Clinical activity and safety of antiprogrammed death-1 (PD-1) (BMS-936558/MDX-1106/ONO-4538) in patients (pts) with previously treated, metastatic renal cell carcinoma (mRCC): An updated analysis.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 351-351 ◽  
Author(s):  
David F. McDermott ◽  
Charles G. Drake ◽  
Mario Sznol ◽  
Toni K. Choueiri ◽  
John D. Powderly ◽  
...  
Keyword(s):  
Performance Status ◽  
Human Monoclonal Antibody ◽  
Antiangiogenic Therapy ◽  
Complete Response ◽  
Clinical Activity ◽  
Response Patterns ◽  
Ecog Performance Status ◽  
Activated T Cells ◽  
Initial Portion ◽  
Previously Treated

351 Background: BMS-936558 is a fully human monoclonal antibody that blocks the PD-1 coinhibitory receptor expressed by activated T cells. In the initial portion of a phase I study (CA209-003), BMS-936558 showed promising activity in pts with various solid tumors, including mRCC. Accrual was expanded to better characterize antitumor, safety, and dose effects. Methods: Pts with RCC were treated with BMS-936558 IV q2wk at 10 mg/kg initially, followed by additional pts at 1 mg/kg. Pts received up to 12 cycles (4 doses/cycle) of treatment or until unacceptable toxicity, confirmed progressive disease, or complete response (CR). Clinical activity was assessed by RECIST v1.0. Results: As of July 3, 2012, 34 mRCC pts had been treated at 1 mg/kg (n=18) or 10 mg/kg (n=16). ECOG performance status was 0 in 13 pts and 1 in 21 pts. More than 40% of study patients received ≥3 prior therapies, >70% received prior antiangiogenic therapy, and >50% received prior immunotherapy. Sites of metastatic disease included lung (n=30), lymph node (n=28), bone (n=10), and liver (n=9). The incidence of grade 3-4 related adverse events was 21% and included hypophosphatemia (6%) and respiratory disorders (6%); there were no drug-related deaths among mRCC pts. Ongoing durable clinical responses were observed at both 1 and 10 mg/kg doses (Table) with some continuing off treatment. Three pts demonstrated nonconventional response patterns and were not categorized as responders by conventional RECIST. Current median duration of response was 12.9 months for both 1 and 10 mg/kg doses. Conclusions: BMS-936558 is tolerable and exhibits ongoing durable clinical activity in pts with previously treated mRCC. Clinical trial information: NCT00730639. [Table: see text]

Clinical activity and safety of anti-PD-1 (BMS-936558, MDX-1106) in patients with previously treated metastatic renal cell carcinoma (mRCC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4505-4505 ◽  
Author(s):  
David F. McDermott ◽  
Charles G. Drake ◽  
Mario Sznol ◽  
Toni K. Choueiri ◽  
John Powderly ◽  
...  
Keyword(s):  
Performance Status ◽  
Human Monoclonal Antibody ◽  
Antiangiogenic Therapy ◽  
Progression Free Survival ◽  
Tumor Burden ◽  
Clinical Activity ◽  
Ecog Performance Status ◽  
Activated T Cells ◽  
Initial Portion ◽  
Previously Treated

4505 Background: BMS-936558 is a fully human monoclonal antibody that blocks the programmed death-1 co-inhibitory receptor (PD-1) expressed by activated T cells. In the initial portion of a phase I study, BMS-936558 showed promising activity in patients (pts) with various solid tumors, including mRCC. We expanded accrual in order to better characterize antitumor and dose effects. Methods: RCC pts were treated with BMS-936558 administered IV Q2WK at 10 mg/kg initially, followed by additional pts at 1 mg/kg. Pts received up to 12 cycles (4 doses/cycle) of treatment or until PD or CR. Clinical activity was assessed by RECIST 1.0. Results: Of 240 pts treated as of July 1 2011, 33 had mRCC and were treated at 1 (n=17) or 10 mg/kg (n=16). ECOG performance status was 0/1 in 13/19 pts. The number of prior therapies was 1 (n=10), 2 (n=9), or ≥3 (n=14), and included prior immunotherapy (n=20) or antiangiogenic therapy (n=24); 31 pts had prior nephrectomy. Sites of metastatic disease included lymph node (n=26), liver (n=7), lung (n=28), and bone (n=10). Median duration of therapy was 19 wk (max 96 wk). The incidence of grade 3-4 related AEs was 12% and included hypophosphatemia (6%), elevated ALT (3%), and cough (3%). Clinical activity was observed at both dose levels (Table). Some pts had a persistent reduction in overall tumor burden in the presence of new lesions and were not categorized as responders. Responses were noted in pts with visceral and bone metastases. Among the responders who were first treated ≥1 yr prior to data lock, 4 of 5 pts treated at 10 mg/kg had OR duration ≥1 yr, and 1 of 2 pts treated at 1 mg/kg was still on study with OR duration of 17.5 mo. Although the data for pts treated at 1mg/kg are not mature, the estimated progression-free survival (PFS) rate at 24 wk in pts receiving 10 mg/kg was 67% (Table). Conclusions: BMS-936558 is well tolerated and has durable clinical activity in pts with previously treated mRCC. Further development of BMS-936558 in pts with mRCC is ongoing. [Table: see text]

Clinical activity and safety of anti-PD-1 (BMS-936558, MDX-1106) in patients with advanced melanoma (MEL).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8507-8507 ◽  
Author(s):  
F. Stephen Hodi ◽  
Mario Sznol ◽  
David F. McDermott ◽  
Richard D. Carvajal ◽  
Donald P. Lawrence ◽  
...  
Keyword(s):  
Performance Status ◽  
Tumor Burden ◽  
Clinical Activity ◽  
Ecog Performance Status ◽  
Activated T Cells ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Previously Treated ◽  
Grade 3 ◽  
Dose Levels

8507 Background: BMS-936558 is a fully human mAb that blocks the programmed death-1 (PD-1) co-inhibitory receptor expressed by activated T cells. This study describes the activity and safety of BMS-936558 in patients (pts) with previously treated advanced MEL and underscores the importance of the PD-1/PD-L1 pathway in MEL therapy. Methods: BMS-936558 was administered IV Q2WK to pts with various solid tumors at doses of 0.1 to 10 mg/kg during dose-escalation and/or cohort expansion. Pts received up to 12 cycles (4 doses/cycle) of treatment or until PD or CR. Clinical activity was assessed by RECIST 1.0. Results: Of 240 pts treated as of July 1, 2011, 95 MEL pts were treated with BMS-936558 at 0.1 (n=13), 0.3 (n=17), 1 (n=28), 3 (n=17), or 10 mg/kg (n=20). ECOG performance status was 0/1/2 in 56/36/3 pts. The majority of pts (60/95) had received prior immunotherapy (IT), primarily interferon-alpha or IL-2 (prior anti-CTLA-4 excluded). Prior B-raf inhibitor therapy was noted in 7/95 pts. The number of prior therapies was 1 (n=35), 2 (n=34), or ≥3 (n=26). Sites of metastatic disease included lymph node (n=60), liver (n=32), lung (n=55), and bone (n=10). Median duration of therapy was 15 wk (max 120 wk), with 40 pts still receiving treatment. The incidence of grade 3-4 related AEs was 19% and included gastrointestinal (4%), endocrine (2%), and hepatobiliary disorders (1%). There were no drug-related deaths in MEL pts. Clinical activity was observed at all dose levels (Table). Of 20 pts with OR at the time of data lock, 12 had OR duration ≥1 yr and 6 pts were on study with OR duration between 1.9 and 11.3 mo. OR were seen in pts with visceral or bone metastases. Several pts had prolonged SD. Some had a persistent decrease in overall tumor burden in the presence of new lesions and were not categorized as responders. Conclusions: BMS-936558 had durable clinical benefit in pts with advanced MEL, including those who had received prior IT. Further development of BMS-936558 in MEL is ongoing. [Table: see text]

Clinical activity and safety of anti-PD1 (BMS-936558, MDX-1106) in patients with advanced non-small-cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7509-7509 ◽  
Author(s):  
Julie R. Brahmer ◽  
Leora Horn ◽  
Scott Antonia ◽  
David R. Spigel ◽  
Leena Gandhi ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Response Duration ◽  
Tumor Burden ◽  
Clinical Activity ◽  
Ecog Performance Status ◽  
Activated T Cells ◽  
Platinum Based Chemotherapy ◽  
Previously Treated

7509 Background: BMS-936558 is a fully human mAb that blocks the programmed death-1 (PD-1) co-inhibitory receptor expressed by activated T cells. We report here that BMS-936558 mediates antitumor activity in heavily pretreated patients (pts) with advanced NSCLC, a tumor historically not considered to be responsive to immunotherapy. Methods: BMS-936558 was administered IV Q2WK to pts with various solid tumors, including NSCLC, at doses of 0.1 to 10 mg/kg during dose-escalation and/or cohort expansion. Pts with advanced NSCLC previously treated with at least 1 prior chemotherapy regimen were eligible. Pts received up to 12 cycles (4 doses/cycle) of treatment or until PD or CR. Clinical activity was assessed by RECIST 1.0. Results: Of 240 pts treated as of July 1, 2011, 75 NSCLC pts were treated at 1 (n=17), 3 (n= 19), or 10 mg/kg (n=39). ECOG performance status was 0/1/2 in 24/49/2 pts. Tumor histology was squamous (n=17), non-squamous (n=52), or unknown (n=6). The number of prior therapies was 1 (n=9), 2 (n=20), ≥3 (n=45), or unknown (n=1). Ninety-five percent of pts had received platinum-based chemotherapy and 40% had a prior tyrosine kinase inhibitor. Sites of metastatic disease included lymph node (n=50), liver (n=12), lung (n=62), and bone (n=13). Median duration of therapy was 10 wk (max 100 wk). Common related AEs were fatigue (17%), nausea (11%), pyrexia (7%), pruritus (7%), dizziness (7%), and anemia (7%). The incidence of grade 3-4 related AEs was 8%. There was 1 drug-related death due to pulmonary toxicity. Clinical activity was observed at all dose levels (Table) and in multiple histologies. Several pts had prolonged SD. Some had a persistent decrease in overall tumor burden in the presence of new lesions and were not categorized as responders. At the time of data lock, of 10 OR pts, 3 had responses lasting ≥6 mo and 5 were on study with response duration of 1.8-5.5 mo. Conclusions: BMS-936558 is well tolerated and has encouraging clinical activity in pts with previously treated advanced NSCLC. Further development of BMS-936558 in pts with advanced NSCLC is warranted. [Table: see text]

Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-mutated metastatic non-small cell lung cancer (NSCLC): Interim results of DESTINY-Lung01.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9504-9504 ◽  
Author(s):  
Egbert F. Smit ◽  
Kazuhiko Nakagawa ◽  
Misako Nagasaka ◽  
Enriqueta Felip ◽  
Yasushi Goto ◽  
...  
Keyword(s):  
Topoisomerase I ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Clinical Activity ◽  
Antibody Drug Conjugate ◽  
Ecog Performance Status ◽  
Platinum Based Chemotherapy ◽  
Grade 3

9504 Background: T-DXd is an antibody-drug conjugate composed of an anti-HER2 antibody, cleavable tetrapeptide-based linker, and topoisomerase I inhibitor payload. In a phase I trial, patients (pts) with HER2-mutated NSCLC who received T-DXd had a confirmed objective response rate (ORR) of 72.7% (8/11) (Tsurutani et al, WCLC 2018). DESTINY-Lung01 (NCT03505710) is an ongoing, multicenter, phase II study of T-DXd in pts with non-squamous NSCLC overexpressing HER2 or containing a HER2-activating mutation. We report data for the cohort with HER2 mutations after a median follow-up of 8.0 mo (range, 1.4-14.2 mo). Methods: Pts were treated with T-DXd 6.4 mg/kg every 3 weeks. The primary endpoint was confirmed ORR (complete response [CR] + partial response [PR]) by ICR. Additional endpoints were disease control rate (DCR; CR + PR + stable disease), duration of response (DOR), progression-free survival (PFS), and safety. Results: At data cutoff (25 Nov 2019), 42 pts (64.3% female) had received T-DXd. Median age was 63.0 years (range, 34-83 years; < 65 y, 59.5%); 45.2% had central nervous system metastases; ECOG performance status was 0 in 23.8% of pts and 1 in 76.2%. HER2 mutations were predominantly in the kinase domain (90.5%). Most pts (90.5%) had prior platinum-based chemotherapy and 54.8% had anti–PD-1 or –PD-L1 treatment; median number of prior treatment lines was 2 (range, 1-6). Median treatment duration was 7.75 mo (range, 0.7-14.3 mo); 45.2% of pts remained on treatment. Confirmed ORR by ICR among the 42 pts was 61.9% (95% CI, 45.6%-76.4%); median DOR was not reached at data cutoff; 16 of 26 responders remained on treatment at data cutoff; DCR was 90.5% (95% CI, 77.4%-97.3%); estimated median PFS was 14.0 mo (95% CI, 6.4-14.0 mo). All pts (42/42) had treatment-emergent adverse events (TEAEs); 64.3% were grade ≥ 3 (52.4% drug-related), including decreased neutrophil count (26.2%) and anemia (16.7%). There were 5 cases (11.9%) of drug-related interstitial lung disease (ILD) as adjudicated by an independent committee (all grade 2, no grade ≥ 3) and 1 case of grade 1 ILD is pending adjudication. TEAEs led to dose interruption in 25 pts (59.5%), dose reduction in 16 pts (38.1%), and treatment discontinuation in 10 pts (23.8%). Conclusions: T-DXd demonstrated promising clinical activity with high ORR and durable responses in pts with HER2-mutated NSCLC. The safety profile was generally consistent with previously reported studies. Clinical trial information: NCT03505710 .

Randomized phase II study of erlotinib alone and in combination with bortezomib in previously treated advanced non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7680-7680 ◽  
Author(s):  
T. J. Lynch ◽  
D. W. Fenton ◽  
V. Hirsh ◽  
D. J. Bodkin ◽  
E. Middleman ◽  
...  
Keyword(s):  
Egf Receptor ◽  
Performance Status ◽  
Treatment Options ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Ecog Performance Status ◽  
Combination Methods ◽  
Previously Treated ◽  
Grade 3

7680 Background: Treatment options for previously treated NSCLC are limited, warranting consideration of novel combinations. This study evaluated the activity and toxicity of erlotinib with bortezomib, a proteasome inhibitor. Dosing was based on the approved indication for erlotinib and on phase I data for the combination. Methods: Patients (pts) with Stage IIIB/IV NSCLC who progressed following one prior line of chemotherapy, with no prior exposure to an EGF-receptor inhibitor and ECOG performance status 0 or 1 were randomly assigned to erlotinib 150 mg po daily alone (arm A) or in combination with bortezomib 1.6 mg/m2 iv on days 1 and 8 (arm B) of a 21-day cycle. Response was evaluated by RECIST and toxicity was graded using NCI CTCAE 3.0. A Simon optimal two-stage design was used to evaluate anti-tumor activity in response-evaluable pts. Results: Fifty pts were treated at 17 sites (January-June 2006); baseline characteristics and treatment intensity were comparable in both arms. Among 24 response-evaluable pts in each arm, there were 3 partial responses (PR) and 1 complete response in arm A and 2 PR in arm B. Median progression-free survival (PFS) was 2.7 and 1.4 months in arms A and B, respectively. The study was halted as required at the planned interim analysis due to insufficient clinical activity in arm B. Activity and toxicity in arm A were consistent with published reports for erlotinib alone. Adverse-event profiles were as expected in both arms, with no significant additivity. In arm B, one pt died of pneumonia. The most common grade 3 treatment-related toxicity was skin rash (12% arm A and 8% arm B), and rash severity correlated with PFS: grades 2/3, 2.8 months PFS (20 pts); grades 0/1, 1.4 months PFS (28 pts), p=0.032. In arm B, one pt each had grade 3 anorexia, hypokalemia, and worsened peripheral sensory neuropathy compared with baseline. There were no grade 4 treatment related toxicities in either arm. Conclusions: The combination of erlotinib and bortezomib in the doses and schedules used in this trial was well tolerated but did not show sufficient activity at this dose and schedule to warrant further development. No significant financial relationships to disclose.

Phase I dose escalation trial of tremelimumab (CP-675,206) administered in combination with PF-3512676 in patients with melanoma or other advanced cancers

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 3046-3046
Author(s):  
C. Underhill ◽  
M. Millward ◽  
S. Lobb ◽  
J. McBurnie ◽  
S. Meech ◽  
...  
Keyword(s):  
Dose Level ◽  
Advanced Cancer ◽  
Performance Status ◽  
Human Monoclonal Antibody ◽  
Advanced Melanoma ◽  
Clinical Activity ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Level 3 ◽  
Level 2

3046 Background: Tremelimumab, a fully human monoclonal antibody specific for cytotoxic T-lymphocyte antigen 4 (CTLA4), and PF-3512676, an oligodeoxynucleotide toll-like receptor 9 agonist, are both novel, targeted immune modulators that can elicit durable antitumor responses in patients with advanced cancer. The tolerability of the combination of these two agents was investigated. Methods: Eligibility criteria included advanced melanoma or other advanced cancer, ECOG performance status of 0 or 1, and no history of autoimmune disease. Patients received intravenous tremelimumab (6.0, 10.0, or 15.0 mg/kg) every 12 weeks plus 0.05 mg/kg subcutaneous PF-3512676 weekly. Further escalation of PF-3512676 (to 0.1 mg/kg and 0.2 mg/kg) was planned once the MTD of tremelimumab had been determined. Primary endpoint was safety of the treatment combination; secondary endpoints included clinical activity, pharmacokinetics (PK), and immunologic measurements. Results: To date, 15 patients (melanoma, n = 12; mesothelioma, n = 2; prostate, n = 1) have been treated in this study: 3 at dose level 1 (6 mg/kg tremelimumab + 0.05 mg/kg PF-3512676); 6 at dose level 2 (10 mg/kg tremelimumab + 0.05 mg/kg PF-351276); and 6 at dose level 3 (15 mg/kg tremelimumab + 0.05 mg/kg PF-3512676). There were two DLTs at dose level 3: G3 diarrhea (n=1) and G3 nausea and vomiting associated with biopsy-proven duodenitis (n=1). One DLT, G3 hypophysitis, occurred at dose level 2. Patients with DLTs responded to corticosteroid therapy. Common adverse events included mild to moderate PF-3512676 injection site reactions (n=14), mild to moderate flu-like symptoms (n=9), G1/2 diarrhea (n=9), and G1/2 nausea (n=8). Presently, there are 2 PRs (13%) and 5 SDs among the 15 patients. Updated safety, efficacy, and PK data will be reported. Conclusions: At dose levels tested to date, the combination of tremelimumab and PF-3512676 has been tolerable and showed evidence of antitumor activity in patients with advanced melanoma. The MTD for this combination has yet to be determined, and a fourth intermediate dose level (10 mg/kg tremelimumab + 0.1 mg/kg PF-3512676) is currently being explored. [Table: see text]

A multicenter phase II study of cisplatin (C), gemcitabine (G), and bevacizumab (B) as first-line chemotherapy for metastatic urothelial carcinoma (UC): Hoosier Oncology Group GU-0475

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5018-5018
Author(s):  
N. M. Hahn ◽  
W. M. Stadler ◽  
R. T. Zon ◽  
D. M. Waterhouse ◽  
J. Picus ◽  
...  
Keyword(s):  
Performance Status ◽  
Progression Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
Clinical Activity ◽  
Hematologic Toxicity ◽  
First Line ◽  
Ecog Performance Status ◽  
Angiogenic Therapy ◽  
Grade 3

5018 Background: Despite CG therapy, most metastatic UC patients die from their disease. Novel approaches are needed. Combining anti-angiogenic therapy with chemotherapy has improved outcomes in other malignancies, offering hope for similar improvements in UC patients. Methods: Metastatic or unresectable chemonaive UC patients (pts) with an ECOG performance status of 0–1 received C 70 mg/m2 iv d1, G 1,000–1,250 mg/m2 iv d1, 8, and B 15 mg/kg iv d1 on a q21d cycle for up to 8 cycles. Gemcitabine was reduced to 1,000 mg/m2 iv d1, 8 for all subsequent pts after 7 thromboembolic events were noted in the first 17 pts. The primary endpoint was progression free survival (PFS). The trial was designed to detect a 33% improvement in PFS from 7.5 months with traditional CG therapy to 11.25 months with CGB. Results: By December 2008, 45 pts were enrolled, with 43 evaluable for toxicity, 36 for response. Demographics include: 33 (77%) male, 10 (23%) female; median age 66 (Range: 41 - 78); 26 (60%) and 17 (40%) ECOG 0/1; 19 (44%) and 24 (56%) lymph node only / visceral metastases. PFS will be evaluated in May 2009 when all pts will have more than 6 month follow-up data. 14 (33%) and 6 (14%) pts experienced grade 3 or 4 hematologic toxicity (4 pts - thrombocytopenia, 2 pts - neutropenic fever). Grade 3 or 4 nonhematologic toxicity was observed in 24 (56%) and 9 (21%) pts (DVT/PE - 9 pts, CNS hemorrhage/proteinuria/hypertension - 1 pt each) Best RECIST response was: complete response 6 pts (17%, 95% CI 6–33%), partial response 18 pts (50%, 95% CI 33–67%); with overall response rate of 67% (95% CI 51–82%). Stable disease lasting at least 12 weeks was observed in 10 pts (28%, 95% CI 14–45%) and progressive disease in 2 pts (5%, 95% CI 1–19%). Conclusions: CGB demonstrates significant clinical activity in the first-line treatment of metastatic UC patients at the expense of considerable toxicity. The durability of disease control will be determined by assessment of PFS. A phase III trial to further define the toxicity risk vs. clinical benefit of bevacizumab addition to platinum-based doublets is planned in this population. [Table: see text]

scholarly journals TROG 18.01 phase III randomised clinical trial of the Novel Integration of New prostate radiation schedules with adJuvant Androgen deprivation: NINJA study protocol

BMJ Open ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. e030731 ◽  
Author(s):  
Jarad Martin ◽  
Paul Keall ◽  
Shankar Siva ◽  
Peter Greer ◽  
David Christie ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Controlled Trial ◽  
Performance Status ◽  
Androgen Deprivation ◽  
Phase Iii ◽  
High Dose ◽  
The Novel ◽  
Ecog Performance Status ◽  
Initial Portion ◽  
The Impact

IntroductionStereotactic body radiotherapy (SBRT) is a non-invasive alternative to surgery for the treatment of non-metastatic prostate cancer (PC). The objectives of the Novel Integration ofNew prostate radiation schedules with adJuvant Androgen deprivation (NINJA) clinical trial are to compare two emerging SBRT regimens for efficacy with technical substudies focussing on MRI only planning and the use of knowledge-based planning (KBP) to assess radiotherapy plan quality.Methods and analysisEligible patients must have biopsy-proven unfavourable intermediate or favourable high-risk PC, have an Eastern Collaborative Oncology Group (ECOG) performance status 0-1 and provide written informed consent. All patients will receive 6 months in total of androgen deprivation therapy. Patients will be randomised to one of two SBRT regimens. The first will be 40 Gy in five fractions given on alternating days (SBRT monotherapy). The second will be 20 Gy in two fractions given 1 week apart followed 2 weeks later by 36 Gy in 12 fractions given five times per week (virtual high-dose rate boost (HDRB)). The primary efficacy outcome will be biochemical clinical control at 5 years. Secondary endpoints for the initial portion of NINJA look at the transition of centres towards MRI only planning and the impact of KBP on real-time (RT) plan assessment. The first 150 men will demonstrate accrual feasibility as well as addressing the KBP and MRI planning aims, prior to proceeding with total accrual to 472 patients as a phase III randomised controlled trial.Ethics and disseminationNINJA is a multicentre cooperative clinical trial comparing two SBRT regimens for men with PC. It builds on promising results from several single-armed studies, and explores radiation dose escalation in the Virtual HDRB arm. The initial component includes novel technical elements, and will form an important platform set for a definitive phase III study.Trial registration numberANZCTN 12615000223538.

Rituximab® and High Dose Methylprednisolone (HDMP) for the Treatment of Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2518-2518
Author(s):  
Januario E. Castro ◽  
Jan Bole ◽  
Carlos E. Prada ◽  
Thomas J. Kipps
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Performance Status ◽  
Variable Region ◽  
Response Assessment ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Ecog Performance Status ◽  
Female Ratio ◽  
High Dose Methylprednisolone

Abstract High-dose gluocorticoids and the anti-CD20 mAb Rituximab each can effect partial responses in patients with chronic lymphocytic leukemia (CLL), although complete and durable responses to treatment with either of these agents have not been reported. We examined whether patients with relapsed and/or refractory CLL could respond to these agents when used in combination in a pilot clinical trial. Fourteen patients with progressive, symptomatic, and relapsed/refractory disease were treated with three four-week cycles of high-dose Methylprednisolone (HDMP) at 1gr/m2 daily for 5 days and weekly Rituximab® at 375mg/m2 for four weeks. The median age of the patients was 60 years, the male to female ratio was 4:1, the ECOG performance status was &lt; 2, and the average number of prior treatments was 2. All patients failed or were intolerant to fludarabine and 86% had high-risk disease by the modified Rai classification. Sixty-five percent of the patients had CLL cells that expressed ZAP-70 and unmutated immunoglobulin variable region genes. Response assessment was performed at the end of each cycle, two months after completion of treatment, and each 3–6 months thereafter until the patients experienced disease progression and/or required further treatment. Objective responses were observed in all 14 patients, with 6 patients achieving a complete response (CR) and the remainder a partial response (PR) as per the NCI-working group criteria. We observed a significant decrease in peripheral white blood cell (WBC) counts, increase in hemoglobin, elevation of platelet counts and a dramatic decrease in lymphadenopathy and splenomegaly. Five of the treated patients have not required further treatment with a median follow up of 26 months. Of these 5 patients 3 have maintain a CR. The median time to progression (TTP) was 12 months. Overall, the treatment was well tolerated and all the patients, except one, completed 3 cycles of therapy. The majority of adverse events were Grade I-II (fluid retention, cough, transient hyperglycemia, fatigue). In addition, we observed 7 episodes of grade III-IV toxicity secondary to (anemia, CMV esophagitis and GI bleeding with one case each and two cases each of thrombocytopenia and neutropenia). These data suggest that treatment with the combination of Rituximab® and HDMP has increased activity over treatment with either agent alone and may produce durable complete responses in patients with refractory and / or relapsed CLL.

Activity of Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin®) in 22 Patients with Relapsed and Refractory Mantle Cell Lymphoma (MCL).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2452-2452 ◽  
Author(s):  
Anas Younes ◽  
Barbara Pro ◽  
Maria A. Rodriguez ◽  
Jorge E. Romaguera ◽  
Peter McLaughlin ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
Performance Status ◽  
B Cell Lymphoma ◽  
Cns Lymphoma ◽  
Ibritumomab Tiuxetan ◽  
Ecog Performance Status ◽  
Bulky Disease ◽  
Platelet Counts ◽  
Previously Treated ◽  
Yttrium 90

Abstract Background: The management of MCL is a significant therapeutic challenge, especially in patients with relapsed or refractory disease, who are generally refractory to salvage chemotherapy. Although recent studies have shown the clinical utility of radioimmunotherapy (RIT) in relapsed and transformed indolent B-cell lymphoma, the clinical efficacy of this treatment modality in patients with MCL is unknown. We report the results of an ongoing phase II clinical trial of yttrium 90 ibritumomab tiuxetan (Zevalin®) in patients with relapsed and refractory MCL. Patients and Methods: Patients with relapsed or refractory MCL with measurable disease, age ≥18 years, and performance status &lt;3 were eligible. Patients were required to have adequate function of the bone marrow (ANC ≥1,500/mm3, platelets ≥100,000/mm3), liver, and kidneys. Patients were excluded if they had prior stem cell transplantation, RIT, CNS lymphoma, HIV infection, pleural effusion, HAMA reactivity, or circulating lymphoma cell count &gt;5000/mm3. Patients with pretreatment platelet counts ≥150,000/mm3 received a dose of Zevalin at 0.4 mCi 90Y/kg (maximum dose 32 mCi), whereas those with platelet counts &lt;150,000/mm3 received 0.3 mCi 90Y/kg. Results: Twenty-two patients were enrolled and all qualified for evaluation of treatment response and toxicity. The median age was 67 years (range 51–77), and 18 patients were male. All patients had an ECOG performance status of 0 or 1 and had been previously treated with rituximab with or without other chemotherapy. The median number of prior regimens was 3 (range 1–6). Fourteen patients were previously treated with Hyper-CVAD alternating with MTX/Ara-C, 21 previously received rituximab, and 5 previously received bortezomib. Zevalin treatment was generally well tolerated, with the most common toxicities being hematologic. Objective responses were observed in 8 of 22 patients (36%), including 3 CR and 2 CRu. Seven of the eight responding patients were previously treated with 3 or less treatment regimens, and all responding patients did not have bulky disease, with the largest lesion measuring 3 cm or less. Median time to progression for CR/CRu patients was 6 months. Conclusion: The observed responses to Zevalin in heavily pretreated patients with MCL are promising, but the duration of responses has been short. Furtherinvestigation is warranted after first or second relapse, and in conjunction with front-line therapy.

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