 100 mg/m2, methylprednisolone, 2000 mg and Ara-C 2000 mg/m2) every 3 weeks. Four to six doses of rituximab 375 mg/m2 were administered on day 1 of each cycle of induction therapy. High-dose therapy (BEAM) followed by autologous stem cell transplant (ASCT) was used as consolidation. Radiotherapy was given to residual masses or sites of bulky disease. Primary endpoint was progression-free survival (PFS), while secondary endpoints were overall survival (OS) and feasibility of the treatment. Results. From April 2002 to October 2006, 105 consecutive patients from 10 centers were recruited. 58% were men and 42% women with median age 46 years (19–63 years). 74% of patients had stage IV disease, 92% had elevated LDH, 53% had performance status >1, 55% had B symptoms and 19% had bone marrow involvement. aaIPI was 2 in 62% of patients and 3 in 38% of patients. 68% of patients received the whole treatment according to the protocol, including ASCT and radiotherapy. Stem cells mobilization according to the protocol was performed in 90% of patients and was successful in 86% of mobilized patients (77% of all patients). 73% of patients ultimately received ASCT (including 3 patients transplanted after ammended treatment) and 51% of patients received planned radiotherapy. Complete remission (CR) was achieved in 83% of all patients and partial remission (PR) in 2%. Early toxic death rate was 6% and 9% patients had primary refractory disease. Of patients who achieved CR or PR, only 6 subsequently relapsed (7%) and two suffered late toxic death (2%). With a median follow-up of 32 months for living patients, the estimated 2-year PFS is 77% and 2-year OS is 81%. Age less than median (46 years) was strongest predictor of favorable outcome (p = 0,00006 for PFS and p = 0,00013 for OS), while there was no effect of stage, LDH, performance status or aaIPI (2-year PFS 79% for aaIPI 2 and 77% for aaIPI 3, 2-year OS 81% for aaIPI 2 and 80% for aaIPI 3). Delivery of ASCT or radiotherapy did not significantly affected PFS in patients who did not suffered early progression or early toxic death, but radiotherapy modestly improved OS of these patients (p = 0,03). Conclusion. R-MEB has proved to be an effective treatment strategy for younger patients with high-risk aggressive B-cell lymphoma. Currently, CLSG is testing whether utilization of early PET scan may decrease toxicity and improve treatment tolerance while maintaining the efficacy of this regimen.

Phase II study of pazopanib with weekly paclitaxel in refractory urothelial cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 294-294 ◽  
Author(s):  
Sandy Srinivas ◽  
Sujata Narayanan ◽  
Lauren Christine Harshman ◽  
Russell Kent Pachynski ◽  
Anthony P. Lam ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Progression Free Survival ◽  
Median Number ◽  
Upper Urinary Tract ◽  
Weekly Paclitaxel ◽  
Moderate Activity ◽  
Ecog Performance Status ◽  
Grade 3

294 Background: Currently, there are no standard treatments for relapsed or refractory urothelial carcinoma (UC). Discouraging results have been observed in trials evaluating established chemotherapeutics as single agents or in combination regimens. Paclitaxel has moderate activity when used alone and in combination in UC. Pazopanib is active in other solid tumors secondary to its potent anti-angiogenic effects. We report the results of a multi-center phase II study evaluating the combination of paclitaxel with pazopanib in refractory UC. Methods: Eligible patients (pts) had histologically confirmed UC, with disease that progressed on upto 2 chemotherapeutic regimens. Pazopanib (800 mg) was administered daily, with weekly paclitaxel (80mg/m2) for 3 weeks in a 28 day cycle. Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint of the study was response-rate (RR) based on RECISTv 1.1 criteria. Secondary endpoints included safety, and progression free-survival (PFS). Results: From April 2010 to September 2014, 32 patients were enrolled. Median age was 67 years (29-89) and median ECOG performance status was 1 (0-2). 17 pts (54%) had UC of the upper urinary tract disease and 15(47%) had primary bladder tumors. All pts had multiple metastatic sites, including 9 (28%) with liver metastases. Median number of prior cytotoxic regimens was 2, and 50% were considered cisplatin responsive. Objective responses were observed in 58% with 3 (12%) complete responses (CR), and 12 pts (46%) with partial responses (PR). Another 9 (35%) acheived stable disease (SD). High grade toxicities included grade 3 hypertension (n=2), grade 3 fatigue (n=4), grade 3 thrombosis (n=2) and grade 4 neutropenia (n=2). Nearly half of the patients( n= 14 ) required growth factor support. Conclusions: Our phase II study combining paclitaxel and pazopanib demonstratedsignificant anti-tumor activity in relapsed/refractory UC. This combination is safe, effective and is worthy of evaluation in randomized phase 3 study. Clinical trial information: NCT01108055.

A Phase II Trial of Darinaparsin in Advanced Lymphomas: Report on Safety and Activity.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1562-1562
Author(s):  
Michael Craig ◽  
Sandip Shah ◽  
Martin Tallman ◽  
Poonam Patil ◽  
Jose Easow ◽  
...  
Keyword(s):  
B Cell ◽  
Phase Ii ◽  
Marginal Zone ◽  
Performance Status ◽  
Autologous Bone Marrow Transplantation ◽  
B Cell Lymphoma ◽  
Low Grade ◽  
Cell Transplant ◽  
Heavily Pretreated ◽  
Large B Cell

Abstract Darinaparsin (ZIO-101) is a novel organic arsenic molecule that has a mechanism of action mediated by targeted disruption of mitochondrial function, modified signal transduction, and antiangiogenesis. It is active against diverse cancers in vitro. This Phase II multi-center trial is being conducted in patients diagnosed with advanced lymphomas that have received at least 1 prior therapy and require additional treatment. Patients receive 300 mg/m2 of darinaparsin intravenously for 5 consecutive days every 28 days (1 cycle) and are then evaluated for efficacy and safety by standard criteria. Treatment continues until toxicity or progression. To date the study has accrued 22 patients (15 non-Hodgkin’s [NHL], 7 Hodgkin’s); 12 are male and 10 are female. Median age at baseline was 60.5 years (range: 28–80), ECOG performance status was ≤2, and median number of prior therapies was 4 (range 2–6). Thirteen subjects have received at least 2 cycles of darinaparsin and are evaluable for efficacy. Of these, 1 (diagnosed with PTCL) has achieved a complete response (CR) and 3 (diagnosed with marginal zone transformed to diffuse large B-cell, marginal zone, and Hodgkin’s nodular sclerosis, respectively) have achieved partial responses (PRs). These patients had been heavily pretreated (PTCL: CHOP, ICE, and EPOCH; marginal zone transformed to diffuse B-cell: RCHOP, RICE, RT and autologous bone marrow transplantation; marginal zone: rituximab, RCVP, and gemcitabine; and Hodgkin’s: ICE, CBV, gemcitabine+ MDX-060, and stem cell transplant). In the patient with transformed diffuse large B-cell lymphoma who achieved PR, no evidence for macroscopic disease was present, but microscopic low-grade marginal zone lymphoma was detectable in random biopsies from normal-appearing gastric mucosa. In addition, 2 patients (diagnosed with PTCL and Hodgkin’s, respectively) have achieved stable disease (SD). The only Grade 3 adverse event (AE) considered drug-related was wheezing. A total of 12 subjects have reported 37 serious adverse events (SAEs) while on study. Of these, only 2 had SAEs that were considered drug-related (neutropenic fever, fall). In conclusion, darinaparsin has been very well tolerated and has demonstrated promising activity in heavily pretreated patients diagnosed with advanced lymphoma. Initial responses (1 CR, 3 PRs, 2 SDs) have been observed among 13 evaluable patients. Accrual continues; additional safety and efficacy data will be reported.

A multicenter phase II study of bendamustine with rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8023-8023 ◽  
Author(s):  
Michinori Ogura ◽  
Kiyoshi Ando ◽  
Nozomi Niitsu ◽  
Seok Jin Kim ◽  
Ken Ohmachi ◽  
...  
Keyword(s):  
B Cell ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Salvage Regimen ◽  
Prior Therapy ◽  
Non Hodgkin Lymphoma ◽  
Grade 3

8023 Background: Effective salvage therapies are needed in patients (pts) with relapsed/refractory DLBCL after R-CHOP. Therapy with bendamustine plus rituximab (B-R) was well tolerated and effective in the preceding phase I study in relapsed/refractory aggressive B-cell non-Hodgkin lymphoma, including DLBCL. This phase II study assessed the efficacy and safety of B-R in pts with relapsed/refractory DLBCL. Methods: Pts with histologically confirmed DLBCL (excluding transformed disease) and 1-3 prior therapies received rituximab 375 mg/m2 IV on day 1 and bendamustine 120 mg/m2 IV on days 2 and 3 of each 21-day cycle, for up to 6 cycles. Recovery of neutrophil count to ≥1,000/mm3 and platelet count to ≥75,000/mm3 were required prior to the start of each cycle; treatment delays >2 weeks resulted in discontinuation. The primary endpoint was overall response rate (ORR); secondary endpoints included complete response (CR) rate, progression-free survival (PFS), and safety. Results: A total of 63 pts were enrolled; data from 59 pts were available. Median age was 67 (range, 36-75) years with 37 pts over 65 years. The majority of pts (64.4%) had 1 prior therapy; 57 pts (96.6%) were previously treated with rituximab-containing combination chemotherapy and 8 (13.6%) had prior auto-PBSCT. Pts received a median of 4 (range, 1-6) treatment cycles. Sixteen (27.1%) pts completed 6 treatment cycles; most common reasons for early discontinuation were disease progression (n=15) and failure to meet criteria to start the next cycle (n=13). Among 59 pts evaluable for response, ORR was 62.7% with a 37.3% CR rate. The median PFS was 200 days (95% CI, 109-410). Most common grade 3/4 adverse events (AEs) included CD4 lymphocytes decreased (66.1%), neutropenia (54.2%), and thrombocytopenia (10.2%). Four (6.8%) pts discontinued due to serious AEs (cytomegalovirus infection, infection, pneumonia, and pneumonia/respiratory failure). Conclusions: B-R demonstrated promising activity in pts with relapsed/refractory DLBCL. Toxicity was primarily hematologic and generally manageable. These results suggest that B-R is a promising salvage regimen for pts with relapsed/refractory DLBCL after R-CHOP.

Phase II study of S-1, oral leucovorin, oxaliplatin, and bevacizumab combination therapy (SOL+BV; SOLA) in patients with unresectable metastatic colorectal cancer (mCRC).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 611-611 ◽  
Author(s):  
Takeshi Kato ◽  
Tomohiro Nishina ◽  
Kentaro Yamazaki ◽  
Takayuki Yoshino ◽  
Yoshinori Miyata ◽  
...  
Keyword(s):  
Phase Ii ◽  
Tumor Regression ◽  
Performance Status ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Prolonged Treatment ◽  
Efficacy And Safety ◽  
Resection Rate ◽  
Ecog Performance Status ◽  
Grade 3

611 Background: The results from a randomized phase II trial in the first-line treatment of mCRC indicated that SOL regimen (S-1, Oral Leucovorin; LV, and Oxaliplatin) had promising activity with well-tolerated toxicities compared to mFOLFOX6 (Ojima et al, ESMO 2011). The median progression-free survival (PFS) for SOL and mFOLFOX6 was 9.6 and 6.9 months, respectively (HR=0.83). We evaluated the efficacy and safety of adding BV to SOL regimen in this study. Methods: The inclusion criteria were; 1) histologically proven adenocarcinoma of colon or rectum, 2) age ≥ 20 years, 3) no prior treatment for metastatic disease, 4) at least one target lesion by RECIST ver1.0 criteria, 5) ECOG Performance Status 0-1. Patients (pts) received S-1 (40-60 mg bid) and LV (25 mg bid) orally for one week and L-OHP (85 mg/m2), and BV (5 mg/kg) on day 1, every 2 weeks. The primary endpoint was the response rate (RR). Results: From October 2009 to April 2010, 31 pts were enrolled, and 29 pts were regarded as the population of full analysis set. Present data included the results of efficacy and safety up to 24 cycles. RR assessed by the independent review committee was 86.2 % (CR: 0 pts, PR: 25 pts), and disease control rate (DCR) was 100%. The median PFS assessed by investigators was 12.5 months, while further follow up is ongoing. One year survival rate was 100%. The incidence of grade 3/4 adverse drug reactions were; neutropenia 16.7%, diarrhea 10.0%, hypertension 16.7%, and sensory neuropathy 53.3%. The median cumulative oxaliplatin dose was 915.0 mg/m2 (range 330-1735 mg/m2). The high prevalence of grade 3 neuropathy seemed due to the prolonged treatment duration. Reasons for discontinuation were progressive disease in 13 pts, and metastatectomy by tumor regression in 6 pts. The resection rate was 17.2 %. Conclusions: SOL+BV showed promising activity with high RR, DCR, PFS and resection rate with well tolerated toxicities in pts with unresectable mCRC. This trial was supported by Taiho Pharmaceutical CO.,LTD. (JAPIC Clinical Trials information Identifier: JapicCTI-090881).

Phase II trial of pazopanib and weekly paclitaxel in metastatic urothelial cancer (UC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 299-299 ◽  
Author(s):  
Sandy Srinivas ◽  
Sujata Narayanan ◽  
Lauren Christine Harshman ◽  
Anthony P. Lam ◽  
Ulka N. Vaishampayan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Urothelial Cancer ◽  
Phase Ii Study ◽  
Performance Status ◽  
Progression Free Survival ◽  
Complete Response ◽  
Weekly Paclitaxel ◽  
Ecog Performance Status ◽  
Metastatic Urothelial Cancer ◽  
Grade 3

299 Background: Currently, there are no standard treatments for relapsed or refractory urothelial carcinoma (UC). Discouraging results have been achieved in trials evaluating drugs as single agents or in combination regimens. Paclitaxel has activity when used alone and in combination in urothelial cancer, and pazopanib is active in solid tumors secondary to its potent anti-angiogenic effect. We report the results of an ongoing multicenter phase II study evaluating the combination of paclitaxel with pazopanib in refractory UC. Methods: Patients (pts) eligible for the study have histologically confirmed UC, with relapse after receiving up to 2 chemotherapeutic regimens. Pazopanib (800 mg) is administered daily, with weekly paclitaxel (80mg/m2) for 3 weeks in a 28 day cycle. Treatment is continued until disease progression or unacceptable toxicity. Primary endpoint of the study is the response-rate (RR) based on RECIST criteria. Secondary endpoints include safety, and progression free-survival (PFS). For designing the study, Simon’s two-stage method was applied, and 9 pts were recruited in the first stage. After having ≥1 response in the first group, a full enrollment of 32 pts has been initiated. Results: 25 pts were enrolled from April 2010 to September 2013. Their median age was 67 years (47-89), with a median ECOG performance status of 1 (0-2). 10 pts (40%) had UC of the upper urinary tract and 15 had primary bladder/ureter tumors. All pts had multiple metastatic sites, including 11 (44%) with liver metastases. Median number of prior cytotoxic regimens was 2, and 50% were considered cisplatin responsive. Based on RECIST (v1.1) criteria,13 pts (52%) had partial response (PR), 5 (20%) had stable disease (SD), and 2 (8%) had complete response (CR) (80% clinical benefit). The side effects included grade 3 hypertension (n=2), grade 3 fatigue (n=4), grade 3 thrombosis (n=2) and grade 4 neutropenia (n=2). 14 pts required growth factor support. Conclusions: Our phase II study combining paclitaxel and pazopanib demonstratedsignificant anti-tumor activity of combining paclitaxel in relapsed/refractory UC. This combination is safe, and is worthy of evaluation in larger studies. Clinical trial information: 1108055.

Phase II study of dasatinib in the treatment of head and neck squamous cell carcinoma (HNSCC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6022-6022 ◽  
Author(s):  
H. D. Brooks ◽  
B. Glisson ◽  
C. Lu ◽  
A. Sabichi ◽  
F. Johnson ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Drug Discontinuation ◽  
Open Label ◽  
Ecog Performance Status ◽  
Open Label Phase ◽  
Grade 3 ◽  
Efficacy Parameters

6022 Background: Dasatinib is a potent inhibitor of src-family kinases, ephA2, PDGFR, Abl, and c-kit. A single-center, open-label, phase II trial was conducted to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of dasatinib in recurrent or metastatic HNSCC. Methods: Pts with measurable disease by RECIST, who received 0 or 1 prior regimen for recurrent or metastatic HNSCC with an ECOG performance status 0–1 and tumor tissue appropriate for IHC and FISH were eligible. Dasatinib 100 mg bid was given for 28-day cycles. Primary endpoints were 12-wk progression-free survival (PFS) and objective response rate (ORR). Pts who took at least 1 dose of dasatinib and who died or left study before 12 wks were counted as progressive disease (PD). A 2 stage design, closure after accrual of 15 pts was required if PFS was 45% or less and ORR was 0. Otherwise, planned accrual was 35. Response was assessed at 4 and 12 wks. PK was studied in pts receiving dasatinib per PEG. Biomarkers relevant to Src pathway were planned in tissue and blood. Results: Fifteen pts were accrued. To date, 13 pts are evaluable for response, and 15 pts for toxicity. No grade 3/4 hematologic toxicities were noted. Grade 2–4 nonhematologic toxicities(n): pleural effusion(2), nausea/vomiting(2), dehydration(1), diarrhea(1), dyspnea(1). Toxicity led to hospitalization of 4 pts and drug discontinuation in 5 pts. ORR was 0. One pt was stable at 12 wks (PFS: 7.6%). This pt stopped drug at 15 wks due to toxicity, but also had PD. One pt died on study and cause was deemed unlikely related. Conclusions: Dosed at 100mg bid, dasatinib led to a characteristic toxicity profile in this pt population. Rates of hospitalization and discontinuation for toxicity were fairly high. Final efficacy parameters are pending evaluation of 2 pts. Evaluation of PK and tissue/blood biomarkers is ongoing. No significant financial relationships to disclose.

A phase II study of capecitabine, irinotecan, and bevacizumab (XELIRI-A) in patients (pts) with previously untreated metastatic colorectal cancer (mCRC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15019-e15019
Author(s):  
E. X. Chen ◽  
S. Welch ◽  
M. Krzyzanowska ◽  
H. MacKay ◽  
J. Knox ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Open Label ◽  
Ecog Performance Status ◽  
Optimal Dosing ◽  
Open Label Phase ◽  
Dosing Strategies ◽  
Grade 3 ◽  
Ecog Ps

e15019 Background: Capecitabine (XEL), irinotecan (IRI) and bevacizumab (A) are all active agents in the treatment of mCRC. However, combining these agents has proven to be problematic due to overlapping toxicities. Optimal dosing strategies for this combination remain unclear. This study prospectively evaluated toxicity and efficacy of the XELIRI-A combination with dose modification. Methods: This was a single-institution, open-label phase II clinical trial. Eligible pts include those with previously untreated metastatic CRC, adequate organ function and ECOG performance status 0–2. IRI (200 mg / m2) and A (7.5 mg / kg) were given on day 1, and XEL (1000 mg / m2 p.o. BID) was given on days 1–14 of every 21-day cycle. The dose of XEL was reduced to 750 mg / m2 BID for pts age ≥ 65. The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate, time to progression, overall survival and toxicity. Results: 50 pts (ECOG PS 0:1 = 27:23; male:female= 34:16) were enrolled over 19 months. Median age was 58 (range: 35–72). 7 pts had prior adjuvant chemotherapy. A total of 360 cycles were administered, with a median of 6 (range: 1–16). To date, 20 confirmed PR, 3 unconfirmed PR, and 20 SD by RECIST criteria were observed (ORR= 40%, disease control rate 86%). The median PFS was 11.1 months (95% CI: 9.2 months - not reached), and the 1-year progression-free rate was 49%. 7 pts have gone on to have metastatectomy. The most frequently reported related grade 3 or 4 adverse events were neutropenia (6), hand-foot syndrome (6), and diarrhea (5). One death was seen on study, and 1 pt had treatment-emergent grade 3 hypertension. Conclusions: XELIRI-A at doses studied appears to be well- tolerated. Results are favorable compared to those from previous studies. XELIRI-A at reduced doses is safe and effective as first-line treatment for mCRC. [Table: see text]

Multicenter Phase II Study of Bendamustine Plus Rituximab in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

2013 ◽  
Vol 31 (17) ◽  
pp. 2103-2109 ◽  
Author(s):  
Ken Ohmachi ◽  
Nozomi Niitsu ◽  
Toshiki Uchida ◽  
Seok Jin Kim ◽  
Kiyoshi Ando ◽  
...  
Keyword(s):  
B Cell ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Salvage Regimen ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Purpose Effective and less aggressive therapies are required for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for or have undergone autologous stem-cell transplantation (ASCT). The present phase II study assessed the efficacy and safety of bendamustine plus rituximab (BR) in this population. Patients and Methods Patients with relapsed or refractory DLBCL treated with one to three prior chemotherapy regimens received rituximab 375 mg/m2 intravenous (IV) infusion on day 1 and bendamustine 120 mg/m2 by IV infusion on days 2 and 3 of each 21-day cycle for up to six cycles. The primary end point was overall response rate (ORR), and the secondary end points were complete response (CR) rate, progression-free survival (PFS), and safety. Results Sixty-three patients were enrolled, and 59 received BR. The median age was 67 years (range, 36 to 75 years), and 62.7% of patients were 65 years of age or older. Fifty-seven patients (96.6%) were previously treated with rituximab-containing chemotherapy. The ORR was 62.7% (95% CI, 49.1% to 75.0%), with a CR rate of 37.3% (95% CI, 25.0% to 50.9%). The ORRs were comparable between patients ≥ 65 years of age and less than 65 years (62.2% and 63.6%, respectively). The median PFS was 6.7 months (95% CI, 3.6 to 13.7 months). The most frequently observed grade 3 or 4 adverse events were hematologic: lymphopenia (78.0%), neutropenia (76.3%), leukopenia (72.9%), CD4 lymphopenia (66.1%), and thrombocytopenia (22.0%). Conclusion BR is a promising salvage regimen for patients with relapsed or refractory DLBCL after rituximab-containing chemotherapy, warranting further investigation.

Phase II Study of 2-Weekly CHOP+Rituximab Followed by Yttrium 90 Ibritumomab Tiuxetan (Zevalin) in Patients with Previously Untreated Diffuse Large B Cell Lymphoma (DLBCL).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4507-4507 ◽  
Author(s):  
Parameswaran Venugopal ◽  
Stephanie A. Gregory ◽  
Teresa Obrien ◽  
Ray Drasga ◽  
Robert Bayer
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Stage Iv ◽  
B Cell Lymphoma ◽  
Cell Transplant ◽  
Ecog Performance Status ◽  
Stage Iv Disease ◽  
Liver And Kidney ◽  
Grade 3 ◽  
And Performance

Abstract Interval reduction from 3 to 2 weeks (CHOP-14; Pfreundschuh et al, Blood, 2004), addition of Rituximab to CHOP-21 (R-CHOP-21, Coiffier et al NEJM 2002) and consolidation with radioimmunotherapy following CHOP chemotherapy have all been shown to improve the outcome of DLBCL. We report the results of a Phase II clinical trial designed to evaluate the safety and efficacy of combination of the above, using 2-weekly CHOP+Rituximab followed by consolidation with Zevalin in patients with untreated DLBCL. Patients and Methods: Patients with previously untreated DLBCL with measurable disease, age>18 years and performance status 0-2 were eligible. Patients were required to have adequate marrow, liver and kidney functions. Patients with transformed lymphoma were excluded. Patients received standard CHOP along with Rituximab 375mg/m2 IV on day 1. Treatment was repeated every two weeks for a total of 6 cycles. Zevalin was administered within 6–8 weeks after the last dose of CHOPR therapy. Results: 14 patients were enrolled. The median age was 59.5 years (range 48–82), and 6 patients were men. All patients had an ECOG performance status of 0 or 1. 3 (21%) had stage II, 5 (36%) stage III and 6 (43%) had stage IV disease. IPI was 2 in 13 (93%) and 3 in 1 (7%). Bone marrow showed lymphoma in two patients only. LDH was elevated in 9 patients. All patients except 2 completed all 6 cycles of CHOP+R. One patient withdrew consent after 5 cycles and one patient with multiple lung masses could not be continued on therapy after two cycles because of prolonged rehab. Following CHOP+R alone in patients who received a minimum of 4 cycles of CHOP+R (13), 8 patients achieved CR and 5 achieved PR. Following consolidation with Zevalin, three patients in PR were converted to CR. After a median follow-up of 17.5 months, OSS is 14/14 (100%). 11 patients (79%) remain in CR. One patient progressed and proceeded to stem cell transplant; one came off study after 2 cycles of CHOP+R and remains with evidence of disease; and the third patient, who achieved PR with CHOP+R is waiting restaging after Zevalin. Most common adverse events were hematologic. Grade 3 Neutropenia was observed in 10 patients and grade 4 in 7. Grade 3 thrombocytopenia was observed in 3 and grade 4 in 1. Non-hematologic toxicities included: grade 3 pneumonia in 3, DVT in 1, grade 4 pneumonia in 1, grade 3 fever in 2 and grade 4 fever in 1. Conclusion: Consolidation with Zevalin radioimmunotherapy following dose dense CHOP+R therapy is well tolerated, effective and able to convert PRs to CRs.

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